http://www.fhcrc.org/en/treatment/clinical-trials.html Clinical trials that are being conducted at the Fred Hutchinson Cancer Research Center, the University of Washington and Seattle Children's en-us Wed, 19 Jun 2013 00:15:01 GMT 720 388 Autologous Stem Cell Transplant Followed By Donor Stem Cell Transplant In Treating Patients With Relapsed or Refractory Lymphoma I/II David Maloney, MD, PhD 1409.00 36; 38; 48; 64 Hematologic Malignancies; Hodgkin's Lymphoma; Lymphoma; Non-Hodgkin's Lymphoma (NHL) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.388.html http://www.clinicaltrials.gov/ct/search?term=NCT00005803 NCT00005803 Purpose This phase I/II trial is studying how well giving autologous stem cell transplant followed by donor stem cell transplant works in treating patients with relapsed or refractory lymphoma. Peripheral blood stem cell transplant using stem cells from the patient or a donor may be able to replace immune cells that were destroyed by chemotherapy used to kill tumor cells. The donated stem cells may also help destroy any remaining cancer cells (graft-versus-tumor effect) Ages Eligible for Study: up to 75 Years Genders Eligible for Study: Both - Patients with lymphoma (non-Hodgkin lymphoma [NHL], chronic lymphocytic leukemia/small lymphocytic lymphoma [CLL/SLL] or Hodgkin lymphoma) with primary refractory or relapsed disease after standard chemotherapy at high risk of relapse with conventional autografting; patients with a diagnosis of CLL (or small lymphocytic lymphoma) or diagnosis of CLL that progresses to prolymphocytic leukemia (PLL), or T-cell CLL or PLL - Must have an HLA genotypically or phenotypically identical related donor or, at a minimum, a high likelihood of identifying an HLA-matched unrelated donor; the determination of availability of a suitable unrelated donor may be based on a World-Book search - Cross-over to other tandem autologous-allogeneic research protocol (#2241) will be allowed if the patient loses the suitable HLA-matched related or unrelated donor but has an available HLA-haploidentical donor before receiving the allogeneic transplantation and if the patient meets the eligibility criteria of the subsequent study - Cross-over from other tandem autologous-allogeneic research protocol (#2241) will be allowed if a suitable HLA-matched related or unrelated donor is identified before receiving the allogeneic transplantation and if the patient meets the eligibility criteria of the subsequent study - Signed informed consent - Detectable tumor on radiographic studies or bone marrow biopsy prior to mobilization regimen - Expected survival >= 3 months from study entry - DONOR: HLA genotypically or phenotypically identical related donor - DONOR: must consent to G-CSF administration and leukapheresis for both PBSC allograft and subsequent donor lymphocyte infusion (DLI) - DONOR: must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral or subclavian) - DONOR: Age < 75 yrs, older donors may be considered after review at Patient Care Conference - DONOR: Fred Hutchinson Cancer Research Center (FHCRC) matching allowed will be Grades 1.0 to 2.1; unrelated donors who are prospectively: Matched for HLA-A, B, C, DRB1 and DQB1 by high resolution typing; only a single allele disparity will be allowed for HLA-A, B, or C as defined by high resolution typing - DONOR: Donors are excluded when preexisting immunoreactivity is identified that would jeopardize donor hematopoietic cell engraftment; this determination is based on the standard practice of the individual institution; the recommended procedure for patients with 10 of 10 HLA allele level (phenotypic) match is to obtain a panel reactive antibody (PRA) screens to class I and class II antigens for all patients before HCT; if the PRA shows > 10% activity, then flow cytometric or B and T cell cytotoxic cross matches should be obtained; the donor should be excluded if any of the cytotoxic cross match assays are positive; for those patients with an HLA Class I allele mismatch, flow cytometric or B and T cell cytotoxic cross matches should be obtained regardless of the PRA results; a positive anti-donor cytotoxic crossmatch is an absolute donor exclusion - DONOR: patient and donor pairs homozygous at a mismatched allele in the graft rejection vector are considered a two-allele mismatch, i.e., the patient is A*0101 and the donor is A*0102, and this type of mismatch is not allowed - DONOR: Only G-CSF mobilized peripheral blood mononuclear cells (PBMC) only will be permitted as a hematopoietic stem cell (HSC) source on this protocol Other eligibility criteria may apply. - Life expectancy severely limited by disease other than lymphoma - Prior autologous hematopoietic stem cell transplant - Patients at high risk of veno-occlusive disease of the liver (criteria not yet rigorously defined but includes bilirubin > 2.0 mg and serum glutamic oxaloacetic transaminase [SGOT] or serum glutamic pyruvate transaminase [SGPT] > 2 x normal); patients may be accepted outside of this range if cleared by gastrointestinal (GI) consult - Cardiac ejection fraction (EF) < 40% on multi-gated acquisition (MUGA) scan or cardiac echo (or if unable to obtain ejection fraction, shortening fraction of < 26%); patients with active or a history of cardiac disease should be evaluated with appropriate cardiac studies and/or consult; ejection fraction is required if age > 50 years or there is a history of anthracyclines or history of cardiac disease; patients with a shortening fraction < 26% may be enrolled if approved by a cardiologist - Baseline serum-creatinine > 2.0 mg/dl and a calculated or measured creatinine clearance of < 50 ml/minute - Seropositive for the human immunodeficiency virus (HIV) - Pulmonary dysfunction as measured by a corrected diffusing capacity of the lung for carbon monoxide (DLCO) < 50% of predicted total lung capacity (TLC) < 30%, forced expiratory volume in 1 second (FEV1) < 30% and/or receiving supplementary continuous oxygen; the FHCRC primary investigator (PI) of the study must approve enrollment of all patients with pulmonary nodules - Pregnancy or breast-feeding - Radiation therapy to mediastinum within 3 months prior to enrollment - Patients with poorly controlled hypertension despite hypertensive medication - Karnofsky score < 60; pediatric criteria: Lansky Play-Performance Score < 40 - Patients with cluster of differentiation (CD)34 selected auto grafts - Patients with active non-hematologic malignancies (except nonmelanoma skin cancers); this exclusion does not apply to patients with non-hematologic malignancies that do not require therapy - Patients with a history of non-hematologic malignancies (except nonmelanoma skin cancers) currently in a complete remission, who are less than 5 years from the time of complete remission, and have a > 20% risk of disease recurrence; this exclusion does not apply to patients with non-hematologic malignancies that do not require therapy - DONOR: Identical twin - DONOR: Age less than 12 years - DONOR: Pregnancy - DONOR: HIV seropositivity - DONOR: Inability to achieve adequate venous access - DONOR: Known allergy to G-CSF - DONOR: Current serious systemic illness - DONOR: Failure to meet FHCRC criteria for stem cell donation - DONOR: Donor (or centers) who will exclusively donate marrow Other exclusion criteria may apply. 281d0ce28687bad8c0e670c96c6b75f1 390 Fludarabine and Total-Body Irradiation Followed By Donor Stem Cell Transplant and Cyclosporine and Mycophenolate Mofetil in Treating HIV-Positive Patients With or Without Cancer I Ann Woolfrey, MD 1410.00 11; 39; 50 Bone Marrow and Hematopoietic Stem Cell Transplant (BMT and HSCT); Immunodeficiency Syndromes; Malignancies in HIV Patients Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.390.html http://www.clinicaltrials.gov/ct/search?term=NCT00112593 NCT00112593 This clinical trial studies giving fludarabine and total-body irradiation (TBI) together followed by a donor stem cell transplant and cyclosporine and mycophenolate mofetil in treating human immunodeficiency virus (HIV)-positive patients with or without cancer. Giving low doses of chemotherapy, such as fludarabine, and TBI before a donor bone marrow or peripheral blood stem cell transplant helps stop the growth of cancer or abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine (CSP) and mycophenolate mofetil (MMF) after the transplant may stop this from happening Ages Eligible for Study: up to 75 Years Genders Eligible for Study: Both - Patients with hematologic malignancy, lymphoma or other HIV-associated malignancy are eligible provided these criteria are met: - The malignancy is in complete remission or very good partial remission, defined as a significant reduction of disease with therapy and no evidence for continued tumor growth in the case of lymphoma or solid tumors - highly active antiretroviral therapy (HAART) is initiated within one month of hematopoietic cell transplant - Viral load has decreased by >= 1.5 logs or viral load < 5000 copies/ml plasma on HAART therapy - CD4 count is allowed to be > 100 cells/ul - HIV infected patients without malignancy who have failed HAART are eligible provided that these criteria are met: - They have been treated with more than one regimen of HAART for a total of at least 6 months duration - The viral load is < 50 copies/ml plasma - The CD4 count < 100 cells/ul - DONOR: Human leukocyte antigen (HLA) genotypically/phenotypically identical donor; if more than one HLA-identical sibling is available, priority will be given to donors matched for cytomegalovirus (CMV) status, ABO titer, and sex Peripheral blood stem cells will be collected from donors greater than 12 years of age Bone marrow will be collected from donors less than 12 years of age - DONOR: HLA phenotypically identical unrelated donor; match grades allowed: Match grade 1: Matched at allele level for HLA-A, B, C, DRB1, and DQB1 Match grade 2.1: Single allele disparity for HLA-A, B, C, DRB1, and DQB1 Other eligibility criteria may apply. - Positive serology for toxoplasma gondii on treatment or with evidence of active infection - Patients with other disease or organ dysfunction that would limit survival to less than 30 days - Patients with medical history of noncompliance with HAART or medical therapy - DONOR: Donors for whom medical or psychologic reasons would make donor procedure intolerable - DONOR: Marrow donors who have increased anesthetic risk - DONOR: Donors who are HIV positive - DONOR: Age > 75 years Other exclusion criteria may apply. 6bd2e9fb245fb74abb4c0d6bd125708e 541 Fludarabine Phosphate and Total-Body Irradiation Followed By Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia or Chronic Myelogenous Leukemia That Has Responded to Treatment With Imatinib Mesylate, Dasatinib, or Nilotinib II George Georges, MD 1581.00 1; 11; 19; 36; 43 Acute Lymphoid Leukemia (ALL); Bone Marrow and Hematopoietic Stem Cell Transplant (BMT and HSCT); Chronic Myeloid Leukemia (CML); Hematologic Malignancies; Leukemia Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.541.html http://www.clinicaltrials.gov/ct/search?term=NCT00036738 NCT00036738 This phase II trial is studying how well fludarabine phosphate and total-body irradiation followed by donor peripheral blood stem cell transplant work in treating patients with acute lymphoblastic leukemia or chronic myelogenous leukemia that has responded to previous treatment with imatinib mesylate, dasatinib, or nilotinib. Giving low doses of chemotherapy, such as fludarabine phosphate, and total-body irradiation (TBI) before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving mycophenolate mofetil and cyclosporine after the transplant may stop this from happening Ages Eligible for Study: up to 70 Years Genders Eligible for Study: Both - Patients =< 12 years of age must be approved by Fred Hutchinson Cancer Research Center (FHCRC) principal investigator (PI) in advance - Patients with a history of Ph+ ALL or CML-BC who, after receiving imatinib mesylate, (or either dasatinib or nilotinib) have < 15% blasts on morphologic marrow evaluation; patients with no detectable Ph+ ALL by morphologic or molecular assays (complete remission) will be accepted - An appropriately human leukocyte antigen (HLA) matched related or unrelated donor must be prospectively identified who will be available to donate filgrastim (G-CSF) mobilized stem cells RELATED DONOR: - Related donor who is HLA genotypically identical at least at one haplotype and may be genotypically or phenotypically identical at the allele level at HLA-A, -B, -C, -DRB1, and -DQB1; - Donor must consent to G-CSR administration and leukapheresis; - Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral, subclavian) HLA-MATCHED UNRELATED DONOR: - FHCRC matching allowed will be Grades 1.0 to 2.1; Unrelated donors who are prospectively matched for HLA-A, B, C, DRB1 and DQB1 by high resolution typing; only a single allele disparity will be allowed for HLA-A, B, or C as defined by high resolution typing - A positive anti-donor cytotoxic crossmatch is an absolute donor exclusion; Donors are excluded when preexisting immunoreactivity is identified that would jeopardize donor hematopoietic cell engraftment; This determination is based on the standard practice of the individual institution; The recommended procedure for patients with 10 of 10 HLA allele level (phenotypic) match is to obtain a panel reactive antibody (PRA) screens to class I and class II antigens for all patients before HCT; If the PRA shows >10% activity, then flow cytometric or B and T cell cytotoxic cross matches should be obtained; The donor should be excluded if any of the cytotoxic cross match assays are positive; For those patients with an HLA Class I allele mismatch, flow cytometric or B and T cell cytotoxic cross matches should be obtained regardless of the PRA results - Patient and donor pairs homozygous at a mismatched allele in the graft rejection vector are considered a two-allele mismatch, i.e., the patient is A*0101 and the donor is A*0102, and this type of mismatch is not allowed - Only G-CSF mobilized PBSC only will be permitted as a HSC source on this protocol Other eligibility criteria may apply. - Central nervous system (CNS) involvement with leukemia refractory to intrathecal chemotherapy; prior to HSCT (all patients must receive a diagnostic lumbar puncture (LP) with intrathecal (IT) chemotherapy as per standard practice) - Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment - Patients with active non-hematologic malignancies (except non-melanoma skin cancers); this exclusion does not apply to patients with non-hematologic malignancies that do not require therapy - Patients with a history of non-hematologic malignancies (except non-melanoma skin cancers) currently in a complete remission, who are less than 5 years from the time of complete remission, and have a > 20% risk of disease recurrence; this exclusion does not apply to patients with non-hematologic malignancies that do not require therapy - Females who are pregnant or breastfeeding - Patients who are human immunodeficiency virus (HIV)-positive - Patients with poorly controlled hypertension despite multiple antihypertensives - Adults: Karnofsky score < 60 - Pediatrics: Lansky Play-Performance Score < 40 - Patients with cardiac ejection fraction < 35% (or, if unable to obtain ejection fraction, shortening fraction of < 26%); ejection fraction is required if age > 50 years or there is a history of anthracycline exposure or history of cardiac disease; patients with a shortening fraction < 26% may be enrolled if approved by a cardiologist - Diffusing capacity of the lungs for carbon monoxide (DLCO) < 30% - Total lung capacity (TLC) < 30% - Forced expiratory volume in one second (FEV1) < 30% and/or receiving supplementary continuous oxygen; the FHCRC PI of the study must approve enrollment of all patients with pulmonary nodules - Patients with clinical or laboratory evidence of liver disease would be evaluated for the cause of liver disease, its clinical severity in terms of liver function, and the degree of portal hypertension; patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, or symptomatic biliary disease - Creatinine levels more than 2.2 X's the upper limit of normal (ULN) at the laboratory where the analysis was performed - Patients with active bacterial or fungal infections unresponsive to medical therapy - For patients receiving dasatinib or nilotinib, baseline QTc (Fridericia's method) prolongation greater than 500 msec RELATED DONORS: - Identical twin - Infection with HIV - Inability to achieve adequate venous access; - Known allergy to G-CSF - Current serious system illness - Bone marrow (BM) donors HLA-MATCHED UNRELATED DONORS: - BM donors - Donors who are HIV-positive and/or, medical conditions that would result in increased risk for G-CSF mobilization and harvest of PBSC Other exclusion criteria may apply. ecbb943a194062f6455a2dfc02c01c35 2271 Iodine I 131 Monoclonal Antibody BC8, Fludarabine Phosphate, Total Body Irradiation, and Donor Stem Cell Transplant Followed By Cyclosporine and Mycophenolate Mofetil in Treating Patients With Advanced Acute Myeloid Leukemia or Myelodysplastic Syndrome II John Pagel, MD, PhD 1809.00 2; 11; 36; 43; 61 Acute Myeloid Leukemia (AML); Bone Marrow and Hematopoietic Stem Cell Transplant (BMT and HSCT); Hematologic Malignancies; Leukemia; Myelodysplastic and Myeloproliferative Syndromes (MDS and MPD) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.2271.html http://www.clinicaltrials.gov/ct/search?term=NCT00119366 NCT00119366 The purpose of this study is to determine the safety, side effects (good or bad), and how much radiation can be given using treatment with an experimental drug called Iodine-131-radiolabeled BC8 monoclonal antibody (or I-131-BC8), in patients with acute myelogenous leukemia (AML) or high risk myelodysplastic syndrome (MDS). The treatment with the experimental drug will be followed by a chemotherapy drug called fludarabine, a low dose of total body radiation, and a donor stem cell transplant. Some of the treatment will be given in the outpatient clinic at the Seattle Cancer Care Alliance (SCCA). Treatment with the experimental drug, I-131-BC8, will take place at the University of Washington Medical Center. The participant will receive a test dose of I-131-BC8 using a small amount of radiation, followed by imaging tests that will take place over the next few days. About 10 days later, the participant will receive a treatment dose of I-131-BC8 using a much larger dose of radiation. The participant will stay alone in a radiation isolation room at the hospital for about 5 to 10 days after receiving this dose. After the isolation period, participants will receive fludarabine and low dose radiation followed by a stem cell transplant. Participants will also receive the drugs cyclosporine and mycophenolate mofetil starting before or on the day of the transplant and continue taking these drugs for a few weeks or months after transplant. Participants will be in the study for at least 3 ½ months, but possibly longer. After this treatment period, participants will return to the care of their primary oncologist. In order to look at the long-term effects of the study, participants will be asked to allow Fred Hutchinson Cancer Research Center to continue to get information from the referring physician and send questionnaires about participants’ health after the study. It is strongly recommended that thyroid function tests be performed one or more times a year following treatment on this study. - 1) Diagnosed with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS). - AML patients must have AML that has either: - a) come back after first remission, or - b) did not respond to initial treatment, or - c) evolved from myelodysplastic or myeloproliferative syndrome. - MDS patients must have one of the following: - a) refractory anemia with excess blasts (RAEB), - b) RAEB in transformation (RAEBT), - c) refractory cytopenia with multilineage dysplasia (RCMD), - d) RCMD with ringed sideroblasts (RCMD-RS), or - e) chronic myelomonocytic leukemia (CMML). - 2) Must be between 16 and 50 years of age. - 3) Must have normal liver and kidney function (must undergo a 24-hour urine collection to test kidneys). - 4) Must be physically able to meet study requirements. - 5) Must not have active infection. - 6) Must have a healthy, matched, related or unrelated donor according to study guidelines. Other eligibility criteria may apply. - 1) Already received maximum radiation to any organ. - 2) Severe heart problems requiring medication, or symptoms of coronary artery disease. - 3) HIV positive. - 4) Medical or other condition that may prevent the patient from finishing the study. - 5) Already undergone bone marrow or stem cell transplant. Other exclusion criteria may apply. 725ce58e135045e306a565c4a25f8eba 5866 Fludarabine, Radiation Therapy, and Rituximab in Treating Patients Who Are Undergoing Donor Stem Cell Transplant Followed by Rituximab for High-Risk Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma II Mohamed Sorror, MD, MSc 1840.00 11; 18; 36; 43; 48 Bone Marrow and Hematopoietic Stem Cell Transplant (BMT and HSCT); Chronic Lymphoid Leukemia (CLL); Hematologic Malignancies; Leukemia; Lymphoma Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.5866.html http://www.clinicaltrials.gov/ct/search?term=NCT00104858 NCT00104858 This phase II trial is studying how well giving fludarabine phosphate together with radiation therapy and rituximab followed by donor stem cell infusions work in treating patients with high-risk chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) with low side effects. Nonmyeloablative stem cell transplants use low doses of chemotherapy (fludarabine phosphate) and radiation to suppress the patient's immune system enough to prevent rejection of the donor's stem cells. Following infusion of donor stem cells, a mixture of the patient's and the donor's stem cells will exist and is called "mixed chimerism". Donor cells will attack the patient's leukemia. This is called the "graft-versus-leukemia" effect. Rituximab will be given 3 days before and three times after infusing stem cells to help in controlling CLL early after transplant till the "graft-versus-leukemia" takes control. Further, rituximab could augment the "graft-versus-leukemia" effect by activating donor immune cells and hence improve disease control. Sometimes the transplanted cells from a donor can also attack the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Patients with a diagnosis of CLL (or SLL) or diagnosis of CLL that progresses to prolymphocytic leukemia (PLL) - Patients with B-Cell CLL or PLL who: -- a) Failed to meet National Cancer Institute (NCI) Working Group criteria 2 for complete or partial response after 2 cycles of therapy with regimen containing fludarabine (or another nucleoside analog, e.g. cladribine [2-CDA], pentostatin) or with disease relapse within 12 months after completing therapy with a fludarabine (or another nucleoside analog) containing regimen -- b) Failed FCR or pentostatin/cyclophosphamide/rituximab (PCR) combination chemotherapy at any time point -- c) Patients with novo or acquired "17p deletion" cytogenetic abnormality; patients should have received induction chemotherapy but could be transplanted in 1st CR - Patients who have suitable human leukocyte antigen (HLA)-matched related or unrelated donors willing to receive filgrastim (G-CSF), undergo leukapheresis to collect peripheral blood mononuclear cell (PBMC), and to donate stem cells - RELATED DONORS: When more than one potential donor exists, priority should be given to donors based on HLA identity > cytomegalovirus (CMV) seronegativity > ABO compatibility > sex matching -- a) Donor who is HLA phenotypically or genotypically identical at the allele level at HLA-A, -B, -C, -DRB1, and -DQB1 -- b) Must consent to G-CSF administration and leukapheresis; -- c) Must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral, subclavian); -- d) Only G-CSF mobilized PBMC only will be permitted as a hematopoietic stem cell (HSC) source on this protocol - UNRELATED DONORS: -- Fred Hutchinson Cancer Research Center (FHCRC) matching allowed will be Grades 1.0 to 2.1; Unrelated donors who are prospectively: -- a) Matched for HLA-A, B, C, DRB1 and DQB1 by high resolution typing -- b) Only a single allele disparity will be allowed for HLA-A, B, or C as defined by high resolution typing - ** UNRELATED DONORS: Donors are excluded when preexisting immunoreactivity is identified that would jeopardize donor hematopoietic cell engraftment; this determination is based on the standard practice of the individual institution; recommended procedure for patients with 10 of 10 HLA allele level (phenotypic) match is to obtain a panel reactive antibody screens to class I and II antigens for all patients before HCT; if the PRA shows > 10% activity, then flow cytometric or B and T cell cytotoxic cross matches should be obtained; the donor should be excluded if any of the cytotoxic cross match assays are positive; for those patients with an HLA Class I allele mismatch, flow cytometric or B and T cell cytotoxic cross matches should be obtained regardless of the PRA results; a positive anti-donor cytotoxic crossmatch is an absolute donor exclusion - UNRELATED DONORS: Patient and donor pairs homozygous at a mismatched allele in the graft rejection vector are considered a two-allele mismatch, i.e., the patient is A*0101 and the donor is A*0102, and this type of mismatch is not allowed - UNRELATED DONORS: Only G-CSF mobilized PBMC will be permitted as a HSC source on this protocol Other eligibility criteria may apply. - Infection with human immunodeficiency virus (HIV) - Active diagnosis of central nervous system (CNS) involvement with CLL - Patients unwilling to use contraceptive techniques before and for 12 months after HCT - Pregnant women or females who are breastfeeding - The addition of cytotoxic agents for 'cytoreduction' with the exception of tyrosine kinase inhibitors (such as imatinib mesylate), cytokine therapy, hydroxyurea, low dose cytarabine, chlorambucil, or rituxan will not be allowed within three weeks of the initiation of conditioning - Active bacterial or fungal infections unresponsive to medical therapy - Performance status: Karnofsky score < 60 for adult patients - Cardiac ejection fraction < 40%; ejection fraction is required if age > 50 years or there is a history of prior transplant, anthracycline exposure or history of cardiac disease; and poorly controlled hypertension despite multiple antihypertensives - Diffusing capacity of the lung for carbon monoxide (DLCO) < 40%, total lung capacity (TLC) < 40%, forced expiratory volume in 1 second (FEV1) < 40% and/or requiring continuous supplementary oxygen, or severe deficits in pulmonary function testing as defined by pulmonary consultant service; and the FHCRC principal investigator (PI) of the study must approve of enrollment of all patients with pulmonary nodules - Patients with clinical or laboratory evidence of liver disease would be evaluated for the cause of liver disease, its clinical severity in terms of liver function, and the degree of portal hypertension; patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, hepatic damage with bridging fibrosis, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices or hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dl, or symptomatic biliary disease - Patients with active non-hematologic malignancies (except non-melanoma skin cancers); this exclusion does not apply to patients with non-hematologic malignancies that do not require therapy - Patients with a history of non-hematologic malignancies (except non-melanoma skin cancers) currently in a complete remission, who are less than 5 years from the time of complete remission, and have a > 20% risk of disease recurrence; this exclusion does not apply to patients with non-hematologic malignancies that do not require therapy - DONOR: Age < 12 years - DONOR: Identical twin - DONOR: Pregnancy - DONOR: Infection with HIV - DONOR: Inability to achieve adequate venous access - DONOR: Known allergy to filgrastim (G-CSF) - DONOR: Current serious systemic illness Other exclusion criteria may apply. 89c7c2cc1975106cc891fdde6fa9c482 6250 Dose-Intensive Chemotherapy in Combination With Chemoprotected Autologous Stem Cells for Patients With Malignant Gliomas I/II Hans-Peter Kiem, MD 2000.00 12; 33; 83 Brain Cancer; Glioma; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.6250.html http://www.clinicaltrials.gov/ct/search?term=NCT00669669 NCT00669669 This phase I/II trial is studying carmustine and temozolomide when given together with radiation therapy, BCNU, O6-benzylguanine, and an autologous stem cell transplant in treating patients with newly diagnosed glioblastoma multiforme or gliosarcoma. Giving chemotherapy, such as temozolomide, carmustine, and O6-benzylguanine, and radiation therapy before a peripheral stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. Giving colony-stimulating factors, such as filgrastim, and certain chemotherapy drugs, helps stem cells move from the bone marrow to the blood so they can be collected and stored. Chemotherapy or radiation therapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy and radiation therapy Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Patients with glioblastoma multiforme or gliosarcoma - The patient or legal guardian must be able to comprehend the informed consent form and sign prior to patient enrollment - Patients must be consented for MGMT promoter methylation analysis of brain tumor tissue within twenty-eight days after surgery - Karnofsky performance status at time of study entry must be >= 70% - Life expectancy of >= 3 months - Patients must agree to undergo repeat clinical neurological examinations and brain magnetic resonance imaging (MRI) with appropriate contrast after every other cycle of chemotherapy - White blood cell (WBC) > 3000/uL - Absolute neutrophil count (ANC) > 1500/uL - Platelets > 100,000/uL - Hemoglobin > 10 gm/100mL - Total and direct bilirubin < 1.5 times upper limit of laboratory normal - Serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvate transaminase (SGPT), and alkaline phosphatase =< 3 times upper limit of laboratory normal - Blood urea nitrogen (BUN) and serum creatinine < 1.5 times upper limit of laboratory normal - Left ventricular ejection fraction (LVEF) >= 40%, however, subjects with an LVEF in the range of 40-49% should have cardiology clearance prior to intervention - MGMT promoter methylation analysis of surgically resected tumor or tumor biopsy must demonstrate an unmethylated or hypomethylated MGMT promoter status Other eligibility criteria may apply. - Patients with cardiac insufficiency and an LVEF of < 40%; history of coronary artery disease or arrhythmia, which has required or requires ongoing treatment - Patients with active pulmonary infection and/or pulse oximetry < 90% and a corrected diffusion capacity of carbon monoxide (DLCO) < 70% of predicted - Active systemic infection - Patients who are human immunodeficiency virus (HIV) positive - Pregnant or lactating women; a beta-human chorionic gonadotropin (HCG) level will be obtained from women of childbearing potential; fertile men and women should use effective contraception - Previous chemotherapy for any malignancy including temozolomide, dacarbazine (DTIC) or prior nitrosourea - Diabetes mellitus - Bleeding disorder - Methylated or hypermethylated MGMT promoter status within tumor tissue - Medical or psychiatric condition which in the opinion of the protocol chairman would compromise the patient's ability to tolerate this protocol - Prior interstitial radiotherapy, stereotactic or gamma knife surgery or implanted BCNU-wafers Other exclusion criteria may apply. 21adad65edaf8e5a0afd757184405833 6586 Alemtuzumab, Fludarabine Phosphate, and Total-Body Irradiation Followed By a Donor Stem Cell Transplant in Treating Patients With Immunodeficiency or Other Nonmalignant Inherited Disorders II Lauri Burroughs, MD 2007.00 11; 39; 79; 127 Bone Marrow and Hematopoietic Stem Cell Transplant (BMT and HSCT); Immunodeficiency Syndromes; Severe Combined Immunodeficiency Syndrome (SCID); Non-malignant Condition Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.6586.html http://www.clinicaltrials.gov/ct/search?term=NCT00553098 NCT00553098 The purpose of this study is to determine whether or not a non-myeloablative conditioning regimen followed by stem cell transplantation is safe and effective as treatment of non-malignant diseases of the blood and immune system. The chemotherapy and irradiation given just before a transplant is called the conditioning regimen. A non-myeloablative conditioning regimen uses lower doses of chemotherapy and radiation than a conventional conditioning regimen. Most of the treatment will be given at the Seattle Cancer Care Alliance (SCCA) outpatient clinic. Initial in-hospital treatment will be given at the University of Washington Medical Center or Children’s Hospital and Regional Medical Center. Treatment on the study will last about four months (about one month before the transplant and three months after the transplant), but could be longer. Participants may be asked to return for follow-up visits 6 months, and then every year, after the transplantation. Additional bone marrow or blood samples may be drawn at various time points for up to five years after the transplant. • Age 54 years or younger. • Diagnosed with an immunodeficiency or other non-malignant disease that is treatable by allogeneic stem cell transplantation. • Patients with pre-existing medical conditions or other factors that rule out treatment with conventional myeloablative stem cell transplantation. Other eligibility criteria may apply. • Patients with Aplastic anemia and Fanconi anemia • 55 years or older • Patient has HIV • Patient is a female who is pregnant or breast-feeding Other exclusion criteria may apply. ca58917148b9f671ff3b369012b72a47 6587 Fludarabine Phosphate, Cyclophosphamide, and Total-Body Irradiation Followed By Donor Bone Marrow Transplant, Cyclophosphamide, Mycophenolate Mofetil, and Tacrolimus in Treating Patients With Immunodeficiency or Noncancerous Inherited Disorders II Lauri Burroughs, MD 2032.00 11; 39; 79; 127 Bone Marrow and Hematopoietic Stem Cell Transplant (BMT and HSCT); Immunodeficiency Syndromes; Severe Combined Immunodeficiency Syndrome (SCID); Non-malignant Condition Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.6587.html http://www.clinicaltrials.gov/ct/search?term=NCT00358657 NCT00358657 The purpose of this study is to determine the safety of non-myeloablative conditioning and stem cell transplantation for patients with non-malignant inherited disorders who do not have a genetically matched donor. Participants in this study will receive bone marrow donated by a family member whose tissue type is genetically only a partial match. Non-myeloablative conditioning (the chemotherapy and radiation given just before a transplant) uses lower doses of chemotherapy and radiation than conventional conditioning. Most of the treatment will be given at the Seattle Cancer Care Alliance (SCCA) outpatient clinic. Initial in-hospital treatment will be given at the University of Washington Medical Center or Children’s Hospital and Regional Medical Center. Participants will be in the study for at least one year, and will come to the SCCA clinic for treatment for about four months (about one month before the transplant and three months after the transplant). Additional bone marrow or blood samples may be drawn at various time points for up to five years after the transplant. • Age 54 years or younger. • Non-malignant disease treatable by allogeneic stem cell transplantation. • Patient is at high risk of having toxic side effects, or is ineligible for a conventional myeloablative stem cell transplantation, • Patient does not have a genetically matched (HLA-matched, related or unrelated) donor. Other eligibility criteria may apply. • Patients with aplastic anemia, Fanconi anemia • Patients with HLA-matched (genetically matched) related or unrelated donors • Patients with HIV • Patients who are female and are pregnant or breastfeeding Other exclusion criteria may apply. 7b77868da863d52ac21dc340f21e7bb4 6327 Fludarabine-based Conditioning for Severe Aplastic Anemia (BMT CTN 0301) I/II Joachim Deeg, MD 2051.00 5; 11; 127 Aplastic Anemia; Bone Marrow and Hematopoietic Stem Cell Transplant (BMT and HSCT); Non-malignant Condition Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.6327.html http://www.clinicaltrials.gov/ct/search?term=NCT00326417 NCT00326417 This is an unrelated donor transplantation study for patients up to age 65 with severe aplastic anemia.The purpose of this study is to determine what dose of cyclophosphamide should be used, along with other medications before transplantation, to improve the safety and effectiveness of transplantation. The chemotherapy and irradiation given just before a transplant is called the conditioning regimen. Participants in this study will receive a conditioning regimen consisting of fludarabine, cyclophosphamide, and antithymocyte globulin (ATG), as well as low-dose total body irradiation. Different groups of participants will receive different amounts of cyclophosphamide, of which they will be informed. Study participants will then receive a bone marrow transplant using cells from an unrelated donor. Most of the care will be given at the Seattle Cancer Care Alliance (SCCA) outpatient clinic. During the transplant and the initial recovery period, and if needed at different time points after the transplant, participants will be admitted to the UW Medical Center hospital. Participants will be asked to come to the SCCA clinic on a regular basis for exams and blood tests for about 3 months after the transplant. Participants will be followed by their personal physicians for up to 2 years. 1. Patient is 65 years of age or younger. 2. Patient has a diagnosis of Severe Aplastic Anemia. 3. Patient has a suitable, unrelated donor. (The donor cannot be a family member.) 4. Patient may be either female or male. Other eligibility criteria may apply. 1. Clonal cytogenetic abnormalities associated with MDS or AML on marrow examination. 2. Diagnosis of Fanconi anemia. 3. Diagnosis of other “congenital” marrow failure states (such as Diamond-Blackfan, Shwachmann-Diamond, congenital amegakaryocytosis). 4. Symptomatic or uncontrolled heart failure or coronary artery disease. 5. Uncontrolled infection. 6. Blood test results show presence of HIV infection. 7. Pregnancy or breastfeeding. 8. Known allergy to ATG, cyclosporine or tacrolimus. 9. Patient is also enrolled in another phase I study. 10. Patient has had a prior allogeneic marrow or stem cell transplant. 11. Patient has had a prior malignancy, except resected basal cell carcinoma or treated carcinoma in-situ. Other exclusion criteria may apply. e8b02283478d1086e32c3c99c60aeae6 6381 Fludarabine Phosphate and Total Body Irradiation Followed by a Donor Peripheral Stem Cell Transplant in Treating Patients With Myelodysplastic Syndromes or Myeloproliferative Disorders II Brenda Sandmaier, MD 2056.00 2; 11; 36; 43; 61 Acute Myeloid Leukemia (AML); Bone Marrow and Hematopoietic Stem Cell Transplant (BMT and HSCT); Hematologic Malignancies; Leukemia; Myelodysplastic and Myeloproliferative Syndromes (MDS and MPD) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.6381.html http://www.clinicaltrials.gov/ct/search?term=NCT00397813 NCT00397813 This phase II trial studies the side effects and best dose of total-body irradiation when given together with fludarabine phosphate followed by a donor peripheral stem cell transplant in treating patients with myelodysplastic syndromes (MDS) or myeloproliferative disorders (MPD). Giving low doses of chemotherapy, such as fludarabine phosphate, and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. Giving chemotherapy or radiation therapy before or after transplant also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help./,mnjlkj destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening. Genders Eligible for Study: Both - Patients aged >= 50 and < 75 years (yrs) with CMML, or previously untreated MDS or MPD - Patients aged < 50 yrs at high risk for regimen related toxicity using standard high dose regimens; factors considered high risk include pre-existing conditions such as a chronic disease affecting kidneys, liver, lungs, or heart or previous failed HCT - An human leukocyte antigen (HLA)-identical related or an HLA-matched unrelated donor (Fred Hutchinson Cancer Research Center [FHCRC] matching allowed will be Grade 1.0 to 2.1) is available. - Recovery from the effects of previous chemotherapy, with a minimum of 21 days from initiation of last therapy; hydroxyurea or anagrelide may be used to manage elevated cell counts in patients up to the time they begin therapy under this protocol - Patients < 12 yrs of age must be discussed on a case by case basis with the primary investigator (PI) of the protocol prior to registration - A signed informed consent form or minor assent form - MDS: MDS classifiable by the World Health Organization (WHO) system as RA, RARS, refractory cytopenia with multilineage dysplasia (RCMD), RCMD and ringed sideroblasts (RCMD-RS) or RAEB - MDS: No previous myelosuppressive therapy; for the purpose of this protocol myelosuppressive chemotherapy will be defined as chemotherapy given with the intent of inducing a complete remission (e.g., standard 7+3, high dose intermittent ARA-C [HIDAC], or Mylotarg) - MDS: Patients must have < 10% marrow blasts; fewer than 10% marrow blasts must be documented by marrow examination within 3 weeks of initiation of conditioning - CMML: Patients with CMML1 who have not received myelosuppressive therapy must have < 10% marrow blasts; fewer than 10% marrow blasts must be documented by marrow examination within 3 weeks of initiation of conditioning; OR patients with CMML who have progressed beyond CMML1 and have received myelosuppressive chemotherapy must have < 5% marrow blasts; fewer than 5% marrow blasts must be documented by marrow examination within 3 weeks of initiation of conditioning - MPD: Patients with polycythemia vera with persistent thrombotic or hemorrhagic complications despite conventional therapy, or who have progressed to postpolycythemic marrow fibrosis - MPD: Patients with essential thrombocythemia with persistent thrombotic or hemorrhagic complications despite conventional therapy, or who have progressed to myelofibrosis - MPD: Chronic idiopathic myelofibrosis with peripheral blood cytopenias - MPD: Patients must have < 10% marrow blasts; fewer than 10% marrow blasts must be documented by marrow examination within 3 weeks of initiation of conditioning - MPD: No previous myelosuppressive therapy; for the purpose of this protocol myelosuppressive chemotherapy will be defined as chemotherapy given with the intent of inducing a complete remission (e.g., standard 7+3, HIDAC, or Mylotarg) - Atypical CML: Philadelphia chromosome-negative patients with a diagnosis of atypical CML - Atypical CML: Patients must have < 10% marrow blasts; fewer than 10% marrow blasts must be documented by marrow examination within 3 weeks of initiation of conditioning - Atypical CML: No previous myelosuppressive therapy; for the purpose of this protocol myelosuppressive chemotherapy will be defined as chemotherapy given with the intent of inducing a complete remission (e.g., standard 7+3, HIDAC, or Mylotarg) - Paroxysmal nocturnal hemoglobinuria (PNH): Patients with the non-aplastic form of PNH (cellular bone marrow) who have had a history of life-threatening complications of their disease including thrombotic events, severe hemolysis or Budd Chiari syndrome are eligible; other patients may be considered following approval at PCC and approval by the Principal investigator - Matched Related Donor: Related to the patient and is genotypically or phenotypically HLA-identical - Matched Related Donor: Donor age < 75 yrs unless cleared by institutional PI - Matched Related Donor: Capable of giving written, informed consent - Matched Related Donor: Donor must consent to PBSC mobilization with G-CSF and apheresis - Unrelated Donor: FHCRC matching allowed will be Grades 1.0 to 2.1: Unrelated donors who are prospectively: - 1) Matched for HLA-A, B, C, DRB1 and DQB1 by high resolution typing; - 2) Only a single allele disparity will be allowed for HLA-A, B, or C as defined by high resolution typing - Unrelated Donor: Patient and donor pairs homozygous at a mismatched allele in the graft rejection vector are considered a two-allele mismatch, i.e., the patient is A*0101 and the donor is A*0102, and this type of mismatch is not allowed - HLA Matched Related Donor: G-CSF mobilized peripheral blood mononuclear cell (PBMC) only will be permitted as a hematopoietic stem cell (HSC) source on this protocol - HLA Matched Unrelated Donor: Donor must consent to PBSC mobilization with G-CSF and apheresis; bone marrow unrelated donors are not eligible for this protocol Other eligibility criteria may apply. - Organ dysfunction as defined by the following: - 1) Symptomatic coronary artery disease or cardiac ejection fraction < 35% (or, if unable to obtain ejection fraction, shortening fraction of <26%); if shortening fraction is <26% a cardiology consult is required with the PI having final approval of eligibility; ejection fraction is required if age > 50 years or there is a history of anthracycline exposure or history of cardiac disease - 2) Diffusing capacity of the lung for carbon monoxide (DLCO) < 35%, TLC < 35%, forced expiratory volume (FEV)1 < 35% and/or receiving supplementary continuous oxygen; the FHCRC PI of the study must approve of enrollment of all patients with pulmonary nodules - 3) Liver function abnormalities: Patient with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, bridging fibrosis, and the degree of portal hypertension; the patient will be excluded if he/she is found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3mg/dL, or symptomatic biliary disease - Bone marrow documenting blast count >= 10% or >= 5% in CMML patients who have progressed beyond CMML1 and received myelosuppressive chemotherapy - Patients with active non-hematologic malignancies (except non-melanoma skin cancers); this exclusion does not apply to patients with non-hematologic malignancies that do not require therapy - Patients with a history of non-hematologic malignancies (except non-melanoma skin cancers) currently in a complete remission, who are less than 5 years from the time of complete remission, and have a > 20% risk of disease recurrence - Presence of >= 5% circulating leukemic blasts (in the peripheral blood) detected by standard pathology - Active central nervous system (CNS) involvement of disease - Karnofsky performance score < 70% or Lansky-Play Performance score < 70 for pediatric patients - Life expectancy severely limited by diseases other than malignancy - Fungal infections with radiological progression after receipt of amphotericin product or active triazole for > 1 month - Active bacterial infection - Patients of fertile age who refuse contraception for a twelve month period post-transplant - Females who are pregnant or breastfeeding - Human immunodeficiency virus (HIV) seropositivity - Severe psychological illness such as major psychosis (e.g. schizophrenia), major bipolar depression, or suicidal situational depression - Matched Related Donor: Identical twin - Matched Related Donor: Any contra-indication to the administration of subcutaneous G-CSF at a dose of 16mg/kg/d for five consecutive days - Matched Related Donor: Serious medical or psychological illness - Matched Related Donor: Pregnant or lactating females - Matched Related Donor: Prior malignancy within the preceding five yrs, with the exception of non-melanoma skin cancers - Matched Related Donor: HIV seropositivity - Unrelated Donor: A positive anti-donor cytotoxic crossmatch is an absolute donor exclusion; donors are excluded when preexisting immunoreactivity is identified that would jeopardize donor hematopoietic cell engraftment; this determination is based on the standard practice of the individual institution; the recommended procedure for patients with 10 of 10 HLA allele level (phenotypic) match is to obtain a panel reactive antibody (PRA) screens to class I and class II antigens for all patients before HCT; if the PRA shows > 10% activity, then flow cytometric or B and T cell cytotoxic cross matches should be obtained; the donor should be excluded if any of the cytotoxic cross match assays are positive; for those patients with an HLA Class I allele mismatch, flow cytometric or B and T cell cytotoxic cross matches should be obtained regardless of the PRA results - Unrelated Donor: Marrow donors - Unrelated Donor: Donors who are HIV-positive and/or medical conditions that would result in increased risk to the donor G-CSF mobilization and G-PBMC collections - Unrelated Donor: Serious medical or psychological illness - Unrelated Donor: Pregnant or lactating females - Unrelated Donor: Prior malignancy within the preceding five yrs, with the exception of non-melanoma skin cancers - Unrelated Donor: HIV seropositivity Other exclusion criteria may apply. 9a40e26051af0654f3ff376273cc4b79 6788 Fludarabine Phosphate, Cyclophosphamide, and Total-Body Irradiation Followed by Donor Bone Marrow Transplant, Mycophenolate Mofetil, and Cyclosporine in Treating Patients With Fanconi Anemia II Hans-Peter Kiem, MD 2064.00 1; 2; 5; 11; 15; 26; 36; 48; 55; 61 Acute Lymphoid Leukemia (ALL); Acute Myeloid Leukemia (AML); Aplastic Anemia; Bone Marrow and Hematopoietic Stem Cell Transplant (BMT and HSCT); Burkitt's Lymphoma; Fanconi Anemia; Hematologic Malignancies; Lymphoma; Childhood Cancers, Miscellaneous; Myelodysplastic and Myeloproliferative Syndromes (MDS and MPD) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.6788.html http://www.clinicaltrials.gov/ct/search?term=NCT00453388 NCT00453388 This phase II trial is studying how well total-body irradiation (TBI) works when given together with fludarabine phosphate and cyclophosphamide followed by donor bone marrow transplant, mycophenolate mofetil, and cyclosporine in treating patients with Fanconi anemia (FA). Giving low doses of chemotherapy, such as fludarabine phosphate and cyclophosphamide, and TBI before or after a donor bone marrow transplant helps stop the growth of abnormal cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving mycophenolate mofetil and cyclosporine after the transplant may stop this from happening - Genders Eligible for Study: Both - Any patient with FA and bone marrow (BM) failure involving 2 of the following 3 lineages: granulocyte count < 0.5 x 10^9/L, platelet count < 20 x 10^9/L, or hemoglobin < 8 g/dL - Any patient with FA who requires red blood cell or platelet transfusions because of marrow failure - Any patient with FA who has a life-threatening BM failure involving a single hematopoietic lineage - Any patient with FA and pre-existing cytogenetic abnormality including hematopoietic malignancy (acute myeloid leukemia [AML] or myelodysplastic syndrome [MDS]) in morphological remission (defined as absence of circulating blasts and bone marrow blasts < 5% as assessed by morphology); Note that hematopoietic recovery is not required for remission status - Patients must have a negative cytotoxic cross match with donor - DONOR: Related, human leukocyte antigen (HLA)-haploidentical donors must be identical for one HLA haplotype and mismatched for any number of HLA-A, -B, -C, DRB1 or DQB1 loci of the unshared haplotype - DONOR: Unrelated, HLA-matched donors must be matched at HLA-A, B, C, DRB1 and DQB1 by Deoxyribonucleic acid (DNA) typing at the highest resolution routinely available at the time of donor selection; a single allele mismatch at HLA-A, B, or C is allowed OR a single DQB1 mismatch is allowed - DONOR: Bone marrow will be the only allowed hematopoietic stem cell source - DONOR: Haploidentical donor selection will be based on standard institutional criteria, otherwise no specific prioritization will be made amongst the suitable available donors Other eligibility criteria may apply. - Patients having available HLA-matched related donors - Significant organ dysfunction that would prevent compliance with conditioning, GVHD prophylaxis, or would severely limit the probability of survival, such as liver disease/failure (active hepatitis, moderate to severe portal fibrosis/cirrhosis confirmed by biopsy or uncorrectable hepatic synthetic dysfunction), lung disease, or cardiac disease (ejection fraction < 35%, or if unable to obtain ejection fraction, shortening fraction of < 26%; if shortening is < 26% a cardiology consult is required with principal investigator [PI] having final approval of eligibility) - Human immunodeficiency virus (HIV) seropositive patients - Fertile females who are unwilling to use contraceptive techniques during and for the twelve months following treatment, as well as females who are pregnant or actively breast feeding - Fertile males who are unwilling to use contraceptive techniques during and for the twelve months following treatment - AML/MDS in morphological relapse, defined as having circulating blasts or bone marrow blasts >= 5% as assessed by morphology - Active infectious disease concerns - Karnofsky performance score < 50 or Lansky performance score < 40 - DONOR: Donors found to have Fanconi Anemia based on chromosomal breakage analysis - DONOR: Donors who are not expected to meet the minimum target dose of marrow cells (1 x 10^8 nucleated cells/kg recipient ideal body weight [IBW]) or who are unwilling to be bone marrow donors - DONOR: HIV-positive donors - DONOR: Donors who are cross-match positive with recipient - DONOR: Recipient homozygous at mismatched locus; if the recipient is homozygous at HLA-A, B, or C and the donor is mismatched at that locus, the donor should be avoided; exceptions must be discussed with the primary investigator (PI) Other exclusion criteria may apply. 47be72e91122587ff35ce0bd7ba87d11 6554 Nonmyeloablative transplant for severe systemic sclerosis I/II George Georges, MD 2067.00 7; 78; 85; 127 Autoimmune Diseases; Scleroderma; Systemic Sclerosis; Non-malignant Condition Bernadette McLaughlin bmclaugh@fhcrc.org 206/667-4916 http://www.fhcrc.org/en/treatment/clinical-trials/detail.6554.html http://www.clinicaltrials.gov/ct/search?term=NCT00622895 NCT00622895 Study Purpose: The major goal of this project is to determine if non-myeloablative stem cell transplantation is an effective treatment for severe systemic sclerosis (SSc). SSc is an autoimmune disease in which a person’s immune system attacks skin and internal organs that leads to scarring and dysfunction. For persons with severe SSc, there exists no effective therapy to halt disease progression, and conventional transplantation is not well tolerated by all SSc patients. Non-myeloablative transplant treatments use lower doses of chemotherapy and radiation than conventional transplant treatments. Study Sites: Participants will receive treatment at the Seattle Cancer Care Alliance (SCCA) and the University of Washington. Study Duration and Follow-up: Participation in the active treatment phase of the study (the transplantation) will last approximately 3 months. Following the transplantation, participants will receive regularly scheduled medical evaluations the first year. Thereafter, participants will have follow-up testing once a year through five years. • Males or females • Ages up to 70 • Severe Systemic Sclerosis with evidence of moderate to severe skin involvement, lung involvement, history of kidney disease and failure of treatment with cyclophosphamide. • Availability of a matched sibling or unrelated stem cell donor Other eligibility criteria may apply. • Age over 70 • Lack of suitable donor • Eligible for autologous transplant study (SCOT trial) • Severe organ dysfunction (such as heart, lung, liver, etc.) • Untreated psychiatric conditions • Other cancers • HIV positivity • Severe infections • Pregnancy • Lack of willingness to use contraceptive techniques Other exclusion criteria may apply. b1b5dc0a4b785fb90cb07d279da21b55 7332 Autologous or Syngeneic Stem Cell Transplant Followed by Donor Stem Cell Transplant and Bortezomib in Treating Patients With Newly Diagnosed High-Risk, Relapsed, or Refractory Multiple Myeloma II Marco Mielcarek, MD 2070.00 36; 57 Hematologic Malignancies; Multiple Myeloma (MM) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.7332.html http://www.clinicaltrials.gov/ct/search?term=NCT00793572 NCT00793572 This phase II trial is studying the side-effects and anti-cancer effects of giving an autologous or syngeneic stem cell transplant followed by an allogeneic donor stem cell transplant and bortezomib. Patients treated on this trial have newly diagnosed high-risk, relapsed, or refractory multiple myeloma (MM). Giving chemotherapy before an autologous stem cell transplant slows or stops the growth of cancer cells by preventing them from dividing or killing them. Stem cells that were harvested earlier from the patient's blood and frozen are then returned to the patient to replace the blood-forming cells that were destroyed by chemotherapy. Giving chemotherapy and total-body irradiation before an allogeneic donor stem cell transplant also prevents the patient's immune system from rejecting the donor's stem cells. Undergoing an autologous or syngeneic stem cell transplantation followed by an allogeneic donor stem cell transplant and bortezomib may be overall more effective in killing cancer cells Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Newly diagnosed patients must have received induction therapy (e.g., vincristine, doxorubicin, dexamethasone [VAD], thalidomide/dexamethasone) for a minimum of 4 cycles - Must have the capacity to give informed consent - Must have an human leukocyte antigen (HLA) genotypically identical sibling or a phenotypically matched relative or, at a minimum, a high likelihood of identifying an HLA-matched unrelated donor; the determination of availability of a suitable unrelated donor may be based on a World-Book search - In addition, patients must meet at least one of the criteria A-I (A-G at time of diagnosis or pre-autograft): - A) Any abnormal karyotype by metaphase analysis except for isolated t(11,14) and constitutional cytogenetic abnormality - B) Fluorescence in situ hybridization (FISH) translocation 4;14 - C) FISH translocation 14;16 - D) FISH deletion 17p - E) Beta2-microglobulin > 5.5 mg/mL - F) Cytogenetic hypodiploidy - G) Plasmablastic morphology (>= 2%) - H) Recurrent or non-responsive (less than partial response [PR]) MM after at least two different lines of conventional chemotherapy - I) Progressive MM after a previous autograft (provided stored autologousCD34 cells are available) - DONOR: HLA genotypically identical sibling or phenotypically matched relative OR - DONOR: HLA phenotypically matched unrelated donor (according to Standard Practice HLA matching criteria, Grade #2.1) --- Matched HLA-A, B, C, DRB1, and DQB1 alleles by high resolution typing. --- Only a single allele disparity will be allowed for HLA-A, B, or C as defined by high resolution typing Other eligibility criteria may apply. - Life expectancy severely limited by disease other than malignancy - Seropositive for the human immunodeficiency virus (HIV) - Females who are pregnant or breastfeeding - Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment - Patients with active non-hematological malignancies (except non-melanoma skin cancers) or those with non-hematological malignancies (except non-melanoma skin cancers) who have been rendered with no evidence of disease, but have a greater than 20% chance of having disease recurrence within 5 years; this exclusion does not apply to patients with non-hematologic malignancies that do not require therapy - Patients with fungal infection and radiological progression after receipt of amphotericin B or active triazole for greater than 1 month - Patients with the following organ dysfunction: - a) Symptomatic coronary artery disease or ejection fraction < 40% or other cardiac failure requiring therapy; myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities - b) Ejection fraction is required if the patient has a history of anthracyclines or history of cardiac disease; - c) Diffusing lung capacity for carbon monoxide (DLCO) < 50%, forced expiratory volume in 1 second (FEV) < 50% and/or receiving supplementary continuous oxygen; the Fred Hutchinson Cancer Research Center (FHCRC) principle investigator (PI) of the study must approve of enrollment of all patients with pulmonary nodules - d) Liver function abnormalities: Patient with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, bridging fibrosis, and the degree of portal hypertension; the patient will be excluded if he/she is found to have fulminant liver failure; cirrhosis of the liver with evidence of portal hypertension; alcoholic hepatitis; esophageal varices; a history of bleeding esophageal varices; hepatic encephalopathy; uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time OR ascites related to portal hypertension; bacterial or fungal liver abscess; biliary obstruction; chronic viral hepatitis with total serum bilirubin > 3mg/dL; and symptomatic biliary disease; - e) Karnofsky score < 70% for adult patients - Patient with poorly controlled hypertension and on multiple antihypertensives - Patients with >= grade 2 peripheral neuropathy - Patient has an active bacterial or fungal infection unresponsive to medical therapy - DONOR: Identical twin - DONOR: Donors unwilling to donate PBSC - DONOR: Pregnancy - DONOR: Infection with HIV - DONOR: Inability to achieve adequate venous access - DONOR: Known allergy to G-CSF - DONOR: Current serious systemic illness - DONOR: Failure to meet FHCRC criteria for stem cell donation - DONOR: Age < 12 years - DONOR: A positive anti-donor cytotoxic crossmatch - DONOR: Patient and donor pairs must not be homozygous at mismatched allele Other exclusion criteria may apply. 0af7145514b00f97d180fe2ddd5e1e91 7241 Gene Therapy for Fanconi Anemia I Pamela Becker, MD, PhD 2097.00 21; 26; 127 Diamond Blackfan Anemia; Fanconi Anemia; Non-malignant Condition Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.7241.html http://www.clinicaltrials.gov/ct/search?term=NCT01331018 NCT01331018 This pilot trial will assess the toxicity and efficacy of infusion of gene modified cells, as well as the feasibility of mobilization of peripheral blood stem cells with filgrastim and plerixafor for patients with Fanconi anemia (FA). Infusion of autologous patient blood stem cells that have been corrected in the laboratory by introduction of the normal gene may improve blood counts in patients with FA - FA demonstrated by a positive test for increased sensitivity to chromosomal breakage with mitomycin C or diepoxybutane performed by a Clinical Laboratory Improvement Amendments (CLIA) or College of American Pathologists (CAP) approved laboratory - FA complementation group A as determined by somatic cell hybrids, molecular characterization, Western blot analysis, or acquisition of mitomycin C resistance after in vitro lentiviral transduction with a vector bearing the cDNA for Fanconi complementation group A - Bone marrow analysis demonstrating normal cytogenetics, and no more than 5% of cells with a single clonal abnormality by fluorescence in situ hybridization (FISH) for myelodysplastic syndrome (MDS) panel within 3 months of stem cell collection - Signed informed consent by the patient or legally authorized representative - Absolute neutrophil count >= 0.7 X 10^9/L - Hemoglobin >= 8 g/dl - Platelet count >= 20 X 10^9/L and able to achieve a platelet count of >= 50 X 10^9/L with transfusion support - Adequate hepatic function with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 5 X upper limit normal (UPN) - Adequate renal function with Creatinine =< 1.5; if greater, then glomerular filtration rate (GFR) > 60 ml/min/ 1.73 m^2 as calculated by the Modification of Diet in Renal Disease equation - Adequate pulmonary function with corrected diffusion capacity of carbon monoxide (DLCO) > 50% - For subjects < 17 years of age, Modified Lansky Play-Performance Score of >= 70%; for subjects 17 and older, Karnofsky score of >= 70% Other eligibility criteria may apply. - Non-hematopoietic malignancy where the expected survival is less than 2 years - Myelodysplastic syndrome as defined by World Health Organization (WHO) criteria - Acute myeloid leukemia as defined by WHO criteria - Pregnancy or lactation; females of childbearing potential and males who are admitted to the study will be advised that the study procedures and study drugs may be teratogenic, and they will be required to take adequate measures to prevent conception for the duration of the study - Concurrent enrollment in any other study using an investigational drug - Physical or emotional status that would prevent informed consent, protocol compliance, or adequate follow-up - Significant associated diseases including documented human immunodeficiency virus (HIV) infection, uncontrolled hypertension (diastolic blood pressures > 95%ile for age), unstable angina, congestive heart failure (> New York Heart Association [NY] II), poorly controlled diabetes (Hgb A1c > 7%), coronary angioplasty within 6 months, myocardial infarction within the last 6 months, or uncontrolled atrial or ventricular cardiac arrhythmia, abnormal coagulation, persistent abnormal urinalysis reflecting intrinsic renal disease - Active ongoing viral, bacterial, or fungal infection Other exclusion criteria may apply. bcc1c50c901ed45f4a29347f2d80a41d 7568 Selective Depletion of CD45RA+T Cells From Allogeneic Peripheral Blood Stem Cell Grafts for the Prevention of GVHD II Marie Bleakley, MD 2222.00 1; 2; 11; 36; 43; 55; 61 Acute Lymphoid Leukemia (ALL); Acute Myeloid Leukemia (AML); Bone Marrow and Hematopoietic Stem Cell Transplant (BMT and HSCT); Hematologic Malignancies; Leukemia; Childhood Cancers, Miscellaneous; Myelodysplastic and Myeloproliferative Syndromes (MDS and MPD) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.7568.html http://www.clinicaltrials.gov/ct/search?term=NCT00914940 NCT00914940 The purpose of this study is to determine the effects, good or bad, of an experimental type of transplant in people with acute leukemia or advanced myelodysplastic syndromes. This study is being done to see whether or not this type of transplant protects study participants against graft-vs-host disease (GVHD). (GVHD is a complication that can happen after a transplant.) The type of transplant used in this study is called a selective T-cell depleted transplant. Certain cells (CD45RA+ naive T-cells) will be removed from the donated stem cells in the laboratory after the cells are collected from the donor but before they are given to the study participant. The naïve T cells are thought to cause GVHD. Participants will receive outpatient treatment at the Seattle Cancer Care Alliance (SCCA) and will be admitted to the University of Washington Medical Center (UWMC) or Seattle Children’s for those parts of their care requiring hospitalization. All study procedures will be completed by about one year after transplant. After that point we will be monitoring study participants as part of the long-term follow-up program for post-transplant complications. • Diagnosed with acute lymphocytic leukemia (ALL) or acute myeloid leukemia (AML) or advanced myleodysplastic syndrome (MDS) • Age 14-55 • Eligible for allogeneic hematopoietic stem cell transplantation (HSCT) • Appropriately matched, sibling donor is available Other eligibility criteria may apply. • Pregnant or breast-feeding • Undergoing second hematopoietic stem cell transplantation (HSCT) • Central nervous system (CNS) involvement that does not respond to intrathecal chemotherapy and/or standard cranial-spinal radiation • HIV+ • Uncontrolled infections • Organ dysfunction • Known hypersensitivity to tacrolimus Other exclusion criteria may apply. fd00c3884c6ae46d1a58870220ead895 7564 Laboratory-Treated T Cells With or Without Ipilimumab in Treating Patients With Metastatic Melanoma I/II Aude Chapuis, MD 2225.00 52; 83 Melanoma; Solid Tumors Rebecca Rodmyre, T-cell Trials Study Line tcelltrials@fhcrc.org 206/667-1539 http://www.fhcrc.org/en/treatment/clinical-trials/detail.7564.html http://www.clinicaltrials.gov/ct/search?term=NCT00871481 NCT00871481 This phase I/II trial is studying the side effects of giving laboratory-treated T cells and ipilimumab together to see how well they work in treating patients with metastatic melanoma. Treating a patient's T cells in the laboratory may help the T cells kill more tumor cells when they are put back in the body. Monoclonal antibodies, such as ipilimumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving laboratory-treated T cells together with ipilimumab may kill more tumor cells - Ages Eligible for Study: 18 Years and older - Genders Eligible for Study: Both - Histopathologic documentation of melanoma concurrent with the diagnosis of metastatic disease - Expression of human leukocyte antigen (HLA)-A2 - Eastern Cooperative Oncology Group (ECOG)/Zubrod performance status of 0-1 - Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study in such a manner that the risk of pregnancy is minimized; suggested precautions should be used to minimize the risk or pregnancy for at least 1 month before start of therapy, and while women are on study for up to 3 months after T cell infusion, and at least 8 weeks after the study drug is stopped; WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal - Men must be willing and able to use an acceptable method of birth control, for at least 3 months after completion of the study, if their sexual partners are WOCBP - Willing and able to give informed consent - Adequate venous access-consider peripherally inserted central catheter (PICC) or central line - Bi-dimensionally measurable disease by palpation on clinical exam, or radiographic imaging (X-ray, computed tomography [CT] scan) - At least 4 weeks must have elapsed since the last chemotherapy, radiotherapy or major surgery; at least 6 weeks for nitrosoureas, mitomycin C and liposomal doxorubicin; if started before T-cell administration, Ipilimumab infusions must be least 21 days apart - Toxicity related to prior therapy must either have returned to =< grade 1, baseline, or been deemed irreversible - Persons of reproductive potential must agree to use and utilize an adequate method of contraception throughout treatment and for at least 8 weeks after study drug is stopped Other eligibility criteria may apply. - Patients with active infections or oral temperature > 38.2 C within 72 hours prior to planned leukapheresis; the procedure may be deferred - Patients with hematocrit (Hct) < 30%, white blood cells (WBC) < 2500/uL and platelets < 50,000 immediately prior to leukapheresis; the procedure may be deferred - Any other malignancy from which the patient has been disease-free for less than 5 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix - White blood cell count (WBC) < 2000/uL - -Hematocrit (Hct) < 24% or hemoglobin (Hb) < 8 g/dL - Absolute neutrophile count (ANC) < 1000 - Platelets < 50,000 - Creatinine > 3.0 x upper limit normal (ULN) - Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 2.5 x ULN - Bilirubin > 3 x ULN - Pregnant women, nursing mothers, men or women of reproductive ability who are unwilling to use effective contraception; women of childbearing potential with a positive pregnancy test within 3 days prior to entry - Clinically significant pulmonary dysfunction, as determined by medical history and physical exam; patients so identified will undergo pulmonary functions testing and those with forced expiratory volume in one second (FEV1) < 2.0 L or diffusion capacity of carbon monoxide (DLco) (corr for Hgb) < 50% will be excluded - Significant cardiovascular abnormalities as defined by any one of the following: - 1) Congestive heart failure - 2) Clinically significant hypotension - 3) Symptoms of coronary artery disease - 4) Presence of cardiac arrhythmias on electrocardiogram (EKG) requiring drug therapy - 5) Ejection fraction < 50 % (echocardiogram or multi gated acquisition [MUGA] scan) - Active and untreated central nervous system (CNS) metastasis (including metastasis identified during screening magnetic resonance imaging [MRI] or contrast CT) - Autoimmune disease: Patients with a history of Inflammatory Bowel Disease are excluded from this study, as are patients with a history of autoimmune disease (e.g. systemic lupus erythematosus, vasculitis, infiltrating lung disease) whose possible progression during treatment would be considered by the Investigator to be unacceptable - Any underlying medical or psychiatric condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events, such as a condition associated with frequent diarrhea - Positive screening tests for human immunodeficiency virus (HIV), hepatitis (Hep) B, and Hep C; if positive results are not indicative of true active or chronic infection, the patient can be treated - Steroids are not permitted 3 days prior to T cell infusion and concurrently during therapy - No prisoners or children will be enrolled on this study - Any non-oncology vaccine therapy used for the prevention of infectious disease within 1 month before or after any ipilimumab dose - Patients may not be on any other treatments for their cancer aside from those included in the protocol; patients may not undergo another form of treatment concurrently with this study Other exclusion criteria may apply. 997f3196d10dee503ddbddbc6aab5616 7570 Rituximab in Treating Patients Undergoing Donor Peripheral Blood Stem Cell Transplant for Relapsed or Refractory B-Cell Lymphoma II Andrew Rezvani, MD 2226.00 15; 36; 38; 48; 49; 64 Burkitt's Lymphoma; Hematologic Malignancies; Hodgkin's Lymphoma; Lymphoma; Lymphoproliferative Disease; Non-Hodgkin's Lymphoma (NHL) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.7570.html http://www.clinicaltrials.gov/ct/search?term=NCT00867529 NCT00867529 This clinical trial studies rituximab in treating patients undergoing donor peripheral blood stem cell transplant for relapsed or refractory B-cell lymphoma. Monoclonal antibodies, such as rituximab, can block cancer cell growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cell-killing substances to them. Giving rituximab before and after donor peripheral blood stem cell transplant may kill more cancer cells and may help the patient's immune system from rejecting the donor's stem cells Genders Eligible for Study: Both Accepts Healthy Volunteers: No - A diagnosis of CD20-expressing B-cell malignancy of any histologic type or grade for whom non-myeloablative allogeneic transplant is considered an appropriate treatment option - Enrolled on a non-myeloablative allogeneic HCT protocol employing total-body irradiation (TBI)-based conditioning of =< 4 Gy, with or without fludarabine; this protocol may be used as an adjunct to the allogeneic arm of a tandem autologous/allogeneic transplant protocol, provided the allogeneic conditioning meets the above criteria - Receiving unmodified peripheral blood mononuclear cell graft products - Patients with an appropriate related or unrelated donor; human leukocyte antigen (HLA)-haploidentical donors are excluded - Able to give informed consent (if >= 18 years of age), or with a legal guardian capable of giving consent (if < 18 years of age) Other eligibility criteria may apply. - Ineligible for non-myeloablative allogeneic HCT - Receiving an HLA-haploidentical allograft - Are fertile but unwilling to use contraception during and for at least 12 months after HCT - Females who are pregnant or breast-feeding Other exclusion criteria may apply. 9e75616cd4e953702e3cafc24654c0f5 8162 Azacitidine and Gemtuzumab Ozogamicin in Treating Patients With Relapsed Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia Who Have Undergone Stem Cell Transplant II Bart Scott, MD 2240.00 2; 36; 43; 61 Acute Myeloid Leukemia (AML); Hematologic Malignancies; Leukemia; Myelodysplastic and Myeloproliferative Syndromes (MDS and MPD) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8162.html http://www.clinicaltrials.gov/ct/search?term=NCT01083706 NCT01083706 Purpose This phase II trial studies how well azacitidine works in treating patients with relapsed myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), or acute myeloid leukemia (AML) who have undergone stem cell transplant. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing Genders Eligible for Study: Both - MDS, CMML or AML patients (as diagnosed by World Health Organization [WHO] criteria) with evidence of relapse or progression at >= day 28 and < day 100 post-transplant - Recurrent or increased cytogenetic abnormalities by standard karyotype or fluorescence in situ hybridization (FISH) (the cytogenetic abnormalities must have been previously documented at some time point between diagnosis and date of stem cell transplant) - Morphologic evidence of recurrence or increased abnormal myeloblasts in peripheral blood or marrow - Flow Cytometric evidence of disease as determined by recurrent or increased abnormal myeloblasts in peripheral blood or marrow - Extramedullary relapse (local radiotherapy will be allowed) - MDS, CMML, or AML patients with persistent stable disease or persistent disease with regression at >= day 28 and < day 100 post-transplant; the inclusion of patients with persistent stable or persistent regressing disease in this protocol is not meant to advocate treatment; however, if the attending physician is inclined to offer treatment then these patients would be eligible for this study - Persistence of cytogenetic abnormalities by standard karyotype or FISH - Persistent morphologic evidence of abnormal myeloblasts (in patients with CMML the monoblastoid population is included) in peripheral blood or marrow - Persistent flow cytometric evidence of abnormal myeloblasts (in patients with CMML the monoblastoid population is included) in peripheral blood or marrow - Extramedullary persistence or regression Other eligibility criteria may apply. - Refractory disease at time of stem cell transplant; patients who received chemotherapy prior to transplant with no evidence of response by International Working Group (IWG) criteria - >= 10% bone marrow myeloblasts as measured by morphology - Evidence of central nervous system (CNS) disease at time of relapse by morphology or flow (a diagnostic lumbar puncture [LP] is not required at time of relapse) - Serum creatinine > 2 x ULN (upper limit of normal) - Aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) > 2x ULN - Performance status > 2 (Eastern Cooperative Oncology Group [ECOG] Scale) - Patients with severe disease other than MDS, CMML or AML which would be expected to prevent compliance with treatment - Patients with severe infections (pneumonia, sepsis, etc) within the 2 weeks prior to the anticipated start of protocol treatment Other exclusion criteria may apply. a22d9094e7a53f5ad4f6a128b08850e3 7645 Treosulfan and Fludarabine Before Donor Stem Cell Transplant in Treating Patients With Nonmalignant Inherited Disorders II Lauri Burroughs, MD 2256.00 21; 80; 121; 127 Diamond Blackfan Anemia; Sickle Cell Anemia; Umbilical Cord Blood Transplant (UCBT); Non-malignant Condition Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.7645.html http://www.clinicaltrials.gov/ct/search?term=NCT00919503 NCT00919503 The purpose of this phase II clinical trial is to see if the combination of two chemotherapy drugs, treosulfan and fludarabine with or without low dose radiation, just prior to stem cell transplantation is safe and effective in patients with nonmalignant (noncancerous) diseases. Hematopoietic cell transplantation has been shown to be curative for many patients with nonmalignant (noncancerous) diseases such as primary immunodeficiency disorders, bone marrow failure syndromes, hemoglobinopathies, and inborn errors of metabolism (metabolic disorders). Powerful chemotherapy drugs and/or radiation are often used to condition the patient before infusion of the new healthy donor cells. The purpose of the conditioning therapy is to destroy the patient's abnormal bone marrow which doesn't work properly in order to make way for the new healthy donor cells which functions normally. Although effective in curing the patient's disease, many hematopoietic cell transplantation regimens use intensive chemotherapy and/or radiation which can be quite toxic, have significant side effects, and can potentially be life-threatening. Investigators at the Fred Hutchinson Cancer Research Center in collaboration with Oregon Health & Sciences University, Vanderbilt University, and Medical College of Wisconsin are investigating whether a new conditioning regimen that uses less intensive drugs (treosulfan and fludarabine) with or without low dose radiation results in engraftment of the new donor cells without increased toxicities in patients with nonmalignant (noncancerous) diseases Ages Eligible for Study: up to 54 Years Genders Eligible for Study: Both - Patients with a nonmalignant disease treatable by allogeneic HCT - Patients with a known nonmalignant disease that is not clearly defined will need to be discussed with the protocol principal investigator (PI) (Dr. Lauri Burroughs) and potentially the nonmalignant board to determine if they are eligible for HCT on this study - DONOR: Human leukocyte antigens (HLA)-identical related donors or unrelated donors matched for HLA-A, B, C, DRB1, and DQB1 or mismatched for a single allele at HLA-A, B, C, DRB1 or a single DQB1 antigen or allele mismatch by high resolution deoxyribonucleic acid (DNA) typing - DONOR: Bone marrow is the preferred cell source; PBSC are allowed if donor refuses or is unable to give marrow - DONOR, Umbilical Cord Blood: Unit selection is based on the cryopreserved total nucleated cell (TNC) dose and matching at HLA-A, B antigen level and DRB1 allele level typing. While HLA-C antigen/allele level typing is not considered in the matching criteria, if available, may be used to optimize unit selection. - DONOR, Umbilical Cord Blood: The patient and the cord blood unit(s) must be matched for at least 4 of 6 loci as defined above. - DONOR, Umbilical Cord Blood: Selection of two UCB units is allowed to provide sufficient cell dose Other eligibility criteria may apply. - Patients with idiopathic aplastic anemia and Fanconi anemia; (patients with aplastic anemia associated with paroxysmal nocturnal hemoglobinuria [PNH] or inherited marrow failure syndromes, except Fanconi anemia, will be allowed) - Patients with impaired cardiac function as evidenced by ejection fraction < 35% (or, if unable to obtain ejection fraction, shortening fraction of < 26%) or cardiac insufficiency requiring treatment or symptomatic coronary artery disease; patients with a shortening fraction < 26% may be enrolled if approved by a cardiologist - Patients with impaired pulmonary function as evidenced by diffusion capacity of the lung for carbon monoxide (DLCO) < 50% of predicted (or, if unable to perform pulmonary function tests, then oxygen [O2] saturation < 92% on room air) - Patients with impaired renal function as evidenced by creatinine-clearance < 50% for age, weight, height or serum creatinine > 2X upper normal limit or dialysis-dependent - Patients with evidence of synthetic dysfunction or severe cirrhosis requiring deferral of conditioning as recommended by a gastroenterology specialist - Patients with an active infectious disease requiring deferral of conditioning; as recommended by an infectious disease specialist - Patients who are seropositive for human immunodeficiency virus (HIV) - Females who are pregnant or breast-feeding - Patients with a known hypersensitivity to treosulfan and/or fludarabine - Receiving another experimental drug within 4 weeks of initiation of conditioning (day -6) - DONOR: Deemed unable to undergo marrow harvesting or PBSC mobilization and leukapheresis - DONOR: HIV-positive - DONOR: With active infectious hepatitis - DONOR: Females with a positive pregnancy test Other exclusion criteria may apply. 3ee00326b9ea05b519bdede952321e4e 7857 Bortezomib and Vorinostat as Maintenance Therapy After Autologous Stem Cell Transplant for Non-Hodgkin Lymphoma II Leona Holmberg, MD, PhD 2292.00 11; 36; 48; 64 Bone Marrow and Hematopoietic Stem Cell Transplant (BMT and HSCT); Hematologic Malignancies; Lymphoma; Non-Hodgkin's Lymphoma (NHL) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.7857.html http://www.clinicaltrials.gov/ct/search?term=NCT00992446 NCT00992446 This phase II trial is studying the side effects and how well bortezomib and vorinostat work in treating patients with non-Hodgkin lymphoma (NHL) after an autologous stem cell transplant (ASCT). Bortezomib and vorinostat in the laboratory may stop the growth of lymphoma cells and make them more likely to die. Giving bortezomib together with vorinostat after an ASCT may thus kill any lymphoma cells that remain after transplant. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both Inclusion Criteria for Autologous Transplant: - Diagnosis of NHL, transformed B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, diffuse large B-cell or T-cell lymphoma, and deemed a candidate for autologous transplant - American Heart Association Class I: patients with cardiac disease but without resulting limitation of physical activity; ordinary physical activity does not cause undue fatigue, palpitation, dyspnea, or anginal pain; additionally, patients > 60 years of age must have a left ventricular ejection fraction of at least >= 40% demonstrated by multi gated acquisition scan (MUGA) or echocardiogram (ECG) - Total bilirubin (TB) =< 1.5 mg/dL - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3x the upper limit of normal (ULN) - Creatinine clearance (CrCL) (calculated creatinine clearance is permitted) > 40 mL/min - Diffusing capacity of carbon monoxide (DLCO), forced expiratory volume in one second (FEV1), and forced vital capacity (FVC) >= 50% of predicted (corrected for hemoglobin) - Autologous graft with a minimum of >= 3.0 x 10^6 CD34+ cells/kg; not CD34 selected - Signed informed consent - Female patients of childbearing potential has a negative serum pregnancy test beta-human chorionic gonadotropin (hCG) - Female patient is either post menopausal, free from menses for >= 2 years, surgically sterilized, or willing to use 2 adequate barrier methods of contraception to prevent pregnancy or agrees to abstain from heterosexual activity throughout the study - Male patient agrees to use an adequate method of contraception for the duration of the study - Inclusion Criteria for Maintenance Therapy: - 30-120 days post ASCT for NHL - CrCL >= 40 ml/min - Platelets (PLT) >= 75,000 cells/mm^3 for 5 days after recovery from ASCT nadir - Absolute neutrophil count (ANC) >= 1,500 cells/mm^3 for 5 days after recovery from ASCT nadir - TB =< 1.5 x ULN - AST/ALT =< 2.5 x ULN Other eligibility criteria may apply. Exclusion Criteria for Transplant: - Karnofsky performance score < 70% - Uncontrolled bacterial, viral, or fungal infection (currently taking medication and with progression or no clinical improvement) - Pregnant or breastfeeding - Fertile men and women unwilling to use contraceptive techniques from the time of transplant until one month post maintenance therapy - Prior autologous or allogeneic hematopoietic stem cell transplantation (HSCT) - Patients with evidence of myelodysplastic syndromes (MDS)/acute myeloid leukemia (AML) or abnormal cytogenetics analysis indicative of MDS on the pre-transplant bone marrow examination - Prolonged QTC on electrocardiogram (EKG) - Poorly-controlled diabetes mellitus (DM) - >= grade 2 peripheral neuropathy - Prior history of human immunodeficiency virus (HIV) positivity or known history of hepatitis B or C - Previous history of hypersensitivity to Bortezomib, boron, or mannitol; known hypersensitivity to the components of study drug or its analogs - Require therapeutic anticoagulation treatment, especially with coumadin - Patient who has had chemotherapy, radiotherapy, or biological therapy, within 30 days (42 days for nitrosoureas or mitomycin C) or who has not recovered from adverse events due to agents administered more than 30 days earlier - Patient is currently participating or has participated in a study with an investigational compound or devise within 30 days of initial dosing with study drug(s) - Patient had prior treatment with an histone deacetylase (HDAC) inhibitor (e.g., romidepsin [Depsipeptide], NSC-630176, MS 275, LAQ-824, belinostat [PXD-101], LBH589, MGCD0103, CRA024781, etc); patients who have received compounds with HDAC inhibitor-like activity, such as valproic acid, as anti-tumor therapy should not enroll in this study; patients who have received such compounds for other indications, e.g. valproic acid for epilepsy, may enroll after a 30-day washout period - History of central nervous system (CNS) disease - Symptomatic ascites or pleural effusions - Patient has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial - Patient is, at the time of signing informed consent, a regular user (including "recreational use") of any illicit drugs, substance abuse or had a recent history (within the last year) of drug or alcohol abuse - Patient with a history of a prior malignancy with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma or an in situ malignancy; adequately treated localized prostate carcinoma with prostate-specific antigen (PSA) < 1.0; or who has undergone potentially curative therapy with no evidence of disease for five years, and/or who is deemed at low risk for recurrence by his/her treating physician - Patient has a history or current evidence of any condition, therapy, or lab abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study or is not in the best interest of the patient to participate - Patient has a history of a gastrointestinal surgery or other procedures that might, in the opinion of the investigator, interfere with the absorption or swallowing of the study drugs Exclusion Criteria for Maintenance Therapy: - >= grade 2 peripheral neuropathy within 14 days before beginning maintenance therapy - Prolonged QTC - Poorly controlled diabetes mellitus (DM) - Myocardial infarction (MI) with ASCT or developed dilated cardiomyopathy with ASCT - Untreated systemic infection - Potassium (K) and magnesium (Mg) < normal limits of adequate supplementation - Patient had MI within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any ECG abnormality at screening must be documented by the investigator as not medically relevant - Patient has hypersensitivity to VELCADE, boron, or mannitol - Female subject is pregnant or lactating; confirmation that the subject is not pregnant must be established by a negative serum beta-hCG pregnancy test result obtained during screening; pregnancy testing is not required for postmenopausal or surgically sterilized women - Female patients who are lactating or have a positive serum pregnancy test during the screening period, or a positive urine pregnancy test on Day 1 before first dose of study drug, if applicable - Serious medical or psychiatric illness likely to interfere with participation in this clinical study - Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy - Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and throughout the duration of this trial - Radiation therapy within 3 weeks before randomization; enrollment of subjects who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 3 weeks have elapsed since the last date of therapy Other exclusion criteria may apply. b9bd568aa74705bb91b3c24a4e311176 7858 Donor Peripheral Blood Stem Cell Transplant and Pretargeted Radioimmunotherapy in Treating Patients With High-Risk Advanced Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Myelodysplastic Syndrome I John Pagel, MD, PhD 2309.00 1; 2; 11; 36; 43; 61 Acute Lymphoid Leukemia (ALL); Acute Myeloid Leukemia (AML); Bone Marrow and Hematopoietic Stem Cell Transplant (BMT and HSCT); Hematologic Malignancies; Leukemia; Myelodysplastic and Myeloproliferative Syndromes (MDS and MPD) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.7858.html http://www.clinicaltrials.gov/ct/search?term=NCT00988715 NCT00988715 This phase I trial uses pretargeted radioimmunotherapy and donor peripheral blood stem cell transplant employing fludarabine phosphate and total-body irradiation (TBI) to treat patients with high-risk acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome. Giving chemotherapy drugs, such as fludarabine phosphate, and TBI before a donor peripheral blood stem cell transplant helps stop the patient's immune system from rejecting the donor's stem cells. Radiolabeled monoclonal antibodies can be combined with fludarabine phosphate and TBI to find cancer cells and kill them without harming normal cells. Pretargeted radioimmunotherapy (PRIT) allows for further improved targeting of tumor cells over standard directly labeled antibodies. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Patients with advanced AML or ALL defined as beyond first remission, primary refractory disease, or evolved from myelodysplastic or myeloproliferative syndromes; or patients with MDS expressed as refractory anemia with excess blasts (RAEB), refractory cytopenia with multilineage dysplasia (RCMD), RCMD with ringed sideroblasts (RCMD-RS), or chronic myelomonocytic leukemia (CMML) - Patients not in remission must have CD45-expressing leukemic blasts; patients in remission do not require phenotyping and may have leukemia previously documented to be CD45 negative (because in remission patients, virtually all antibody binding is to nonmalignant cells which make up >= 95% of nucleated cells in the marrow) - Patients should have a circulating blast count of less than 10,000/mm^3 (control with hydroxyurea or similar agent is allowed) - Patients must have an estimated creatinine clearance greater than 50/mL per minute (test must be performed within 28 days prior to registration) - Bilirubin < 2 times the upper limit of normal - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2 times the upper limit of normal - Karnofsky score >= 70 or Eastern Cooperative Oncology Group (ECOG) =< 2 - Patients must have an expected survival of > 60 days and must be free of active infection - Patients must have an human leukocyte antigen (HLA)-identical sibling donor or an HLA-matched unrelated donor who meets standard Seattle Cancer Care Alliance (SCCA) and/or National Marrow Donor Program (NMDP) criteria for peripheral blood stem cell (PBSC) donation; related donors should be matched by molecular methods at the intermediate resolution level at HLA-A, B, C, and DRB1 according to Fred Hutchinson Cancer Research Center (FHCRC) Standard Practice Guidelines and to the allele level at DQB1; unrelated donors should be identified using matching criteria that follows the FHCRC standard practice guidelines limiting the study to eligible donors that are allele matched for HLA-A, B, C, DRB1, and DQB1 (Grade 1), and accepting up to one allele mismatch as per standard practice grade 2.1 for HLA-A, B, or C; PBSC is the only permitted stem cell source Other eligibility criteria may apply. - Circulating human anti-mouse antibody (HAMA) or human anti-streptavidin antibody (HASA) - Prior radiation to maximally tolerated levels to any critical normal organ - Patients may not have symptomatic coronary artery disease and may not be on cardiac medications for anti-arrhythmic or inotropic effects - Patients with the following organ dysfunction: - a) Left ventricular ejection fraction < 35% - b)Corrected diffusion capacity of carbon monoxide (DLCO) < 35% and/or receiving supplemental continuous oxygen - c)Liver abnormalities: fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction as evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis, or symptomatic biliary disease - Patients who are known seropositive for human immunodeficiency virus (HIV) - Perceived inability to tolerate diagnostic or therapeutic procedures, particularly treatment in radiation isolation - Active central nervous system (CNS) leukemia - Women of childbearing potential who are pregnant (beta-human chorionic gonadotropin [b-HCG] +)or breast feeding - Fertile men and women unwilling to use contraceptives during and for 12 months post transplant - Patients may not use vitamin supplements containing biotin from the time of 1 week prior to treatment until 1 week after completion of treatment with all PRIT components - Inability to understand or give an informed consent Other exclusion criteria may apply. a20d43df2a1bf146a3a3f84ceab2c910 8047 Rituximab, Combination Chemotherapy, Filgrastim (G-CSF), and Plerixafor in Treating Patients With Non-Hodgkin Lymphoma Undergoing Mobilization of Autologous Peripheral Blood Stem Cells II Leona Holmberg, MD, PhD 2310.00 15; 36; 48; 64 Burkitt's Lymphoma; Hematologic Malignancies; Lymphoma; Non-Hodgkin's Lymphoma (NHL) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8047.html http://www.clinicaltrials.gov/ct/search?term=NCT01097057 NCT01097057 This phase II trial is studying how well giving rituximab, ICE combination chemotherapy, and G-CSF together with plerixafor works in treating patients with non-Hodgkin lymphoma undergoing mobilization of autologous peripheral blood stem cells. Giving chemotherapy (ICE) with monoclonal antibodies, such as rituximab, stops the growth of cancer cells by stopping them from dividing or by killing them and helps get better autologous stem cell product. Giving colony-stimulating factors, such as filgrastim (G-CSF), and plerixafor helps stem cells move from the patient's bone marrow to the blood so they can be collected and stored for future autologous transplant Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Diagnosis of CD20+ non-Hodgkin's lymphoma - Cardiac: left ventricular ejection fraction at rest >= 50% demonstrated by MUGA or echocardiogram - Hepatic: bilirubin =< 2.0 mg/dL (except for isolated hyperbilirubinemia attributed to Gilbert syndrome) and ALT and AST =< 3 times the upper limit of normal - Renal: creatinine clearance (calculated creatinine clearance is permitted) > 50 mL/min - Signed informed consent - Planned autologous transplant within 3 months after collection of PBSCs Other eligibility criteria may apply. - -Karnofsky performance score < 70% - Uncontrolled bacterial, viral, or fungal infection (currently taking medication and with progression or no clinical improvement) - Prior other malignancies except resected basal cell carcinoma or treated cervical carcinoma or breast cancer in situ; cancer treated with curative intent > 5 years previously will be allowed - Pregnant or breastfeeding - Fertile men or women unwilling to use contraceptive techniques from the time of chemo-mobilization - Prior autologous or allogeneic HSCT - HIV positive - Plan to be treated on another investigational therapy within 4 weeks of enrolling on this study - Hepatitis B carriers Other exclusion criteria may apply. 4885188f020608d21984d35d01c997e9 7688 Montelukast to Treat Bronchiolitis Obliterans II Paul Martin, MD 2317.00 96 Chronic Graft Versus Host Disease (cGVHD) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.7688.html http://www.clinicaltrials.gov/ct/search?term=NCT00656058 NCT00656058 Purpose Background: Bronchiolitis obliterans is a form of chronic graft-versus-host disease (GVHD) that sometimes develops after stem cell transplantation (SCT) or bone marrow transplantation (BMT). In bronchiolitis obliterans, immune cells that normally fight infections attack the lungs of the transplant recipient, causing destruction of lung tissue and fibrosis (scarring). When fibrosis develops, the lungs cannot work properly. Montelukast (Singulair) is a drug that has been used for many years to treat asthma. Its use as a treatment for bronchiolitis obliterans is experimental. Objectives: To see if montelukast improves or stabilizes lung function in patients who develop bronchiolitis obliterans after BMT or SCT. To assess the safety of montelukast in patients with bronchiolitis obliterans after BMT or SCT To see if montelukast affects the cells that damage the lungs. To see if montelukast improves other forms of chronic GVHD, quality of life, and overall survival in patients with bronchiolitis obliterans after BMT or SCT. Ages Eligible for Study: 6 Years to 80 Years Genders Eligible for Study: Both - Age greater than 6 years old. - Diagnosis of bronchiolitis obliterans after allogeneic or autologous stem cell transplant. The criteria will be based on the definitions created by the NIH consortium on cGVHD. As part of these criterion, for patients without pathologic evidence of BO, one other sign of chronic GVHD must be present. For diagnosis of cGVHD, a minimum of the following must be present: 1) a process distinct from that diagnosed as acute GVHD, 2) the presence of a diagnostic sign or a distinctive sign supported by another clinical or laboratory test, and 3) the exclusion of other pathologies (i.e. recurrent cancer, drug reaction or infection (see Appendix 5a for a list of diagnostic signs.). To meet criteria for a diagnosis of bronchiolitis obliterans, patients must fulfill all 3 criteria. Prior lung tissue biopsy will be analyzed and confirmed to show evidence of bronchiolitis obliterans by the NCI Laboratory of Pathology if available. If tissue is not available for confirmation, a new biopsy will not be performed. - For bronchiolitis obliterans: 1. FEV1 less than or equal to 75 percent of predicted by pulmonary function evaluation for height and weight. 2. Evidence of air-trapping or small airway thickening or bronchiectasis on high resolution chest CT and RV or RV/FVC greater than 120 percent and evidence of chronic GVHD of another organ, OR FEV1/ vital capacity (slow or forced VC whichever is larger) ratio less than 5 percent of predicted for age or less than 0.7, OR pathologic evidence of bronchiolar inflammation and obstruction of the lumen consistent with a diagnosis of BO. Pulmonary function tests will utilize body plethysmography not helium studies for pertinent values when there is a discrepancy if available. 3. Absence of active infection with appropriate investigation of any clinical symptoms to include radiographic, microbiologic, and pathologic studies as determined by the PI or LAI. Patients must also have 2 PFT measurements with documented FEV1 values greater than 3 months apart to calculate the entry FEV1 slope. All available prior PFTs will be utilized for baseline slope calculation. For adult patients, the absolute FEV1 will be utilized for slope calculation; for pediatric patients, the percent predicted will be used. For patients enrolled after an acute decline following BMT without 2 post-BMT values greater than 3 months apart, the pre-BMT value may be utilized as the first value and the entry PFT value may be the second for the slope calculation. The baseline and 6th-cycle PFT should be done at the accruing site. Prior therapy: For patients with a chronic diagnosis of BO who have been on treatments, any prior therapy that has been administered chronically for > 3 months will be acceptable for enrollment as long as the patient has not demonstrated consistent improvement attributed to these agents in a one month (or more) period of observation preceding enrollment. For patients on steroids, a steroid burst exceeding and increase of one half mg/kg/day will be considered for the start of the 3 month monitoring period. Notably, documented intercurrent infections that are treated with antimicrobials that result in improvements to, but not above previous baselines will not be considered an improvement attributable to immunosuppressive therapy. Patients who have had consistent improvements in the months preceding trial entry will not be eligible since there will be no way to discern improvement due to montelukast versus another therapy. Alternatively, a patient with a new diagnosis of bronchiolitis obliterans characterized by a new decrease in FEV1 is also eligible for this study. Notably, patients who have received bronchodilators or other pulmonary therapies may be included in this study as long as montelukast is not part of this regimen. Performance status: Karnofsky or Lansky performance status greater than or equal to 40 percent (Appendix 1). Ability to give informed consent. For patients less than 18 years of age, their legal guardian must give informed consent. Pediatric patients will be included in an age appropriate discussion in accordance with NIH guidelines or participating institutional guidelines. Hepatic function: Patients must have evidence of adequate liver function prior to enrollment defined by total bilirubin less than 3 times the upper limit of normal and transaminases less than 5 times the upper limit of normal for age appropriate indices. Cardiac function: Patients must have evidence of adequate cardiac function prior to enrollment defined by ejection fraction greater than 25 percent performed within the last 6 months at NIH and absence of symptoms of cardiac disease at FHCRC, JHH, or Hackensack. Pulmonary function: Patients must have an FEV1 greater than or equal to 20 percent predicted for inclusion in this study. Other eligibility criteria may apply. - Underlying disease status: Patients with tumor burden greater than minimal residual disease (i.e. tumor burden that can only be detected by molecular methods) would be excluded from this study. - Prior post-transplant treatment with montelukast or zakirlukast within the past 2 months and total duration of therapy does not exceed 3 months. - Clinically significant systemic illness with manifestations of significant organ dysfunction which in the judgment of Principal or Associate Investigator would render the patient unlikely to tolerate the protocol therapy or complete the study. - Patients must have been on their current cGVHD therapeutic regimen for at least 3 months with stable or decreasing FEV1 to be eligible for this trial. Any patient who has been on a therapy for less than 3 months for cGVHD will need to be monitored for 3 months without improvement in FEV1 prior to enrollment. - Ventilated patients are excluded. - Patients taking rifampin or phenobarbital as these medications alter the metabolism of montelukast. - Patients taking greater than one age-appropriate dose of ibuprofen or aspirin containing products per day that inhibit cyclooxygenase will be excluded from this trial. The acceptable upper limit for adult daily doses of aspirin is 650mg/day and 800mg/day of ibuprophen. For children, the acceptable upper limit of ibuprophen is pediatric dose per day (less than 10 mg per kg to a maximum of 800 mg). Children should not take aspirin due to risk of Reye's syndrome unless specifically prescribed by their physician. - Patients with a history of allergy to montelukast. - Pregnant females and nursing mothers will be excluded from this trial due to unknown risks to the developing fetus. While on study, patients of child-bearing potential must be able to consent to utilize effective birth control measures. Other exclusion criteria may apply. ea303cc8b84ce50e111e1742243b2ac7 7682 Cyclosporine Eye Drops in Preventing Graft-Versus-Host Disease of the Eye in Patients Who Have Undergone Donor Stem Cell Transplant for Hematologic Cancer or Bone Marrow Failure Disorder III Mary Flowers, MD 2321.00 43; 48; 96 Leukemia; Lymphoma; Chronic Graft Versus Host Disease (cGVHD) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.7682.html http://www.clinicaltrials.gov/ct/search?term=2321.00 2321.00 RATIONALE: Cyclosporine eye drops may prevent graft-versus-host disease of the eye in patients who have undergone donor stem cell transplant for hematologic cancer or bone marrow failure disorder. PURPOSE: This randomized phase I trial is studying how well cyclosporine eye drops work in preventing graft-versus-host disease of the eye in patients who have undergone donor stem cell transplant for hematologic cancer or bone marrow failure disorder. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Age greater than or equal to 18 years at time of enrollment - Day 80-120 after first allogeneic stem cell transplant for hematologic malignancies or -marrow failure disorder at time of study enrollment - Signed informed consent - Willing to adhere to protocol requirements Other eligibility criteria may apply. - history of non-compliance - diagnosis of ocular GVHD at time of study enrollment - documented dry eye prior to onset of stem cell transplant - significant non- GVHD ocular problems that precludes participation in study - life expectancy of lesser than 6 months at time of enrollment (viz. grade 4 acute GVHD, florid progression or relapse of underlying disease) - history of documented ocular infections prior to stem cell transplant or during transplant (i.e. history of herpetic keratitis) - females who are pregnant or breastfeeding Other exclusion criteria may apply. 2202e4d059e61bc7e3c5327f8c32a1f0 7760 Imatinib and Rituximab in Treating Cutaneous Sclerosis in Patients With Chronic Graft-Versus-Host Disease II Mary Flowers, MD 2343.00 96 Chronic Graft Versus Host Disease (cGVHD) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.7760.html http://www.clinicaltrials.gov/ct/search?term=NCT01309997 NCT01309997 This randomized phase II trial is evaluating how well imatinib mesylate works compared to rituximab in treating cutaneous sclerosis in patients with chronic graft- versus-host disease (GVHD). Both imatinib and rituximab have been reported to decrease skin thickening and improve skin and joint flexibility in people with cutaneous sclerosis due to chronic GVHD Ages Eligible for Study: 2 Years and older Genders Eligible for Study: Both - Cutaneous sclerosis after hematopoietic cell transplant (HCT) diagnosed no more than 18 months before study enrollment with sclerotic skin, morphea, myofascial involvement or joint contractures with a score of 2 or greater on the Vienna skin scale in any area, or a score of 5 or less at the shoulder, elbow or wrist, or a score of 3 or less at the ankle on the range-of-motion (ROM) assessment - Stable doses of systemic immunosuppressive medications for a minimum of 4 weeks prior to the date of consent - Receiving corticosteroids at a dose greater than required for treatment of adrenal insufficiency, unless the physician documents why steroids are contraindicated - Age 2-99 years - Karnofsky performance status >= 60% at enrollment - All females of childbearing potential must have a negative serum or urine pregnancy test =< 7 days prior to starting study therapy - All females of childbearing potential must agree to use a form of Food and Drug Administration (FDA) approved contraception from enrollment to one month after study treatment ends - Subject has the ability to understand and willingness to sign a written informed consent document Other eligibility criteria may apply. - Total bilirubin > 1.5x upper limit of normal (ULN) - Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x ULN - Renal insufficiency (serum creatinine > 2.0 mg/dl) - Platelets < 30,000/ul or absolute neutrophil count < 1500/ul - Known hypersensitivity to Rituximab or other anti-B cell antibodies - Known Imatinib intolerance or allergy - Evidence of any active viral, bacterial, or fungal infection that is progressive despite appropriate treatment - Known hepatitis B surface antigen positive - Pregnant, lactating, or planning a pregnancy while in the study - Distal extremity skin score 3 or higher as the only manifestation of sclerosis - Treatment of chronic GVHD with either Imatinib or Rituximab, or receipt of Imatinib or Rituximab within the previous 6 months for any other indication - History of psychiatric disorder that would interfere with normal participation in this study - Inability or unwillingness of subject and/or parent guardian to provide informed consent or comply with study protocol - Use of non-FDA approved drugs within 4 weeks of participation - Patient with any condition that, in the opinion of the investigator, would interfere with the subject's ability to comply with the study requirements - Patients with uncontrolled substance abuse - Current treatment with sirolimus (patients may stop sirolimus on the day of enrollment; if randomized to imatinib, they should wait seven days before starting the study drug) Other exclusion criteria may apply. 6b5c84bcdb2aa779b4c65fd844df1b0f 9247 Monoclonal Antibody Therapy Before Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoid Malignancies I Ajay Gopal, MD 2361.00 36; 48; 64 Hematologic Malignancies; Lymphoma; Non-Hodgkin's Lymphoma (NHL) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9247.html http://www.clinicaltrials.gov/ct/search?term=NCT01678443 NCT01678443 This phase I trial studies the side effects and best dose of monoclonal antibody therapy before stem cell transplant in treating patients with relapsed or refractory lymphoid malignancies. Radiolabeled monoclonal antibodies, such as yttrium- 90 anti-CD45 monoclonal antibody BC8, can find cancer cells and carry cancer-killing substances to them without harming normal cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Giving radiolabeled monoclonal antibody before a stem cell transplant may be an effective treatment for relapsed or refractory lymphoid malignancies Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Patients must have a histologically confirmed diagnosis of B-NHL, T-NHL, or HL; CD45 antigen expression must be documented on tumor specimens in all cases except HL, in whom histologic demonstration of CD45+ cells adjacent to the Reed Sternberg cells is required; patients must have received at least one prior standard systemic therapy with documented recurrent or refractory disease; patients with mantle cell lymphoma (MCL), T-NHL, or other high-risk malignancies may be enrolled/transplanted in complete remission (CR)/first partial remission (PR1) - Creatinine < 2.0 - Bilirubin < 1.5 mg/dL - All patients eligible for therapeutic study must have a minimum of >/= 2 x10^6 CD34/kg autologous hematopoietic stem cells harvested and cryopreserved - Patients must have an expected survival of > 60 days and must be free of major infection - Patients are preferred to have either a tumor mass amenable to core needle biopsy during the dosimetry phase, or a measurable tumor mass with at least one site of involvement measuring 2.5 cm in largest dimension on computed tomography (CT) imaging for purposes of planar and/or single-photon emission computed tomography (SPECT)/CT tumor dosimetry Other eligibility criteria may apply. - Circulating human anti-mouse antibody (HAMA), to be determined before each infusion - Systemic anti-lymphoma therapy given in the previous 30 days before the scheduled therapy dose with the exception of rituximab - Inability to understand or give an informed consent - Lymphoma involving the central nervous system - Other serious medical conditions considered to represent contraindications to ASCT (e.g., abnormally decreased cardiac ejection fraction, diffusion capacity of the lung for carbon monoxide [DLCO] < 50% predicted, acquired immune deficiency syndrome [AIDS], etc.) - Known human immunodeficiency virus (HIV) seropositivity - Pregnancy or breast feeding - Prior allogeneic bone marrow or stem cell transplant - Prior autologous bone marrow or stem cell transplant within 1 year of enrollment - Prior radiation therapy (RT) > 20 Gray (Gy) to a critical organ within 1 year of enrollment - Southwest Oncology Group (SWOG) performance status >/= 2.0 - Patients with relapsed diffuse large B-cell lymphoma (DLBCL) or HL that have achieved a positron emission tomography (PET)-negative CR following first salvage chemotherapy Other exclusion criteria may apply. 0bf278a5267185da8eb4554388cf80b6 8027 Chronic Graft-versus-Host Disease Treatment II/III Paul Carpenter, MD 2375.00 11 Bone Marrow and Hematopoietic Stem Cell Transplant (BMT and HSCT) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8027.html http://www.clinicaltrials.gov/ct/search?term=NCT01106833 NCT01106833 Purpose: This study is designed as a combined Phase II/III, randomized, open label, multicenter, prospective comparative study of sirolimus plus prednisone, sirolimus/extracorporeal photopheresis plus prednisone versus sirolimus/calcineurin-inhibitor plus prednisone for the treatment of chronic GVHD. Patients will be stratified by transplant center and will be randomized to one of the two pre-specified experimental arms (Sirolimus + prednisone, Sirolimus + ECP + prednisone) or the comparator arm (Sirolimus + calcineurin inhibitor + prednisone) in a 1:1 ratio. Genders Eligible for Study: Both - Suitable candidates are patients with chronic GVHD that is: a)High-risk (Platelets less than 100,000, greater than 50% skin involvement, bronchiolitis obliterans, or already being treated with prednisone greater than 0.5 mg/kg/day for a history of acute GVHD), newly diagnosed or not responding after up to 12 weeks of therapy with prednisone ± CNI ± an additional agent; b)Standard-risk and deemed inadequately responding after up to 12 weeks of therapy that began with prednisone at 0.5-1 mg/kg/day ± CNI; c) Inadequately responding to therapy with prednisone or sirolimus alone, or prednisone and ECP alone. - Classic chronic GVHD with or without overlap syndrome but not late persistent or recurrent acute GVHD alone, diagnosed according to the NIH Consensus Working Group Guidelines and which requires treatment with systemic immunosuppressive medication. - Weight more than or equal to 25 kg - Patient or guardian willing and able to provide informed consent. - Stated willingness to use contraception in women of childbearing potential. - Stated willingness of patient to comply with study procedures and reporting requirements. Other eligibility criteria may apply. - Inability to begin prednisone therapy at a dose of greater than 0.5 mg/kg/day. - Already receiving therapy with prednisone, sirolimus and CNI. - Invasive fungal or viral infection not responding to appropriate antifungal or antiviral therapies. - Inadequate renal function defined as measured creatinine clearance less than 50 mL/min/1.73 m^2 based on the Cockcroft-Gault formula (adults) or Schwartz formula (age < 12 years). Adults: eCCr (mL/min/1.73 m^2) = (140 - age) x mass (kg) x (0.85 if female)/72 x serum creatinine (mg/dL; Children: eCCr (mL/min/1.73 m^2) = k x height (cm) / serum creatinine (mg/dL) k = 0.33 (pre-term), 0.45 (full term to 1 year old), 0.55 (age 1-12 years). - Inability to tolerate oral medications. - Absolute neutrophil count < 1500 per microliter. - Requirement for platelet transfusions other than to perform extracorporeal photopheresis. - Pregnancy. - Progressive or recurrent malignancy defined other than by quantitative molecular assays. - Known hypersensitivity to sirolimus. Other exclusion criteria may apply. 8870b46ccdf265ecb2845c921e32f96d 8769 High-Dose Y-90-Ibritumomab Tiuxetan Added to Reduced-Intensity Allogeneic Stem Cell Transplant Regimen for Relapsed or Refractory Aggressive B-Cell Lymphoma II Ajay Gopal, MD 2398.00 15; 36; 38; 48; 64 Burkitt's Lymphoma; Hematologic Malignancies; Hodgkin's Lymphoma; Lymphoma; Non-Hodgkin's Lymphoma (NHL) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8769.html http://www.clinicaltrials.gov/ct/search?term=NCT01434472 NCT01434472 This phase II trial studies the side effects and how well giving high-dose yttrium-90 (Y-90)-ibritumomab tiuxetan (anti-CD20) followed by fludarabine phosphate, low-dose total body irradiation (TBI), and donor peripheral blood stem cell transplant (PBSCT) works in treating patients with relapsed or refractory aggressive B-cell lymphoma. Radiolabeled monoclonal antibodies, such as Y-90-ibritumomab tiuxetan, can find cancer cells and carry cancer-killing substances to them with less effect on normal cells. Giving chemotherapy, such as fludarabine phosphate, and TBI before a donor PBSCT helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. However, high-dose radiolabeled antibodies also destroy healthy blood cells in the patient's body. When healthy stem cells from a donor are infused into the patient (stem cell transplant), they may help the patient's body replace these blood cells. Giving high-dose Y-90-ibritumomab tiuxetan followed by fludarabine phosphate, TBI, and donor PBSCT may be an effective treatment for patients with B-cell lymphoma Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Patients must have a histologically confirmed diagnosis of aggressive B-cell lymphoma (diffuse large B-cell lymphoma [DLBCL], Burkitt lymphoma [BL], etc.) expressing the CD20 antigen and have failed at least one prior standard systemic therapy - Patients must have relapsed after high-dose therapy and autologous transplantation or be ineligible for high-dose therapy and autologous transplantation; patients that have failed autologous transplantation are those with persistent disease > 30 days after transplant; those ineligible for autologous transplant include those with chemoresistant disease (i.e., patients who have not achieved a partial response or better with their most recent chemotherapy regimen), are expected to have a poor outcome from autologous transplant (e.g., DLBCL relapsing within one year of R-CHOP, double hit lymphoma, MYC+ lymphoma, persistent PET positivity after chemotherapy), are unable to collect sufficient or tumor-free autologous stem cells per Seattle Cancer Care Alliance (SCCA) standard practice, are unable to tolerate the high-dose autologous conditioning regimens, or who refuse a high-dose autologous transplant regimen - Creatinine (Cr) < 2.0 - Bilirubin < 1.5mg/dL with the exception of patients thought to have Gilbert's syndrome, who may have a total bilirubin above 1.5mg/dL - Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 3 x upper limit of normal (ULN) - Patients must have an expected survival without treatment of > 60 days and must be free of major infection including human immunodeficiency virus (HIV) - Patients must have an HLA-identical related or HLA-matched unrelated donor - Patients must be = or > 18 years old Other eligibility criteria may apply. - Systemic anti-lymphoma therapy given within 30 days prior to therapeutic 90Y-ibritumomab tiuxetan dose - Inability to understand or give an informed consent - Central nervous system lymphoma - Pregnancy - Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment - Southwest Oncology Group (SWOG)/Eastern Cooperative Oncology Group (ECOG) performance score >= 2 - High-dose chemotherapy or external beam radiation therapy to lung, liver, or kidneys > 20 Gy within the previous 100 days prior to therapeutic 90Y-ibritumomab tiuxetan dose - Medical condition that would contraindicate allogeneic transplantation as per standard practice guidelines (e.g., impaired cardiopulmonary function, hepatitis, etc) - Altered biodistribution (determined following trace-labeled 111In-ibritumomab tiuxetan dose) Other exclusion criteria may apply. 179adb8882a03a3aa621a6c5ae3024bc 8464 Clofarabine and Low-Dose Total-Body Irradiation in Treating Patients With Acute Myeloid Leukemia Undergoing Donor Peripheral Blood Stem Cell Transplant II Boglarka Gyurkocza, MD 2430.00 2; 36; 43 Acute Myeloid Leukemia (AML); Hematologic Malignancies; Leukemia Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8464.html http://www.clinicaltrials.gov/ct/search?term=NCT01252667 NCT01252667 This phase II trial is studying the side effects and how well giving clofarabine together with low-dose total-body irradiation (TBI) works in treating patients with acute myeloid leukemia (AML) undergoing donor peripheral blood stem cell transplant (PBSCT). Giving chemotherapy and TBI before a donor PBSCT helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Ages Eligible for Study: 1 Year and older Genders Eligible for Study: Both - Patients age >= 55 years with AML OR patients age < 55 years with AML, who also through pre-existing medical conditions or prior therapy are considered to be at high risk for serious toxicities associated with a conventional, high-dose preparative regimen - Patients must be in morphologic leukemia-free state (marrow blasts < 5%) without evidence of extramedullary disease within 21 days of HCT - Only patients with Relapse Risk Score > 0 ("high risk") will be enrolled during Part 1; patients with all Relapse Risk Scores will be enrolled during Part 2 - HLA-identical related or HLA-matched unrelated donor available - A signed informed consent form or minor assent form - Patients treated at the Fred Hutchinson Cancer Research Center (FHCRC), with actual body weight > 15 kg will be eligible for clofarabine pharmacokinetic studies; participation in pharmacokinetic studies will be optional and will be offered to patients at the time of enrollment - DONOR: FHCRC matching allowed will be Grade 1.0 to 2.1: unrelated donors who are prospectively: matched for HLA-A, B, C, DRB1 and DQB1 by high resolution typing; only a single allele disparity will be allowed for HLA-A, B, or C as defined by high resolution typing - DONOR: A positive anti-donor cytotoxic crossmatch is an absolute donor exclusion; donors are excluded when preexisting immunoreactivity is identified that would jeopardize donor hematopoietic cell engraftment; this determination is based on the standard practice of the individual institution; the recommended procedure for patients with 10 of 10 HLA allele level (phenotypic) match is to obtain a panel reactive antibody (PRA) screens to class I and class II antigens for all patients before HCT; if the PRA shows > 10% activity, then flow cytometric or B and T cell cytotoxic cross matches should be obtained; the donor should be excluded if any of the cytotoxic cross match assays are positive; for those patients with an HLA Class I allele mismatch, flow cytometric or B and T cell cytotoxic cross matches should be obtained regardless of the PRA results - DONOR: Patient and donor pairs homozygous at a mismatched allele are considered a two-allele mismatch, i.e., the patient is A*0101 and the donor is A*0102, and this type of mismatch is not allowed - DONOR: Peripheral blood stem cells (PBSC) only will be permitted as a HSC source on this protocol Other eligibility criteria may apply. - AML French-American-British (FAB) M3 in first complete remission (CR1) - Active AML involvement of the central nervous system (CNS) with disease refractory to intrathecal chemotherapy - Presence of circulating leukemic blasts in the peripheral blood detected by standard morphology - Patients who are human immunodeficiency virus (HIV)+ (HIV+ patients registered at Fred Hutchinson Cancer Research Center [FHCRC] should be offered treatment on Protocol 1410) - Fertile men and women unwilling to use contraceptive techniques during and for 12 months following treatment - Left ventricular ejection fraction < 35% (or, if unable to obtain ejection fraction, shortening fraction of < 26%); ejection fraction is required if age > 50 years or there is a history of anthracycline exposure or history of cardiac disease; patients with a shortening fraction < 26% may be enrolled if approved by a cardiologist - Diffusion capacity of the lung for carbon monoxide (DLCO) < 40% (corrected), total lung capacity (TLC) < 40%, forced expiratory volume in one second (FEV1) < 40% and/or receiving supplementary continuous oxygen - The FHCRC Principal Investigator (PI) of the study must approve enrollment of all patients with pulmonary nodules - Patients with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, and the degree of portal hypertension; patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bridging fibrosis, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3mg/dL, or symptomatic biliary disease - Serum creatinine should be within normal limits as specified by institutional guidelines; for patients with serum creatinine > upper limit of normal, a 24-hour creatinine clearance will be performed and should be equal to or more than the lower limit of normal - Karnofsky score < 60 or Lansky Score < 50 - Patients with poorly controlled hypertension and on multiple antihypertensives - Females who are pregnant or breastfeeding - Patients with active non-hematologic malignancies (except non-melanoma skin cancers) or those with non-hematologic malignancies (except non-melanoma skin cancers) who have been rendered with no evidence of disease, but have a greater than 20% chance of having disease recurrence within five years; this exclusion does not apply to patients with non-hematologic malignancies that do not require therapy - The addition of cytotoxic agents for "cytoreduction" with the exception of tyrosine kinase inhibitors (such as imatinib mesylate), cytokine therapy, hydroxyurea, low dose cytarabine, chlorambucil, or Rituxan will not be allowed within three weeks of the initiation of conditioning - Fungal infections with radiological progression after receipt of amphotericin B or active triazole for greater than 1 month - Patients with active bacterial or fungal infections unresponsive to medical therapy - DONOR: Marrow donors - DONOR: Donors who are HIV-positive and/or medical conditions that would result in increased risk to the donor filgrastim (G-CSF) mobilization and PBSC collections - DONOR: Identical twin - DONOR: Any contraindication to the administration of subcutaneous G-CSF at a dose of 16 mg/kg/day for 5 consecutive days - DONOR: Serious medical or psychological illness - DONOR: Pregnant or lactating females - DONOR: Prior malignancy within the preceding 5 years, with the exception of non-melanoma skin cancers - DONOR: Children < 12 years old Other exclusion criteria may apply. 7436bf22ad29ae3acdfe84d7fedeeb44 8404 Stem Cell Transplant With Lenalidomide Maintenance in Patients With Multiple Myeloma (BMT CTN 0702) III Bill Bensinger, MD 2434.00 36; 57 Hematologic Malignancies; Multiple Myeloma (MM) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8404.html http://www.clinicaltrials.gov/ct/search?term=NCT01109004 NCT01109004 The study is designed as a Phase III, multicenter trial of tandem autologous transplants plus maintenance therapy versus the strategy of single autologous transplant plus consolidation therapy with lenalidomide, bortezomib and dexamethasone (RVD) followed by maintenance therapy or single autologous transplant plus maintenance therapy as part of upfront treatment of multiple myeloma (MM). Lenalidomide will be used as maintenance therapy for three years in all arms. Ages Eligible for Study: up to 70 Years Genders Eligible for Study: Both - Patients meeting the criteria for symptomatic multiple myeloma (MM). - Patients who are 70 years of age, or younger, at time of enrollment. - Patients who have received at least two cycles of any regimen as initial systemic therapy and are within 2 - 12 months of the first dose of initial therapy (this time frame excludes the time for mobilization therapy). - Patients must be able to receive high-dose melphalan within 8 weeks after the initiation of mobilization therapy whether delivered at the transplant center or at a referring center. - Cardiac function: left ventricular ejection fraction at rest greater than 40 percent. - Hepatic: bilirubin less than 2 times the upper limit of normal and ALT and AST less than 2.5 times the upper limit of normal. - Renal: Creatinine clearance of grater than or equal to 40 mL/min, estimated or calculated. - Pulmonary: DLCO, FEV1, FVC grater than 50 percent of predicted value (corrected for hemoglobin). - Patients with an adequate autologous graft defined as a cryopreserved PBSC graft containing greater than or equal to 4 x 10^6 CD34+ cells/kg patient weight. The graft may not be CD34+ selected or otherwise manipulated to remove tumor or other cells. The graft can be collected at the transplanting institution or by a referring center. The autograft must be stored so that there are two products each containing at least 2 x 10^6 CD34+ cells/kg patient weight. - Signed informed consent form. Other eligibility criteria may apply. - Patients who never fulfill the criteria for symptomatic MM. - Patients with purely non-secretory MM [absence of a monoclonal protein (M protein) in serum as measured by electrophoresis and immunofixation and the absence of Bence Jones protein in the urine defined by use of conventional electrophoresis and immunofixation techniques]. Patients with light chain MM detected in the serum by free light chain assay are eligible. - Patients with plasma cell leukemia. - Karnofsky performance score less than 70 percent. - Patients with greater than grade 2 sensory neuropathy (CTCAE). - Patients with uncontrolled bacterial, viral or fungal infections (currently taking medication and progression of clinical symptoms). - Patients seropositive for the human immunodeficiency virus (HIV). - Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant. - Patient has hypersensitivity to bortezomib, boron or mannitol. - Patient has received other investigational drugs with 14 days before enrollment. - Patients with prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ or other cancer treated with curative intent greater than 5 years previously. Cancer treated with curative intent less than 5 years previously will not be allowed unless approved by the Protocol Officer or one of the Protocol Chairs. - Female patients who are pregnant (positive B-HCG) or breastfeeding. - Females of childbearing potential (FCBP) or men who have sexual contact with FCBP unwilling to use contraceptive techniques during the length of lenalidomide maintenance therapy. - Prior allograft or prior autograft. - Patients who have received mid-intensity melphalan (greater than 50 mg IV) as part of prior therapy. - Patients unable or unwilling to provide informed consent. - Prior organ transplant requiring immunosuppressive therapy. - Patients with disease progression prior to enrollment. - Patients who have received lenalidomide as initial therapy for MM and have experienced toxicities resulting in treatment discontinuation. - Patients who experienced thromboembolic events while on full anticoagulation during prior therapy with lenalidomide or thalidomide. - Patients unwilling to take DVT prophylaxis. Other exclusion criteria may apply. 7fddfa89b6adac5dc33e1de83899ac9c 8414 90 Y-BC8-DOTA Monoclonal Antibody, Fludarabine Phosphate, and Total-Body Irradiation Followed By Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Multiple Myeloma I Bill Bensinger, MD 2450.00 36; 57 Hematologic Malignancies; Multiple Myeloma (MM) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8414.html http://www.clinicaltrials.gov/ct/search?term=NCT01503242 NCT01503242 This phase I trial is studying the side effects and best dose of yttrium Y 90 anti-CD45 monoclonal antibody BC8 when given together with fludarabine phosphate and total-body irradiation followed by donor peripheral blood stem cell transplant in treating patients with multiple myeloma. Radiolabeled monoclonal antibodies, such as yttrium Y 90 anti-CD45 monoclonal antibody BC8, can find cancer cells and carry cancer-killing substances to them without harming normal cells. Giving chemotherapy drugs, such as fludarabine phosphate, and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells and helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving yttrium Y 90 anti-CD45 monoclonal antibody BC8, fludarabine phosphate, and total-body irradiation before the transplant together with cyclosporine and mycophenolate mofetil after the transplant may stop this from happening and may be an effective treatment for multiple myeloma Ages Eligible for Study: 18 Years to 65 Years Genders Eligible for Study: Both - Patients must have history of symptomatic myeloma requiring treatment (defined as significant anemia [hemoglobin (HgB) less than 10 gm/dl], renal dysfunction [creatinine greater than 2.0] not attributable to other causes, lytic bone disease on imaging, or hypercalcemia) and meet one of the following requirements: -- a) Have at least 1 high risk feature at diagnosis (including deletion 13 or hypodiploidy by conventional cytogenetics, t(4;14), t(14;16) or deletion 17 by fluorescence in situ hybridization [FISH], beta 2 microglobulin greater than 3.5, lactate dehydrogenase [LDH] greater than 1.5 x upper limit of normal [ULN]) (prior to chemotherapy); OR -- b) Have progressive disease on primary therapy with or without prior autologous stem cell transplant; OR -- c) Have persistent or progressive disease following autologous transplant; it is acceptable for these patients to have a second transplant for disease reduction - Bone marrow cellularity of at least 50 percent of normal by core biopsy (25% cellularity = 50% of normal) - Eastern Cooperative Oncology Group (ECOG) less than or equal to 2 - Measured creatinine clearance greater than 50 ml/min or estimated creatinine clearance greater than 50 ml/min - For females of childbearing potential, must have a negative pregnancy test - Patients must have an human leukocyte antigen (HLA)-identical sibling donor or an HLA-matched unrelated donor who meets standard Seattle Cancer Care Alliance (SCCA) and or National Marrow Donor Program (NMDP) criteria for peripheral blood stem cell (PBSC) donation, as follows: - a) Sibling donor: A patient and sibling donor should be matched for HLA-A, B, C, DRB1 and DQB1 by an intermediate resolution deoxyribonucleic acid (DNA)-based method - b) Unrelated donor: An unrelated donor and recipient should be typed by a high resolution DNA-based method, and ideally matched for HLA-A, B, C, DRB1 and DQB1 alleles, or if there is only a single locus disparity mismatched for an HLA-DQB1 antigen or allele; an unrelated donor may also be mismatched for any single ---1) one HLA-A, B or C antigen or allele, OR ---2) HLA-DRB1 allele (with or without matching for HLA-DQB1) - Ability to provide informed consent - DONOR: Patients must have an HLA matched donor as well as standard SCCA and or NMDP criteria for PBSC donation; donors must consent and be eligible to undergo GCSF mobilization and PBSC harvest; marrow is not allowed as a source of stem cells on this study Other eligibility criteria may apply. - Patients with the following organ dysfunction: - i) Left ventricular ejection fraction less than 35 percent - ii) Corrected diffusion capacity of carbon monoxide (DLCO) less than 35 percent or receiving supplemental continuous oxygen - iii) Liver abnormalities: fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction as evidences by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis, or symptomatic biliary disease - Pregnant or breast-feeding females - Circulating antibody against mouse immunoglobulin (HAMA) - Prior allogeneic transplant - Plasmacytomas greater than 1cm in marrow areas measured by magnetic resonance imaging (MRI) or extramedullary plasmacytomas (radiated lesions are exempt from this criteria); patients may receive cytoreductive therapy, including allogeneic stem cell transplant (ASCT) (if high risk) or second ASCT (if failed a prior ASCT) to achieve disease control - Prior radiation to maximally tolerated levels to any critical normal organ, or greater than 20 Gy prior radiation to large areas of the bone marrow (e.g., external radiation therapy to whole pelvis) - Patients who are known to be seropositive for human immunodeficiency virus (HIV) - Fertile men and women unwilling to use contraceptives during and for 12 months post-transplant Other exclusion criteria may apply. 40e99034de5dd40d4f691caa30bb05b4 8682 Lenalidomide With or Without Rituximab in Treating Patients With Progressive or Relapsed Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Prolymphocytic Leukemia, or Non-Hodgkin Lymphoma Previously Treated With Donor Stem Cell Transplant II Mohamed Sorror, MD, MSc 2467.00 18; 36; 43; 48; 64 Chronic Lymphoid Leukemia (CLL); Hematologic Malignancies; Leukemia; Lymphoma; Non-Hodgkin's Lymphoma (NHL) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8682.html http://www.clinicaltrials.gov/ct/search?term=NCT01419795 NCT01419795 This phase II trial studies how well giving lenalidomide with or without rituximab works in treating patients with progressive or relapsed chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), prolymphocytic leukemia (PLL), or non-Hodgkin lymphoma (NHL). Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving lenalidomide together with or without rituximab may kill more cancer cells Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Understand and voluntarily sign an informed consent form - Able to adhere to the study visit schedule and other protocol requirements - Patients with CLL/SLL/PLL or NHL and who: --- Met the criteria of relapse or progression after allogeneic HCT according to the HCT protocol or the attending discretion and who, --- Not responding to appropriate tapering of immunosuppressive medications - Absolute neutrophil count (ANC) >= 1500/mm^3 or > 1000/mm^3 if ANC has persistently < 1500/ mm^3 for more than 2 weeks - Platelet count (transfusion independent) >= 50,000/mm^3 or >= 20,000/mm^3 if platelet count has persistently < 50,000/mm^3 for more than 2 weeks - Creatinine clearance >= 30ml/min by Cockcroft-Gault formula - Total bilirubin =< 1.5 x upper limit of normal (ULN) or =< 3 x ULN if total bilirubin has been persistently > 1.5 x ULN for more than 2 weeks - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine transaminase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 3 x ULN or =< 5 x ULN if AST or ALT have been persistently > 3 x ULN for more than 2 weeks - Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days and again within 24 hours prior to prescribing lenalidomide for Cycle 1 (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy - All study participants must be registered into the mandatory RevAssist program, and be willing and able to comply with the requirements of RevAssist - Study participants with risk factors for venous thrombo-embolism (VTE), such as previous VTE, cardiac disease, chronic renal insufficiency, and/or poorly controlled diabetes, should be able to comply with some degree of prophylactic anticoagulation using aspirin 81 or 325 mg daily, coumadin, or low molecular weight heparin Other eligibility criteria may apply. - Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from signing the informed consent form - Pregnant or breast feeding females; (lactating females must agree not to breast feed while taking lenalidomide) - Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study - Known hypersensitivity to thalidomide - The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs - Resistance to prior use of lenalidomide, defined as progression on full dose lenalidomide within the first two cycles of therapy - Concurrent use of other anti-cancer agents or treatments - Known seropositive for or active viral infection with human immunodeficiency virus - Karnofsky performance status < 50% - Active grades III or IV acute graft-versus-host disease (GVHD) Other exclusion criteria may apply. 9bd70cab59589e8c7ae161014d3cc564 8580 Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8 Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia or Myelodysplastic Syndrome I John Pagel, MD, PhD 2468.00 2; 36; 43; 61 Acute Myeloid Leukemia (AML); Hematologic Malignancies; Leukemia; Myelodysplastic and Myeloproliferative Syndromes (MDS and MPD) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8580.html http://www.clinicaltrials.gov/ct/search?term=NCT01300572 NCT01300572 This phase I trial studies the side effects and maximum tolerated dose yttrium Y 90 anti-CD45 monoclonal antibody BC8 (90Y-BC8) followed by donor peripheral blood stem cell transplant (PBSC) in treating patients with high-risk acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Giving chemotherapy drugs, such as fludarabine phosphate (FLU), and total-body irradiation (TBI) before a donor PBSC transplant helps stop the growth of cancer or abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. Radiolabeled monoclonal antibodies, such as 90Y-BC8, can find cancer cells and carry cancer-killing substances to them without harming normal cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving FLU, 90Y-BC8, and TBI before the transplant together with cyclosporine and mycophenolate mofetil after the transplant may stop this from happening Ages Eligible for Study: 50 Years and older Genders Eligible for Study: Both - Patients must have advanced AML or high-risk MDS meeting one of the following descriptions: - a) AML beyond first remission (i.e., having relapsed at least one time after achieving remission in response to a treatment regimen) - b) AML representing primary refractory disease (i.e., having failed to achieve remission at any time following one or more prior treatment regimens) - c) AML evolved from MDS or myeloproliferative syndromes; or - d) MDS expressed as refractory anemia with excess blasts (RAEB) - Patients not in remission must have CD45-expressing leukemic blasts; patients in remission do not require phenotyping and may have leukemia previously documented to be CD45 negative (because in remission patients, virtually all antibody binding is to non-malignant cells which make up >= 95% of nucleated cells in the marrow) - Patients must be >=50 years of age - Patients should have a circulating blast count of less than 10,000/mm^3 (control with hydroxyurea or similar agent is allowed) - Patients must have an estimated creatinine clearance greater than 50/ml per minute - Bilirubin < 2 times the upper limit of normal (ULN) - Aspartate aminotransferase (AST) and alanine transaminase (ALT) < 2 times the upper limit of normal - Eastern Cooperative Oncology Group (ECOG) =< 2 - Patients must have an expected survival of > 60 days and must be free of active infection - Patients must have an human leukocyte antigen (HLA)-identical sibling donor or an HLA-matched unrelated donor who meets standard Seattle Cancer Care Alliance (SCCA) and/or National Marrow Donor Program (NMDP) criteria for PBSC donation, as follows: - a) Sibling donor; a patient and sibling donor should be matched for HLA-A, B, C, DRB1 and DQB1 by an intermediate resolution deoxyribonucleic acid (DNA)-based method - b) Unrelated donor; an unrelated donor and recipient should be typed by a high resolution DNA-based method, and ideally matched for HLA-A, B, C, DRB1 and DQB1 alleles, or if there is only a single locus disparity mismatched for an HLA-DQB1 antigen or allele; an unrelated donor may also be mismatched for any single 1) one HLA-A, B or C antigen or allele, or 2) HLA-DRB1 allele (with or without matching for HLA-DQB1) - DONOR: Donors must meet HLA matching criteria and standard SCCA and/or National Marrow Donor Program (NMDP) criteria for PBSC donation Other eligibility criteria may apply. - Circulating human anti-mouse antibody (HAMA) - Prior radiation to maximally tolerated levels to any critical normal organ, or > 20 Gy prior radiation to large areas of the bone marrow (e.g., external radiation therapy to whole pelvis) - Patients may not have symptomatic coronary artery disease and may not be on cardiac medications for anti-arrhythmic or inotropic effects - Left ventricular ejection fraction < 35% - Corrected diffusion lung capacity of carbon monoxide (DLCO) < 35% or receiving supplemental continuous oxygen - Liver abnormalities: fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction as evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis, or symptomatic biliary disease - Patients who are known to be seropositive for human immunodeficiency virus (HIV) - Perceived inability to tolerate diagnostic or therapeutic procedures - Active central nervous system (CNS) leukemia at time of treatment - Women of childbearing potential who are pregnant (beta-human chorionic gonadotrophin [HCG+]) or breast feeding - Fertile men and women unwilling to use contraceptives during and for 12 months post-transplant - Inability to understand or give an informed consent Other exclusion criteria may apply. 00e3aa80e73441a5d2edb912f12173bd 8590 Randomized Trial of Lenalidomide, Bortezomib, Dexamethasone vs High-Dose Treatment With SCT in MM Patients up to Age 65 (DFCI 10-106) III Bill Bensinger, MD 2477.00 36; 57 Hematologic Malignancies; Multiple Myeloma (MM) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8590.html http://www.clinicaltrials.gov/ct/search?term=NCT01208662 NCT01208662 The drugs, lenalidomide, bortezomib, and dexamethasone, are approved by the FDA. They have not been approved in the combination for multiple myeloma or any other type of cancer. Bortezomib is currently approved by the FDA for the treatment of multiple myeloma. Lenalidomide is approved for use with dexamethasone for patients with multiple myeloma who have received at least one prior therapy and for the treatment of certain types of myelodysplastic syndrome (another type of cancer affecting the blood). Dexamethasone is commonly used, either alone, or in combination with other drugs, to treat multiple myeloma. Melphalan and cyclophosphamide, the drugs used during stem cell collection and transplant, are also approved by the FDA. Melphalan is an FDA-approved chemotherapy for multiple myeloma and is used as a high-dose conditioning treatment prior to stem cell transplantation. Cyclophosphamide is used, either alone, or in combination with other drugs, to treat multiple myeloma. These drugs have been used in other multiple myeloma studies and information from those studies suggests that this combination of therapy may help to treat newly diagnosed multiple myeloma. In this research study, we are looking to explore the drug combination, lenalidomide, bortezomib and dexamethasone alone or when combined with autologous stem cell transplantation to see what side effects it may have and how well it works for treatment of newly diagnosed multiple myeloma. Specifically, the objective of this trial is to determine if, in the era of novel drugs, high dose therapy (HDT) is still necessary in the initial management of multiple myeloma in younger patients. In this study, HDT as compared to conventional dose treatment would be considered superior if it significantly prolongs progression-free survival by at least 9 months or more, recognizing that particular subgroups may benefit more compared to others. Ages Eligible for Study: 18 Years to 65 Years Genders Eligible for Study: Both - Diagnosis of Multiple Myeloma, according to the International Myeloma Foundation 2003 Diagnostic Criteria - Documented symptomatic myeloma, with organ damage related to myeloma with laboratory assessments performed within 21 days of registration - Myeloma that is measurable by either serum or urine evaluation of the monoclonal component or by assay of serum free light chains. - ECOG performance status </= 2 - Negative HIV blood test - Voluntary written informed consent Other eligibility criteria may apply. - Pregnant or lactating female - Prior systemic therapy for MM (localized radiotherapy allowed if >/= 2 weeks before study entry, corticosteroids allowed if dose </= equivalent of 160 mg dexamethasone over 2 weeks) - Primary amyloidosis (AL) or myeloma complicated by amylosis - Receiving any other investigational agents - Known brain metastases - Poor tolerability or allergy to any of the study drugs or compounds of similar composition - Platelet count <50,000/mm3, within 21 days of registration - ANC <1,000 cells/mm3, within 21 days of registration - Hemoglobin <8 g/dL, within 21 days of registration - Hepatic impairment (>/= 1.5 x institutional ULN or AST (SGOT), ALT (SGPT), or alkaline phosphatase >2 x ULN). Patients with benign hyperbilirubinemia are eligible. - Renal insufficiency (serum creatinine >2.5 mg/dl or creatinine clearance <60 ml/min, within 21 days of registration) - Respiratory compromise (DLCO < 50%) - Clinical signs of heart or coronary failure or LVEF < 40%. Myocardial infarction within 6 months prior to enrollment, NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conductive system abnormalities - Intercurrent illness including, but not limited to ongoing or active severe infection, known infection with hepatitis B or C virus, poorly controlled diabetes, severe uncontrolled psychiatric disorder or psychiatric illness/social situations that would limit compliance with study requirements - Previous history of another malignant condition except for basal cell carcinoma and stage I cervical cancer - Inability to comply with an anti-thrombotic treatment regimen - Peripheral neuropathy >/= Grade 2 Other exclusion criteria may apply. 7f4134ed46495ab3a000c5818439336d 8583 Vorinostat and Combination Chemotherapy With Rituximab in Treating Patients With Previously Untreated HIV-Related Diffuse Large B-Cell Non-Hodgkin Lymphoma I/II Ann Woolfrey, MD 2483.00 36; 48; 64 Hematologic Malignancies; Lymphoma; Non-Hodgkin's Lymphoma (NHL) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8583.html http://www.clinicaltrials.gov/ct/search?term=NCT01193842 NCT01193842 RATIONALE: Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and help kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Giving vorinostat together with combination chemotherapy and rituximab may kill more cancer cells. PURPOSE: This randomized phase I/II trial is studying the side effects and the best dose of vorinostat when given together with combination chemotherapy and rituximab to see how well it works compared to combination chemotherapy and alone in treating patients with previously untreated HIV-related diffuse large B-cell non-Hodgkin lymphoma. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both DISEASE CHARACTERISTICS: Histologically or cytologically confirmed diffuse large B-cell non-Hodgkin lymphoma - CD20-positive (CD20+) tumor as defined by the 2008 WHO classification - Patients with only a subset of tumor cells that are CD20+ allowed - Tumors should be tested for EBV expression by IHC or in situ hybridization Previously untreated disease All stages of disease allowed CD4 count = 50 cells/mm³ Must meet 1 of the following risk sets of criteria: - Low-risk - Age-adjusted (aa)-international prognostic index (IPI) scores: 0-1 factors* - Ki-67 < 80% - Germinal center B-cell-like (GCB) subtype (if known) - High-risk - aa-IPI: 2-3 factors* - Ki-67 = 80% - Activated B-cell-like (ABC, also known as post-GCB) subtype NOTE: * Adverse factors include stage III-IV disease, elevated serum LDH, or ECOG performance status of = 2. Serologically confirmed HIV infection by ELISA or western blot, or by another federally approved licensed HIV test - Prior documentation of HIV seropositivity allowed Measurable or non-measurable tumor - Non-measurable tumor parameters are defined as not having bidimensional measurements (e.g., gastric or marrow involvement), but that can be followed for response by other diagnostic tests such as gallium, PET imaging, and/or bone marrow biopsy No CNS involvement including parenchymal brain or spinal cord lymphoma, or known leptomeningeal disease PATIENT CHARACTERISTICS: See Disease Characteristics ECOG performance status (PS) 0-2 (Karnofsky PS 50-100%) Life expectancy = 2 months ANC = 1,000/mm³ Platelet count = 75,000/mm³ (unless abnormal due to lymphomatous involvement of bone marrow) Creatinine < 2.0 mg/dL OR creatinine clearance = 60 mL/min (< 50 mL/min if due to kidney involvement by tumor) Total bilirubin = 1.5 times upper limit of normal (ULN) (unless due to hepatic involvement or HIV medication such as indinavir, tenofovir, or atazanavir [drug adjustment may be needed fi direct bilirubin > 1.2 times ULN due to hepatic involvement]) AST and ALT = 2.5 times ULN (unless elevated due to secondary lymphomatous involvement of the liver) LVEF normal by MUGA scan or ECHO within the past 6 weeks Negative pregnancy test Not pregnant or nursing Fertile patients must use effective contraception during and for 6 months after completion of study treatment Able to swallow oral medications No second active malignancy except nonmelanoma skin cancer, carcinoma in situ of the cervix, or Kaposi sarcoma not requiring systemic therapy No active hepatitis B virus (HBV) (surface-antigen or core-antigen positive) - HBV core-antibody positive allowed provided patient starts or is on prophylactic therapy No known chronic hepatitis C virus infection Must be able to comply with protocol requirements and provide adequate informed consent, in the opinion of the principal investigator No serious, ongoing, non-malignant disease or infection, including opportunistic infections that, in the opinion of the investigator and/or the sponsor, would compromise other protocol objectives No history of cutaneous or mucocutaneous reactions, or other disease due to any cause, severe enough to cause hospitalization or inability to eat or drink for > 2 days No acute, inter-current infection that may interfere with planned protocol treatment - Patients with mycobacterium avium infection allowed None of the following: - Myocardial infarction within the past 6 months - NYHA class II-IV heart failure - Uncontrolled angina - Severe uncontrolled ventricular arrhythmias - Clinically significant pericardial disease - Electrocardiographic evidence of acute ischemic or active conduction system abnormalities PRIOR CONCURRENT THERAPY: See Disease Characteristics At least 24 hours since prior colony-stimulating factor therapy More than 4 weeks since prior major surgery other than diagnostic surgery No prior rituximab with the past 12 months - Prior rituximab within the past 12 months for indications other than treatment for aggressive lymphoma allowed No prior cytotoxic chemotherapy or radiotherapy for this lymphoma - Concurrent radiotherapy with or without steroids, or steroids alone, for emergency conditions secondary to lymphoma (e.g., cord compression) allowed No prior valproic acid or another histone deacetylase inhibitor within the past 2 weeks Concurrent highly active antiretroviral (HAART) regimen that is in accordance with the current International AIDS Society guidelines allowed - Changes to HAART therapy allowed if medically necessary (e.g., toxicity, failure of regimen) - HAART-naive patients must start therapy after completion of course 1 of chemotherapy - Concurrent agents currently available on expanded access program allowed - No experimental antiretroviral agents - No concurrent agents containing zidovudine, including Combivir® and Trizivir® - Zidovudine or a zidovudine-containing regimen (including Combivir® and Trizivir®) is prohibited until 2 months after completion of study chemotherapy Concurrent chronic therapy with potentially myelosuppressive agents allowed provided hematologic criteria are met Other eligibility criteria may apply. Other exclusion criteria may apply. 2cbe59730042f9671590e44a24ad2608 8595 Autologous Transplant in HIV Patients (BMT CTN 0803) II Ann Woolfrey, MD 2485.00 36; 38; 48 Hematologic Malignancies; Hodgkin's Lymphoma; Lymphoma Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8595.html http://www.clinicaltrials.gov/ct/search?term=NCT01141712 NCT01141712 This study is a Phase II, multicenter trial assessing overall survival after autologous hematopoietic stem cell transplantation using a BEAM transplant regimen in lymphoma patients with HIV. Ages Eligible for Study: 15 Years and older Genders Eligible for Study: Both - Diagnosis of persistent or recurrent WHO classification diffuse large B-cell lymphoma, composite lymphoma with > 50% diffuse large B-cell lymphoma, mediastinal B-cell lymphoma, immunoblastic, plasmablastic, Burkitt's or Burkitt-like or classical Hodgkin's lymphoma. Patients transformed from follicular lymphoma are eligible for the study, pending fulfillment of other criteria. - 15 years old or older - Three or fewer prior regimens of chemotherapy over the entire course of their disease treatment (including one induction chemotherapy and no more than 2 salvage chemotherapies). Monoclonal antibody therapy and involved field radiation therapy will not be counted as prior therapies. - All patients must have chemosensitive disease as demonstrated by at least a partial response to induction or salvage therapy. - Less than or equal to 10% bone marrow involvement. - Patients with adequate organ function as measured by: a) Cardiac: American Heart Association Class I: Patients with cardiac disease but without resulting limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea, or anginal pain. Additionally, all patients must have a left ventricular ejection fraction at rest greater than or equal to 40% demonstrated by MUGA or echocardiogram; b) Hepatic: (i) Bilirubin less than 2.0 mg/dL (except for isolated hyperbilirubinemia attributed to Gilbert syndrome or antiretroviral therapy) and ALT and AST greater than 3x the upper limit of normal; (ii) Concomitant Hepatitis: Patients with chronic hepatitis B or C may be enrolled on the trial providing the above criteria are met. In addition, no active viral replication - undetectable (viral load less than 500 copies/ml) hepatitis B DNA level by PCR and no clinical or pathologic evidence of irreversible chronic liver disease; c) Renal: Creatinine clearance (calculated creatinine clearance is permitted) greater than 40 mL/min; d) Pulmonary: DLCO, FEV1, FVC greater than or equal to 45% of predicted (corrected for hemoglobin). - Autologous peripheral stem cell graft with a minimum of greater than or less than 1.5 x 10^6 CD 34+ cells/kg (target greater than or less than 2.0 x 10^6 CD 34+ cells/kg) or if PBSC mobilization fails, cells can be obtained by bone marrow harvest per institutional practices (in cases where bone marrow will be used for transplantation, the required CD34+ dose does not apply and institutional requirements for total nucleated cell dose should apply). - Initiate conditioning therapy within 3 months of mobilization or bone marrow harvest. - Signed informed consent. - Patients on antiretroviral therapies (ARVs) can either have: a) Undetectable HIV viral load (VL less than 50 copies); b) If VL detectable at less than 2000 copies/mL must have review of previous antiretroviral regimens or previous genotypic or phenotypic testing which indicate the ability to fully suppress virus by addition of sensitive drugs. This review will be carried out by the ID specialist caring for the patient; c) If VL detectable at greater than 2000 copies/mL, a current HIV genotype and/or phenotype must be obtained. If a HAART regimen to which the patient's virus is sensitive can be determined based on genotype and previous antiretroviral experience, then the patient will be considered eligible in this regard. This review will be carried out by the ID specialist caring for the patient. Other eligibility criteria may apply. - Karnofsky performance score less than 70%. - Uncontrolled bacterial, viral or fungal infection (currently taking medication and with progression or no clinical improvement). - Prior malignancy in the 5 years prior to enrollment except resected basal cell carcinoma, treated cervical carcinoma in situ or Kaposi's sarcoma: a)Symptomatic Kaposi's sarcoma currently requiring therapy is excluded (patients receiving topical therapy for minimal disease are not included in this definition); b)Prior treatment with topical agents, local radiation, or up to 6 cycles of cytotoxic chemotherapy at least six months prior is permitted; c) Other cancers treated with curative intent less than 5 years previously will not be allowed unless approved by the Medical Monitor or Protocol Chair; d)Cancer treated with curative intent more than 5 years previously will be allowed. - Pregnant (positive ß-HCG) or breastfeeding. - Fertile men or women unwilling to use contraceptive techniques from the time of initiation of mobilization until six-months post-transplant. - Prior autologous or allogeneic HCT. - Patients with evidence of MDS/AML or abnormal cytogenetic analysis indicative of MDS on the pre-transplant bone marrow examination. Pathology report documentation need not be submitted. Other exclusion criteria may apply. 2f10e9726df29e5bdaf79eec6cbb5212 8639 Reduced Intensity Conditioning Versus Myeloablative Conditioning for Acute Myeloid Leukemia or Myelodysplastic Syndrome (BMT CTN 0901) III Bart Scott, MD 2497.00 2; 36; 43; 61 Acute Myeloid Leukemia (AML); Hematologic Malignancies; Leukemia; Myelodysplastic and Myeloproliferative Syndromes (MDS and MPD) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8639.html http://www.clinicaltrials.gov/ct/search?term=NCT01339910 NCT01339910 The study is designed as a Phase III, multicenter trial comparing outcomes after allogeneic hematopoietic stem cell transplantation (HCT) for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) between patients receiving myeloablative conditioning (MAC) versus reduced intensity conditioning (RIC) regimens. Ages Eligible for Study: 18 Years to 65 Years Genders Eligible for Study: Both Age equal or less than 65 years old and equal to or greater than 18 years old. - Patients with the diagnosis of MDS or AML with fewer than 5% myeloblasts in the bone marrow and no myeloblasts in the peripheral blood on morphologic analysis performed within 30 days of start of the conditioning regimen. Pre-transplant bone marrow sample must be evaluable for assessment of remission status (i.e. aspirate smear containing particles and/or evaluable bone marrow core biopsy). - For patients receiving treatment of their MDS or AML prior to transplantation: a)Interval between the start of a cycle of conventional cytotoxic chemotherapy and the start of conditioning regimen must be at least 30 days; b)Interval between completing treatment with a hypomethylating agent or other non-cytotoxic chemotherapy and the start of conditioning regimen must be at least 10 days. - HCT-Specific Comorbidity Index Score (HCT-CI) less than or equal to 4. - Organ function: a) Cardiac function: Symptomatic coronary artery disease or ejection fraction greater than or equal to 40%; b) Hepatic function: total bilirubin less than or equal to 2 times the upper limit of normal and ALT and AST less than or equal to 3 times the upper limit of normal.; c)Pulmonary function: DLCO greater than or equal to 40%, FEV1 greater than or equal to 50% (corrected for hemoglobin. - Creatinine clearance greater than or equal to 50mL/min/1.73m^2. - Signed informed consent. Other eligibility criteria may apply. - Circulating peripheral blood myeloblasts on morphologic analysis from time of last treatment to time of enrollment. - Prior allograft or prior autograft. - Active CNS disease as identified by positive CSF cytospin at time of enrollment. - Karnofsky Performance Score less than 70. - Patients receiving supplemental oxygen. - Planned use of DLI therapy. - Patients with uncontrolled bacterial, viral or fungal infections (undergoing appropriate treatment and with progression of clinical symptoms). - Patients seropositive for the human immunodeficiency virus (HIV). - Patients with prior malignancies, except resected basal cell carcinoma or treated cervical carcinoma in situ or other cancer treated with curative intent greater than 5 years previously. Cancer treated with curative intent less than 5 years previously will not be allowed unless approved by the Protocol Officer or one of the Protocol Chairs. - Females who are pregnant or breastfeeding. - Fertile men and women unwilling to use contraceptive techniques during and for 12 months following treatment. - Patients unable to communicate in English will be excluded from collection of patient-reported outcomes. Other exclusion criteria may apply. 0305a6e28bb72bc8f667707fe16136e9 8898 Laboratory-Treated T Cells in Treating Patients With High-Risk Relapsed Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Chronic Myelogenous Leukemia Previously Treated With Donor Stem Cell Transplant I/II Merav Bar, MD 2498.00 2; 11; 43 Acute Myeloid Leukemia (AML); Bone Marrow and Hematopoietic Stem Cell Transplant (BMT and HSCT); Leukemia Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8898.html http://www.clinicaltrials.gov/ct/search?term=NCT01640301 NCT01640301 This phase I/II trial studies the side effects of laboratory-treated T cells and to see how well they work in treating patients with high-risk relapsed acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or chronic myelogenous leukemia (CML) previously treated with donor stem cell transplant. Biological therapies, such as cellular adoptive immunotherapy, may stimulate the immune system in different ways and stop cancer cells from growing. Placing a gene that has been created in the laboratory into a person's T cells may make the body build an immune response to kill cancer cells Genders Eligible for Study: Both - Patients must express human leukocyte antigen (HLA)-A*0201 - Patients undergoing matched allogeneic hematopoietic cell transplantation (HCT) for: -- A) Acute Myeloid Leukemia (AML) including: ---- i) AML beyond first remission, therapy-related AML at any stage, primary refractory AML, AML in relapse (before or after HCT), AML with evidence of minimal residual disease (MRD) at time of HCT or after HCT (by multiparameter flow cytometry, cytogenetics, fluorescence in situ hybridization [FISH] or molecular studies); AML at any stage arising in a patient with an antecedent diagnosis of a hematologic disorder including myelodysplastic or myeloproliferative syndrome (e.g. chronic myelomonocytic leukemia, polycythemia vera, essential thrombocytosis, and agnogenic myeloid metaplasia with myelofibrosis) ---- ii) AML at any stage with unfavorable cytogenetic or molecular abnormalities: Monosomal karyotype (presence of two or more distinct autosomal chromosome monosomies or a single autosomal monosomy associated with at least one structural abnormality), del(5q)/-5, -7/del(7q), abn 3q, 9q, 11q, 20q, 21q, 17p, t(6;9), t(9;22), complex karyotype (>= 3 unrelated abnormalities), Inv(3) or t(3;3), t(6;11), +8 sole,+8 with 1 other abnormality other than t(8;21), t(9;11), inv (16), t(16;16), t(11;19), or normal cytogenetics with fms-related tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) mutation -- B) Myelodysplastic syndrome (MDS) including: ---- i) Intermediate-2 or high risk category patients according to the International Prognostic Scoring System (IPSS >= 1.5) or poor risk karyotype defined as abnormalities involving chromosome 7 or complex karyotype (>= 3 unrelated abnormalities) ---- ii) Relapsed disease post HCT -- C) Chronic Myeloid Leukemia (CML) including: ---- i) CML beyond chronic phase ---- ii) Relapsed disease post-HCT - Patients who previously underwent allogeneic HCT for AML, MDS or CML and have experienced overt relapse or minimal residual disease at any time post-HCT can be offered enrollment on the protocol and may undergo therapy on Arm 2 of the protocol - Patients must have an HLA-matched donor of hematopoietic stem cells (related or unrelated) - Patients must be able to provide blood and bone marrow samples and undergo the procedures required for this protocol - Patients must be >= 50 kg - Patients must be able to give informed consent; parent or legal representative will be asked to consent for patients younger than 18 year old - DONOR: Patient and donor (related or unrelated) must be HLA-matched and express HLA-A*0201 - DONOR: Donor must be Epstein-Barr virus (EBV) or cytomegalovirus (CMV) seropositive - DONOR: Donor must be age 18 or older - DONOR: In good general health - DONOR: Able to give informed consent Other eligibility criteria may apply. - Central nervous system (CNS) tumor refractory to intrathecal chemotherapy and/or cranio-spinal radiation - In patients whose leukemic cells are available for evaluation, expression of WT1 will be determined, and, if leukemic cells are negative for WT1 expression by polymerase chain reaction (PCR), the patient will be excluded from the study; patients with no evaluable leukemia will be eligible for enrollment based on the high frequency of positive leukemias (> 90%), and leukemia will be evaluated for WT1 expression if recurrence is detected - Human immunodeficiency virus (HIV) seropositive - Significant medical or psychological conditions that would make the patient unsuitable candidate for cell therapy at the discretion of the principal investigator (PI) - Pregnancy or breast-feeding; women of childbearing potential must have a negative serum or urine beta-human chorionic gonadotropin (hCG) pregnancy test result within 7 days before the first dose of WT1-specific T cell infusion; woman of non-childbearing potential will be defined as being postmenopausal greater than one year or who have had a bilateral tubal ligation or hysterectomy; all recipients of WT1-specific T cells will be counseled to use effective birth control during participation in this study and for 12 months after the last T cell infusion - DONOR: Less than 18 years old - DONOR: Active infectious hepatitis - DONOR: HIV or human T-lymphotropic virus (HTLV) seropositive - DONOR: Pregnancy or nursing - DONOR: Significant medical conditions (e.g. immunosuppressive therapy) that would make the donor unsuitable T cell donor - DONOR: Unable to give informed consent Other exclusion criteria may apply. 4dbd7c3acec450c108393bde4a98275f 8821 Bortezomib in Treating Patients With High-Risk Acute Myeloid Leukemia in Remission II John Pagel, MD, PhD 2529.00 2; 36; 43 Acute Myeloid Leukemia (AML); Hematologic Malignancies; Leukemia Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8821.html http://www.clinicaltrials.gov/ct/search?term=NCT01465386 NCT01465386 This phase II trial studies how well bortezomib works in treating patients with high-risk acute myeloid leukemia (AML) in remission. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. - Ages Eligible for Study: 18 Years and older - Genders Eligible for Study: Both - All adults with first remission AML including those with prior myelodysplasia (MDS)/AML, therapy-related AML, AML with trilineage dysplasia (AML-TLD), and AML with adverse cytogenetics - History of histopathologically documented AML that is currently in first remission with the presence of 5% or less blasts by morphology and/or flow cytometry from a bone marrow aspirate and/or biopsy obtained within 14 days of enrollment - Patients must start therapy between 3-8 weeks after receiving their last prior therapy (either induction therapy or consolidation therapy) - Patients may receive up to 4 courses of remission consolidation therapy (e.g., cytarabine) prior to enrollment - Normal kidney and liver function with serum creatinine =< 2.0 mg/dl - Total bilirubin =< 1.5 upper limit of normal (ULN) - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN - Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 - Male subjects, even if surgically sterilized (i.e., status postvasectomy) must agree to 1 of the following: practice effective barrier contraception during the entire study treatment period and through a minimum of 30 days after the last dose of study drug, or completely abstain from heterosexual intercourse - Female subject is either postmenopausal for at least 1 year before the screening visit, is surgically sterilized or if they are of childbearing potential, agree to practice 2 effective methods of contraception from the time of signing the informed consent form through 30 days after the last dose of bortezomib, or agree to completely abstain from heterosexual intercourse - Understand and voluntarily sign the informed consent form for this study Other eligibility criteria may apply. - Favorable AML features defined as the following: - 1) t(8;21)(q22;q22); RUNX1-RUNX1T1 - 2) inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11 - 3) Mutated NPM1 without FLT3-ITD (normal karyotype) - 4) Mutated CEBPA (normal karyotype) - Persistent clinically significant non-hematological toxicity that is > Grade 1 by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4 from prior chemotherapy - Active uncontrolled infection - Known infection with human immunodeficiency virus (HIV) - Medical condition, serious concurrent illness, or other extenuating circumstance that, in the judgment of the Principal Investigator, could jeopardize patient safety or interfere with the objectives of the study - Uncontrolled or significant cardiovascular disease, including: - 1) Uncontrolled angina or myocardial infarction within 6 months - 2) Current or history of congestive heart failure New York Heart Association (NYHA) class 3 or 4, unless a screening echocardiogram (ECHO) or Multiple Gate Acquisition Scan (MUGA) performed within 1 month prior to study screening results in a left ventricular ejection fraction (LVEF) that is >= 45% (or institutional lower limit of normal value) - 3) Prolonged QTc interval (> 450 msec) - Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy - Patient has a platelet count of < 30,000 within 3 days before enrollment - Patient has an absolute neutrophil count of < 300 within 3 days before enrollment - Patient has >= Grade 2 peripheral neuropathy - Patient has hypersensitivity to bortezomib, boron, or mannitol - Female patients who are lactating or have a positive urine pregnancy test during the screening; pregnancy testing is not required for postmenopausal or surgically sterilized women - Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and throughout the duration of this trial Other exclusion criteria may apply. 97269ba15858d270cd12b90ac20a78f7 8755 Scleroderma Treatment with Autologous Transplant (STAT) Study II George Georges, MD 2533.00 7; 85; 127 Autoimmune Diseases; Systemic Sclerosis; Non-malignant Condition Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8755.html http://www.clinicaltrials.gov/ct/search?term=NCT01413100 NCT01413100 This phase II trial studies how well giving cyclophosphamide and anti-thymocyte globulin together followed by peripheral blood stem cell transplant (PBSCT) and mycophenolate mofetil works in treating patients with systemic scleroderma (SSc). Stem cells are collected from the patient's blood and stored prior to treatment. To store the stem cells patients are given colony-stimulating factors, such as filgrastim (G-CSF) or chemotherapy (cyclophosphamide) to help stem cells move from the bone marrow to the blood so they can be collected and stored. After storage, patients are then given high-dose chemotherapy, cyclophosphamide, and immunosuppression with anti-thymocyte globulin to suppress the immune system to prepare for the transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy and immunosuppression. After the stem cells have "engrafted" and have matured enough to support the immune system at approximately 2-3 months, patients are given a medication called mycophenolate mofetil (MMF) or Myfortic. This medication is given to prevent worsening or reactivation of SSc and is referred to as maintenance therapy. Ages Eligible for Study: up to 69 Years Genders Eligible for Study: Both Group 1: - Patients must have 1) both a and b below; and 2) at least one of c, or d - a) Diffuse cutaneous scleroderma as defined by skin thickening proximal to the elbows and knees and/or involving the torso in addition to distal extremity involvement; a skin score will be obtained but not used to determine eligibility - b) Duration of systemic sclerosis =< 7 years from the onset of first non-Raynaud's symptom; for those patients with disease activity between 5-7 years from the onset of first non-Raynaud's symptom, recent progression or activity of disease must be documented - c) Presence of SSc-related pulmonary disease with forced vital capacity (FVC) < 80% or hemoglobin-adjusted diffusing capacity for carbon monoxide (DLCO) < 70% of predicted AND evidence of alveolitis by high-resolution chest computed tomography (CT) scan and/or by bronchoalveolar lavage (BAL) (if high resolution computed tomography [HRCT] fails to show ground glass, then BAL for diagnosis of alveolitis must be confirmed); alveolitis by BAL cell count will be defined based on a BAL cell differential count (> 3% neutrophils and/or > 2% eosinophils) from any lavaged lobe - d) History of SSc-related renal disease that may not be active at the time of screening; stable serum creatinine must be documented for a minimum of 3 months post-renal crisis at the time of the baseline visit; history of scleroderma hypertensive renal crisis is included in this criterion and is defined as follows: - History of new-onset hypertension based on any of the following (measurements must be repeated and confirmed at least 2 hours apart within 3 days of first event-associated observation, with a change from baseline): - Systolic blood pressure (SBP) >= 140 mmHg - Diastolic blood pressure (DBP) >= 90 mmHg - Rise in SBP >= 30 mmHg compared to baseline - Rise in DBP >= 20 mmHg compared to baseline - AND one of the following 5 laboratory criteria: - Increase of >= 50 % above baseline in serum creatinine - Proteinuria: >= 2+ by dipstick confirmed by protein:creatinine ratio > 2.5 - Hematuria: >= 2+ by dipstick or > 10 red blood cell (RBC)s/hematopoietic-promoting factor (HPF) (without menstruation) - Thrombocytopenia: < 100,000 platelets/mm^3 - Hemolysis: by blood smear or increased reticulocyte count - The above definition of SSc hypertensive renal crisis is independent of whether concomitant anti-hypertensive medications are used - Subjects who present with solely skin and renal disease in the absence of other organ involvement, except classic SSc renal crisis as described above and including non-hypertensive renal crisis, must see a nephrologist to confirm that their renal disease is secondary to only SSc - Note: Subjects may be re-screened if they fail to meet inclusion criteria on initial evaluation GROUP 2: - Progressive pulmonary disease as defined by a decrease in the FVC or DLCO-adjusted by 10 or 15 percent or greater, respectively, from a prior FVC or DLCO-adjusted in the previous 18-month period - Patients will have diffuse cutaneous disease and may have both FVC and DLCOcorr >= 70% at screening for the study - Patients must also have evidence of alveolitis as defined by abnormal chest computed tomography (CT) or bronchoalveolar lavage (BAL) GROUP 3: Diffuse scleroderma with disease duration =< 2 years since development of first sign of skin thickening plus modified Rodnan skin score >= 25 plus either - Erythrocyte sedimentation rate (ESR) > 25 mm/1st hour and/or hemoglobin (Hb) < 11 g/dL, not explained by causes other than active scleroderma - Lung involvement (either FVC or DLCO < 80% and evidence of interstitial lung disease by CT scan or alveolitis by BAL) GROUP 4: Diffuse scleroderma with disease duration =< 2 years and skin score >= 30 GROUP 5: - Limited cutaneous scleroderma and SSc-related pulmonary disease with FVC < 80% or hemoglobin-adjusted DLCO < 70% of predicted - AND evidence of alveolitis by high-resolution chest CT scan and/or by BAL (if HRCT fails to show ground glass, then BAL for diagnosis of alveolitis must be confirmed) - Alveolitis by BAL cell count will be defined based on a BAL cell differential count (> 3% neutrophils and/or > 2% eosinophils) from any lavaged lobe GROUP 6: Progressive gastrointestinal disease as defined by all of the following items: - Disease duration of scleroderma =< 2 years. - Documented severe malabsorption syndrome requiring nutritional support; severe malabsorption syndrome is > 10% weight loss and on total parenteral nutrition (TPN) or enteral feedings - High score on distention/ bloating scale (>= 1.60 out of 3.00) on gastrointestinal (GI) questionnaire Other eligibility criteria may apply. - Subjects with pulmonary, cardiac, hepatic, or renal impairment that would limit their ability to receive cytoreductive therapy and compromise their survival; this includes, but is not restricted to, subjects with any of the following: - Pulmonary dysfunction defined as: - Severe pulmonary dysfunction with (1) a hemoglobin corrected DLCO < 45% of predicted at the Clinical Review, (2) a hemoglobin-correct DLCO < 40% of predicted at the Baseline Screening visit, or (3) FVC < 45% of predicted at the Clinical review or Baseline Screening visit, or - Partial pressure (pO2) < 70 mmHg or pCO2 >= 45 mmHg without supplemental oxygen, or - O2 saturation < 92% at rest without supplemental oxygen as measured by forehead pulse oximeter - Significant pulmonary artery hypertension (PAH) defined as: - Peak systolic pulmonary artery pressure > 50 mmHg by resting echocardiogram will require right heart catheterization; if pulmonary artery pressure (PAP) is not evaluable on echocardiogram due to lack of a Tricuspid regurgitant jet, then normal anatomy and function as evidenced by normal right atrium and ventricle size, shape and wall thickness and septum shape must be documented to rule-out PAH; otherwise, right heart catheterization is indicated; prior history of PAH but controlled with medications will not exclude patients from the protocol; PAH is considered controlled with medications if peak systolic pulmonary artery pressure is < 45 mmHg or mean pulmonary artery pressure by right heart catheterization is < 30 mmHg at rest - Mean pulmonary artery pressure by right heart catheterization exceeding 30 mmHg at rest; if mean PAP is elevated and pulmonary vascular resistance and transpulmonary gradient are normal then the patient is eligible for the protocol - New York Heart Association (NYHA)/World Health Organization Class III or IV - Cardiac: Uncontrolled clinically significant arrhythmias; clinical evidence of significant congestive heart failure (CHF) (NYHA Class III or IV); left ventricular ejection fraction (LVEF) < 50% by echocardiogram or prior insertion of a pacemaker or cardioverter-defibrillator - History/presence of arrhythmia (even controlled) on chemical anti-arrhythmic(s) must have cardiac consult prior to randomization to ensure the subject could safely proceed with protocol requirements - Significant renal pathology defined as: - Estimated creatinine clearance (CrCl) < 40 mL/min (using Cockcroft-Gault formula based on actual body weight) and serum creatinine > 2.0 mg/dL; OR - Active, untreated SSc renal crisis at the time of enrollment; presence of nephrotic range proteinuria (defined as >= 3.5 gms/24 hours, or protein:creatinine ratio >= 3.5), active urinary sediment, urinary RBCs > 25 per HPF, or red cell casts require further investigation by a nephrologist to rule out glomerulonephritis, overlap syndromes, or other causes of renal disease in all subjects; subjects with glomerulonephritis or overlap syndromes will be excluded - Hepatic: Active hepatitis (alanine aminotransferase [ALT], aspartate aminotransferase [AST], or bilirubin > 2 times the upper limit of normal [ULN]) or evidence of moderate to severe periportal fibrosis by liver biopsy - Active or clinically significant Gastric Antral Vascular Ectasia (GAVE, "watermelon stomach") - Unwilling or unable to discontinue disallowed disease-modifying antirheumatic drugs (DMARDs) for treatment of SSc at time of randomization - History or presence of a 2nd autoimmune disease requiring immunosuppressive therapy that has substantial risk of immunosuppressive treatment beyond transplant with the following exceptions: - History and/or presence of Sjogren's Syndrome is allowed - Stable myositis (A history of myositis that is clinically stable as defined by lack of progressive proximal muscle weakness and a stable or decreasing creatine phosphokinase [CPK] < 3 x ULN) is allowed - The presence of anti-double stranded (ds)-deoxyribonucleic acid (DNA) without clinical systemic lupus erythematosus in a patient with a diagnosis of otherwise "pure" SSc is allowed - Concomitant rheumatoid arthritis without extra-articular disease characteristic of rheumatoid arthritis is allowed - Active uncontrolled infection that would be a contraindication to safe use of high-dose therapy - Positive study for Hepatitis B surface antigen or Hepatitis B or C confirmed by polymerase chain reaction (PCR) - Positive serology for human immunodeficiency virus (HIV) - Absolute neutrophil count (ANC) < 1500 cells/uL - Platelets < 100,000 cells/uL - Hematocrit < 27% - Hemoglobin < 9.0 g/dL - Malignancy within the 2 years prior to randomization, excluding adequately treated squamous cell skin cancer, basal cell carcinoma, and carcinoma in situ; treatment must have been completed (with the exception of hormonal therapy for breast cancer) with cure/remission status verified for at least 2 years at time of randomization - Presence of other comorbid illnesses with an estimated median life expectancy < 5 years - Evidence of myelodysplasia (MDS); subjects with history of receiving any prior chemotherapy and/or radiotherapy for the treatment of malignant disease, history of greater than 2 months total prior cyclophosphamide for any condition (regardless of dose and route) and/or subjects presenting with abnormal peripheral blood counts require unilateral bone marrow aspiration for pathology, flow cytometry, cytogenetics, and fluorescence in situ hybridization (FISH) MDS panel (per institutional profile) to rule out MDS - Pregnancy - Inability to give voluntary informed consent - Unwilling to use contraceptive methods for at least 15 months after starting treatment Other exclusion criteria may apply. 3600341afd26eba5ef165acd46a0478f 8888 Autologous T Cells, Low-Dose Recombinant Interferon Gamma, Cyclophosphamide, and Low-Dose Aldesleukin in Treating Patients With Soft Tissue Sarcoma That is Metastatic or Cannot Be Removed By Surgery I Seth Pollack 2537.00 77; 83 Sarcoma; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8888.html http://www.clinicaltrials.gov/ct/search?term=NCT01477021 NCT01477021 This phase I trial studies the side effects and how well giving autologous T cells together with cyclophosphamide works in treating patients with soft tissue sarcoma that is metastatic or cannot be removed by surgery. Biological therapies, such as cellular adoptive immunotherapy, may stimulate the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving autologous T cells together with cyclophosphamide may kill more tumor cells. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Histopathological documentation of the diagnosis of synovial sarcoma or myxoid liposarcoma with metastatic or unresectable disease who have received an alkylating agent containing regimen (such as doxorubicin plus Iphosphamide); this includes patients who received an alkylating agent as part of adjuvant therapy and then relapsed; patients who were treated on the PICCASSO trial who have progressed will be allowed on the study; "unresectable disease" shall include patients with locally advanced disease where a surgery could be attempted but where this surgery would be mutilating, debilitating and would likely fail to result in long-term disease free survival; in this setting a patient might reasonably choose to undergo salvage/second line systemic therapy but could also pursue aggressive surgical options as standard of care - Able to tolerate high-dose cyclophosphamide - NY-ESO-1 expression in > 25% of tumor by immunohistochemistry (IHC) (at least 2+) - Expression of human leukocyte antigen (HLA)-A0201; high resolution HLA typing performed at any experienced HLA lab will be accepted - Zubrod performance status of '0-1' - Patients with metastatic disease must have bi-dimensionally measurable disease by palpation on clinical exam, or radiographic imaging (computed tomography [CT] scan) - All patients must have an electrocardiogram (ECG); all patients must have a normal stress test within 182 days prior to treatment - Patients must have already been leukapheresed on either protocol 1246 or 2365 prior to entry into this study; patients who are unable to have a leukapheresis product collected, for whatever reason, will be unable to participate in this study - If there is a patient with an NY-ESO-1 expressing sarcoma who would be otherwise eligible for the trial, where there has been disagreement between pathologists regarding the histopathologic diagnosis, eligibility will be decided on by the principal investigator (PI) - Patients must have had NY-ESO-1 specific cells already in production; patients must have NY-ESO-1 specific cells that have been generated and sorted; these cells may be either in the process of expansion or expanded and frozen at the time of enrollment - Patients with definitively treated brain metastasis and patients with 4 or fewer untreated lesions less than 1 cm each will be included at the discretion of the principle investigator (PI) - Patients must be off metformin at least 2 weeks before receiving T cell therapy - Patients must have hemoglobin A1C < 8.5% Other eligibility criteria may apply. - Patients for whom we are unable to generate NY-ESO-1 specific cells - Pregnant women, nursing mothers, men or women of reproductive ability who are unwilling to use effective contraception or abstinence; women of childbearing potential must have a negative pregnancy test within two weeks prior to entry - Serum creatinine > 1.5 mg/dL or Glomerular Filtration Rate < 50 - Significant hepatic dysfunction (serum glutamic oxaloacetic transaminase [SGOT] > 150 IU or > 3x upper limit of normal [ULN]) - Bilirubin > 1.6 mg/dL - Prothrombin time (PT) > 1.5 x control - Most patients with metastatic sarcoma will have pulmonary metastasis and it is expected that the majority will have some mild to moderate baseline shortness of breath; these patients will be allowed on study so long as their Eastern Cooperative Oncology Group (ECOG) performance status is 1; patients with severe pulmonary dysfunction (>= Grade 3 Respiratory disorders as defined by Common Terminology Criteria for Adverse Events [CTCAE] v4) will not allowed on study until their condition improves; however, patients who have recently experienced a decrease in their pulmonary function will be required to undergo pulmonary function testing; patients with a forced expiratory volume in one second (FEV1) < 1.5L or diffusing capacity of carbon monoxide (DLco) (corr for hemoglobin [Hgb]) < 50% will be excluded; patients with a reversible cause of pulmonary dysfunction may undergo repeat testing and enroll if their pulmonary function tests (PFT's) meet criterion - All patients must have an echo showing ejection fraction (EF) > 50% and normal troponin and creatine kinase (CK) MB (echo may be done at the time of stress test as a stress echo); furthermore the following significant cardiovascular abnormalities will be excluded: --- Active, symptomatic congestive heart failure --- Clinically significant hypotension --- Symptoms of coronary artery disease --- Presence of cardiac arrhythmias on EKG requiring drug therapy which has not been stable for at least 6 months - Patients with symptomatic untreated brain metastasis or asymptomatic untreated brain metastasis > 1cm will not be allowed to participate; additionally, patients with five or more untreated brain metastasis under 1 cm will not be allowed to participate; treatment may include surgery or stereotactic radiation at the discretion of the patient's treatment team; patients must be off steroids when starting therapy - Patients with active infections or oral temperature > 38.2 C within 72 hours of study entry or systemic infection requiring chronic maintenance or suppressive therapy - Chemotherapeutic agents (standard or experimental or other immunosuppressive therapies) less than 3 weeks prior to T cell therapy; (patients with bulky disease may undergo cytoreductive chemotherapy but treatment will be discontinued at least 3 weeks prior to T cell infusion); patients may receive palliative radiation therapy two weeks prior to T cell infusion - Clinically significant autoimmune disorders or conditions of immunosuppression; patients with acquired immune deficiency syndrome (AIDS) or human immunodeficiency virus (HIV)-1 associated complex or known to be HIV antibody seropositive or known to be recently pathologic complete response (PCR)+ for hepatitis are not eligible for this study; virology testing will be done within 6 months of T cell infusion; the severely depressed immune system found in these infected patients and the possibility of premature death would compromise study objectives - Current treatment with steroids - Patients must not be receiving any other experimental drugs within 3 weeks of the initiation of treatment and must have recovered from all side effects of such therapy - Patients who were not negative for hepatitis B virus (HBV), hepatitis C virus (HCV) at the time of their leukapheresis on 1246 or 2365 must be retested to be sure they are PCR negative - Patients with a history of myocarditis, pericarditis, endocarditis Other exclusion criteria may apply. 8545c83f0407c6d4f7959aa59d7c6294 8794 Cyclophosphamide for Prevention of Graft-Versus-Host Disease After Allogeneic Peripheral Blood Stem Cell Transplantation in Patients With Hematological Malignancies II Marco Mielcarek, MD 2541.00 15; 38; 43; 48; 57; 61; 96 Burkitt's Lymphoma; Hodgkin's Lymphoma; Leukemia; Lymphoma; Multiple Myeloma (MM); Myelodysplastic and Myeloproliferative Syndromes (MDS and MPD); Chronic Graft Versus Host Disease (cGVHD) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8794.html http://www.clinicaltrials.gov/ct/search?term=NCT01427881 NCT01427881 This phase II trial studies how well cyclophosphamide works in preventing chronic graft-versus-host disease after allogeneic peripheral blood stem cell transplant in patients with hematological malignancies. Giving chemotherapy and total-body irradiation before transplantation helps stop the growth of cancer cells and prevents the patient's immune system from rejecting the donor's stem cells. Healthy stem cells from a donor that are infused into the patient help the patient's bone marrow make blood cells; red blood cells, white blood cells, and platelets. Sometimes, however, the transplanted donor cells can cause an immune response against the body's normal cells, which is called graft-versus-host disease (GVHD). Giving cyclophosphamide after transplant may prevent this from happening or may make chronic GVHD less severe. Ages Eligible for Study: up to 65 Years Genders Eligible for Study: Both - Acute lymphocytic leukemia (ALL) in morphologic first complete remission (CR1) with high risk features defined as, but not limited to: evidence of adverse cytogenetics such as t(9;22), t(1;19), t(4;11), or mixed-lineage leukemia (MLL) rearrangements; presence of minimal residual disease; progenitor B-cell immunophenotype; high white blood cells (WBC) at diagnosis (> 30,000/ul in B-ALL; > 100,000/ul in T-ALL); or delayed attainment of CR (> 4 weeks) after induction therapy; additional clinical characteristics deemed to confer a high relapse risk may be discussed with and approved by the Principal Investigator (PI) - Acute myeloid leukemia (AML) in CR1 EXCEPT patients with low-risk features defined as: - a) Inv 16 or t(8;21) in the absence of c-kit mutations - b) Normal karyotype who are FLT3-ITD-negative and NPM1-positive in the absence of c-kit mutations - c) Patients with respective "low-risk" features are eligible, however, if (i) more than 1 cycle of induction therapy was required to achieve CR1 (ii) the patient had a preceding myelodysplastic syndrome (MDS) other than myelofibrosis, or (iii) secondary AML - Acute leukemia in 2nd or greater CR (CR >= 2) - Refractory or relapsed AML with =< 10% bone marrow blasts and no circulating blasts or proven extramedullary disease - AML transformed from myelodysplastic syndrome (MDS) with < 10% bone marrow blasts - MDS with following high risk features: - 1) High risk cytogenetics (including, but not limited to: 7q--, inv[3], t[3q], del[3q] or complex karyotype) - 2) International Prognostic Scoring System (IPSS) intermediate (INT)-2 or greater - 3) Treatment-related MDS - 4) Any phase of MDS if patient is < 21 years of age - Chronic myelogenous leukemia (CML) beyond 1st chronic phase or resistant or intolerant to tyrosine kinase inhibitors (adults) or any phase (pediatric < 21 years) - Chronic myelomonocytic leukemia - Philadelphia-negative myeloproliferative disorder - Lymphoma: relapsed chemotherapy-sensitive (complete or partial response) Hodgkin or non-Hodgkin lymphoma - Multiple myeloma-stage III - The patient or legal representative must be able to understand and give written informed consent - DONORS: The donor must be a genotypically HLA-identical sibling, a phenotypically HLA-matched first-degree relative, or an unrelated donor who is molecularly matched with the patient at HLA-A, B, C, DRB1 - DONORS: Donors must meet the selection criteria for administration of G-CSF (filgrastim) and apheresis defined by the Foundation for the Accreditation of Cell Therapy (FACT) and will be screened per the American Association of Blood Banks (AABB) - DONORS: Donors must be capable of giving informed consent Other eligibility criteria may apply. - Prior autologous or allogeneic stem cell transplant - Performance status > 2 (Eastern Cooperative Oncology Group [ECOG]) - Uncontrolled infection; the protocol principal investigator (PI) will be final arbiter if there is uncertainty regarding whether a previous infection is under adequate control to allow enrollment in the study - Positive serology for human immunodeficiency virus (HIV)-1, 2 or human T cell lymphotropic virus (HTLV)-1, 2 - Left ventricular ejection fraction < 45% or shortening fraction < 25%; no uncontrolled arrhythmias or symptomatic cardiac disease - Symptomatic pulmonary disease; forced expiratory volume in one second (FEV1), forced vital capacity (FVC), diffusion capacity of the lung for carbon monoxide (DLCO) =< 50% of predicted (corrected for hemoglobin) - Calculated (Cockroft-Gault) serum creatinine clearance =< 60 mL/min; if the calculated CrCl is 50-60 mL/min, but a measured CrCl by 24 hour urine collection is > 60 mL/min, this measurement is acceptable - Total serum bilirubin more than twice upper normal limit - Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) more than 3-fold higher than laboratory upper normal limits - Female patient must have negative beta-human chorionic gonadotrophin (beta-HCG) pregnancy test (all women of child bearing-potential must have test performed) - DONORS: Potential donors who for psychological, physiological, or medical reasons cannot tolerate administration of G-CSF or apheresis - DONORS: Donors who are allergic to filgrastim or Escherichia (E.) coli-derived proteins - DONORS: Donor-related risks to recipients - DONORS: Positive anti-donor lymphocytotoxic crossmatch - DONORS: Donors who are positive for HIV Other exclusion criteria may apply. 3dd88d0633cf4efa193fb2426bb0c446 8829 Crohn's Allogeneic Transplant Study (CATS) II George McDonald, MD 2551.00 11 Bone Marrow and Hematopoietic Stem Cell Transplant (BMT and HSCT) Crohn's Allogeneic Transplant Study Line 206/667-2287 http://studies.fhcrc.org/cats/ http://www.fhcrc.org/en/treatment/clinical-trials/detail.8829.html http://www.clinicaltrials.gov/ct/search?term=NCT01570348 NCT01570348 This phase II trial studies how well giving a donor bone marrow transplant (BMT) works in treating patients with refractory Crohn's Disease. We will select patients with severe Crohn's Disease and active inflammation despite the best medical and surgical treatments. These patients must be healthy enough to undergo a transplantation procedure. They cannot have an active infection, and their heart, lungs, kidneys, and liver cannot be failing. The transplant procedure starts with chemotherapy and a small dose of radiation, to weaken a patient's immune system so that it will accept bone marrow cells from another person. After that other person's bone marrow cells are given to the patient, immune suppressive medicines are given to prevent the new cells from being rejected and to stop those cells from damaging the patient. After the new donor cells start to work, blood counts will rise and the new immune system will start to grow. During this time, there is a risk of infection. Antibiotics and anti-viral drugs will be given to prevent infection. When the new donor cells are well-established, immune suppressive medicines are discontinued. We will examine parts of the intestine that were inflamed before the start of the transplant procedure, to be sure the Crohn's Disease has disappeared after the transplant. Patients will be formally evaluated for Crohn's activity at around 100 days after transplant, and yearly after that for 5 years. Ages Eligible for Study: 18 Years to 60 Years Genders Eligible for Study: Both - The patients that will be eligible for enrollment on this study are individuals with severe, treatment-refractory Crohn's Disease. - A diagnosis of CD established by referring physician(s) and confirmed by our review of the clinical presentation, clinical course, endoscopic and imaging findings, and histology of mucosal tissue specimens. - An adverse prognosis, documented by persistent signs and symptoms of CD that have failed to respond satisfactorily to medical and surgical therapies in the past, including but not limited to systemic immune suppressive drugs and biopharmaceuticals; patients should have relapsing inflammatory mucosal disease despite medications or clear demonstration of intolerance / toxicity to these drugs and biopharmaceuticals; to be considered as refractory to medical and surgical therapy, there must be clinical, endoscopic, and histologic evidence of active inflammatory Crohn's Disease that has either persisted or recurred despite exhaustive treatment with available pharmaceutical and surgical therapies; exhaustive treatment is defined as prior exposure to the following, without durable improvement: -- a) Systemic glucocorticoids. -- b) Methotrexate and/or a thiopurine antimetabolite. If a patient is homozygous mutant for the TPMT gene, thiopurines would be contraindicated and their use would not be a requirement for enrollment in this protocol. -- c) Use of at least two anti-TNF-alpha therapies (infliximab and/or adalimumab and/or certolizumab pegol). -- d) Exhaustive surgical treatment will be defined as indicated operations for complications of Crohn's Disease up to the point where the risks of surgery are deemed by patients and their physicians to be unacceptably high. Indicated operations for complications of Crohn's Disease include, but are not limited to, surgical resection of involved intestine, stricturoplasty, drainage, curettage, or adhesiolysis of tissues affected by Crohn's disease. -- e) Exposure of patients to investigational drug therapies for Crohn's Disease, that is, to drugs that are not FDA approved for this indication, will not be a criterion for either inclusion or exclusion. -- In the event that the involved mucosa cannot be readily reached by endoscopic biopsy, an imaging test that shows typical changes of CD in the intestinal tract will suffice as evidence of active intestinal inflammation; the presence of intestinal stomas does not exclude the patient from study. - Severe CD as defined by one of the following: -- a) CDAI >= 250 -- b) Need for total parenteral nutrition to maintain weight -- c) Recurrent intestinal inflammation caused by CD following surgical resection - Identification of an HLA-matched hematopoietic cell donor without a history of a disorder that can be transmitted by hematopoietic cells, including but not limited to inflammatory bowel disease. - Age from 18 through 60 years. - DONORS will be an HLA-identical sibling or HLA-matched unrelated donor. Unrelated donors are required to be matched by high resolution allele level typing for HLA-A, B, C and DRB1 and intermediate resolution Sequence Specific Oligonucleotide Probes (SSOP), identifying alleles in groups of related families historically defined as antigens for DQB1. An unrelated donor is considered matched if patient and donor share HLA-A, B, C alleles with identical sequences at exons 2 and 3, DRB1 alleles with identical sequences at exon 2, and DQB1 results that include the same allele groups. - DONORS will have the ability to understand and the willingness to sign a written informed consent document for bone marrow harvest. Other eligibility criteria may apply. - Diagnosis of CD in a patient with an underlying immune deficiency disorder, including but not limited to severe combined immunodeficiency (SCID), immunodysregulation polyendocrinopathy enteropathy X-linked syndrome (IPEX), and others - A current complication of CD that would jeopardize survival after hematopoietic cell transplantation, including but not limited to the following: - a) Abscess, phlegmon, necrotizing skin lesion, or inflammatory fistula - b) Intestinal fibrotic stricture and intestinal obstruction - c) Uncontrolled mucosal, organ, or systemic infection with a bacterial, viral, fungal, or parasitic organism - d) Sclerosing cholangitis - History of progressive multifocal leukoencephalopathy - Organ dysfunction or disease that would jeopardize survival after hematopoietic cell transplantation, including but not limited to the following: - a) Renal insufficiency as defined by an estimated Glomerular Filtration Rate (GFR) < 60 mL/minute - b) Cardiac dysfunction as defined by symptomatic coronary artery disease, congestive heart failure, valvular heart disease, cardiomyopathy, uncontrolled arrhythmia(s), or left ventricular ejection fraction < 50% - c) Pulmonary dysfunction that poses a risk of mortality after transplant - d) Necroinflammatory or fibrotic liver disease with evidence of liver dysfunction, including but not limited to jaundice, hepatic encephalopathy, or portal hypertension - e) Marrow dysfunction that poses a risk of peri-transplant mortality - f) Poorly controlled hypertension despite appropriate therapy - g) Neurologic dysfunction that affects activities of daily living and medical care - h) Poorly controlled diabetes mellitus - I) Extreme protein-calorie malnutrition defined by Body Mass Index < 18 kg/m^2 and unintentional weight loss (3 kg in the last month or 6 kg in the last 6 months - Pregnancy - Fertile men or women unwilling to use contraceptive techniques during and for 12 months following transplant - History of smoking either tobacco or other herbal products in the last 6 months - Human immunodeficiency virus (HIV), hepatitis C virus, or hepatitis B virus seropositivity - Patients whose life expectancy is severely limited by illness other than CD - Untreated psychiatric illness, including drug/alcohol abuse, that would compromise compliance - Inability to give voluntary informed consent or obtain a parent or guardian's informed consent - Demonstrated lack of compliance with prior medical care - History of a malignancy, excluding adequately treated squamous cell skin cancer, basal cell carcinoma, and carcinoma in situ - Hematopoietic cell transplant-co-morbidity Index greater than 2 for adult patients - DONOR: Identical twin - DONOR: Pregnant or lactating females - DONOR: HIV seropositivity or presence of HBV DNA or HCV RNA in the serum - DONOR: Current serious systemic illness including uncontrolled infections - DONOR: Malignancy within 10 years prior to donation of marrow, excluding adequately treated squamous cell skin cancer and basal cell carcinoma; treatment must have been completed (with the exception of hormonal therapy for breast cancer) with cure/remission status verified for at least 10 years at time of marrow harvest - DONOR: History of or symptoms consistent with inflammatory bowel disease or a serious autoimmune disorder - DONOR: History of a serious disease or disorder that could be adoptively transferred by infusion of donor hematopoietic cells - DONOR: Failure to meet institutional criteria for donation as described in the Standard Practice Guidelines Other exclusion criteria may apply. 3a1821ca7cc3ad5f6db2f2982a3a4788 9038 Tosedostat in Combination With Cytarabine or Decitabine in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome II John Pagel, MD, PhD 2566.00 2; 43; 61 Acute Myeloid Leukemia (AML); Leukemia; Myelodysplastic and Myeloproliferative Syndromes (MDS and MPD) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9038.html http://www.clinicaltrials.gov/ct/search?term=NCT01567059 NCT01567059 This study examines a new oral chemotherapy drug called tosedostat, in combination with cytarabine or decitabine. Tosedostat is thought to work by decreasing the availability of amino acids (building blocks the cell needs to make proteins) in cells. It has been shown in early studies to have activity against a variety of cancers, including leukemias. Patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) with specific genetic mutations have a poorer response to chemotherapy and a higher risk of relapse after treatment. Researchers are looking to see if combinations of chemotherapy drugs may improve outcomes for patients that do not respond as well with the current chemotherapy regimens, without increasing the risks of treatment Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent - All adults >= 60 years of age with untreated AML or high-risk MDS (10-19% marrow blasts) including those with prior myelodysplasia (MDS)/AML, therapy-related AML, AML with trilineage dysplasia (AML-TLD), and AML with adverse cytogenetics; patients may be enrolled if they received prior treatment with hydroxyurea to control blood counts or demethylating agents specifically for the purpose of treating MDS - Adults age 18 to 59 with untreated AML or high-risk MDS and a transplant-related mortality (TRM) score of >= 9.2; previous data suggests these people would have a 25% mortality with standard therapy, making this treatment a reasonable alternative - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 - 2 - Serum creatinine =< 2.0 mg/dL; if serum creatinine > 2.0 mg/dL, then the estimated glomerular filtration rate (GFR) must be > 50 mL/min/1.73 m^2 as calculated by the Modification of Diet in Renal Disease equation - Serum bilirubin =< 1.5 × upper limit of normal (ULN) (in the absence of Gilbert's syndrome) - Aspartate transaminase (AST)/alanine transaminase (ALT) =< 2.5 × ULN - Alkaline phosphatase =< 2.5 × ULN - Male subjects, even if surgically sterilized (i.e., status postvasectomy) must agree to 1 of the following: practice effective barrier contraception during the entire study treatment period and through a minimum of 30 days after the last dose of study drug, or completely abstain from heterosexual intercourse - Female subject is either postmenopausal for at least 1 year before the screening visit, is surgically sterilized or if they are of childbearing potential, agree to practice 2 effective methods of contraception from the time of signing the informed consent form through 30 days after the last dose of study drug, or agree to completely abstain from heterosexual intercourse Other eligibility criteria may apply. - Favorable AML features defined as the following: t(8;21)(q22;q22); RUNX1-RUNX1T1 inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11 Mutated nucleophosmin (NPM)1 without fms-like tyrosine kinase receptor-3 (FLT3)- internal tandem duplication (ITD) (normal karyotype) Mutated CCAAT/Enhancer Binding Protein Alpha (CEBPA) (normal karyotype) - Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol - Active uncontrolled infection - Known infection with human immunodeficiency virus (HIV) - Medical condition, serious concurrent illness, or other extenuating circumstance that, in the judgment of the Principal Investigator, could jeopardize patient safety or interfere with the objectives of the study - Uncontrolled angina or myocardial infarction within 6 months - Current or history of congestive heart failure New York Heart Association (NYHA) class 3 or 4, unless a screening echocardiogram (ECHO) or multiple gate acquisition scan (MUGA) performed within 1 month prior to study screening results in a left ventricular ejection fraction (LVEF) that is >= 45% (or institutional lower limit of normal value) - Diagnosed or treated for another malignancy within 1 year of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy Other exclusion criteria may apply. 7971ad232851054027d0b96973e98baf 9352 Laboratory-Treated Donor Cord Blood Cell Infusion Following Combination Chemotherapy in Treating Younger Patients With Relapsed or Refractory Acute Myeloid Leukemia Pilot Colleen Delaney, MD, MSc 2584.00 2; 36; 43 Acute Myeloid Leukemia (AML); Hematologic Malignancies; Leukemia Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9352.html http://www.clinicaltrials.gov/ct/search?term=NCT01701323 NCT01701323 This pilot clinical trial studies infusion of laboratory-grown donor cord blood cells following combination chemotherapy in treating younger patients with relapsed or refractory acute myeloid leukemia. Chemotherapy drugs work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Chemotherapy also kills healthy infection-fighting cells, increasing the risk of infection. The infusion of laboratory-grown cord blood cells may be able to replace blood-forming cells that were destroyed by chemotherapy. This may decrease the risk of infection following chemotherapy, and allow for more chemotherapy to be given so that more cancer cells are killed. Ages Eligible for Study: 2 Years to 30 Years Genders Eligible for Study: Both - Patients must have a diagnosis of AML according to World Health Organization (WHO) classification with >= 5% of disease in bone marrow (BM), with or without extramedullary disease or biopsy-proven isolated myeloid sarcoma (myeloblastoma, chloroma, including leukemia cutis) in the absence of marrow involvement - AML: -- If relapse AML: ---- i) Must have a prior diagnosis of AML and be in 1st or greater relapse ---- ii) Must not have received prior reinduction therapy for this relapse -- If primary refractory AML: ---- i) Must have had a prior diagnosis of AML and ---- ii) Must not have received more than 3 previous induction attempts - Patients must be classified as central nervous system (CNS)1 or CNS 2 and without clinical signs of CNS leukemia such as cranial nerve palsy; patients with CNS 3 disease are not eligible - Must have a Lansky or Karnofsky performance status of >= 50; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age - Patients must have recovered from the acute toxicity of all prior chemotherapy; patients may not have received cytotoxic chemotherapy within 2 weeks of first dose of G-CSF (filgrastim) therapy, with exception of hydroxyurea, which is allowed for up to 24 hours prior to first dose of G-CSF, and intrathecal chemotherapy, which is allowed prior to, or in the 1st 72 hours after start of G-CSF therapy - The following amounts of time must have elapsed prior to entry on study: --- 2 weeks from local radiation therapy (XRT) --- 8 weeks from prior craniospinal or if > 50% of the pelvis has been irradiated --- 6 weeks must have elapsed if other bone marrow radiation has occurred - Creatinine within normal range for age (per institutional defined lab value ranges) - Direct bilirubin =< 1.5 upper limit of normal (ULN) age unless elevation thought to be due or hepatic infiltration by the hematologic malignancy - Alanine aminotransferase (ALT) < 5 x ULN age - Adequate cardiac function as defined as shortening fraction of > 27% OR ejection fraction of > 50% - Patients must have a calculated QT (QTc) interval < 450 ms on baseline echocardiogram - Patients must demonstrate a respiratory rate that is within normal limits for age, measured when afebrile and at rest (measured for a full minute) and pulse oximetry > 93% on room air - Signed informed consent - Patient must have a life expectancy of at least 2 months - Females of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment - Females of childbearing potential and males should agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation Other eligibility criteria may apply. - Recipient of prior allogeneic hematopoietic stem cell transplant (HCT) - Patients with history of Down's syndrome, Fanconi anemia or other known marrow failure condition - Patients with central nervous system (CNS) 3 disease or symptomatic CNS2 disease are not eligible - Patients currently receiving other investigational drugs are not eligible - Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol with the exception of intrathecal chemotherapy; this includes the tyrosine kinase inhibitor sorafenib which must not be initiated until patient demonstrates count recovery - Patients with a systemic fungal, bacterial, viral, or other infection not controlled despite appropriate antibiotics or other treatment; uncontrolled systemic infections require infectious disease consultation for verification - Patients who are platelet refractory prior to initiation of protocol therapy; platelet refractoriness is defined by platelet count < 50K when platelet count is obtained 1 hour post platelet transfusion - Pregnant or lactating patients - Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results Other exclusion criteria may apply. 91f07f6cf02380cd1126f9cf4e7a31a3 9398 Viral Oncoprotein Targeted Autologous T Cell Therapy for Merkel Cell Carcinoma I Aude Chapuis, MD 2586.00 81; 83 Skin Cancer; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9398.html http://www.clinicaltrials.gov/ct/search?term=NCT01758458 NCT01758458 This phase I/II trial studies the side effects and best way to give laboratory treated autologous T cells together with aldesleukin and to see how well it works in treating patients with metastatic Merkel Cell Carcinoma. Biological therapies, such as cellular adoptive immunotherapy, may stimulate the immune system in different ways and stop cancer cells from growing. Aldesleukin may stimulate the white blood cells to kill cancer cells. Giving cellular adoptive immunotherapy with aldesleukin may be a more effective treatment for metastatic Merkel cell carcinoma Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Histopathological documentation of MCC concurrent with the diagnosis of metastatic disease - Evidence of MCPyV TAg tumor expression - Available peptide-MHC pair that can be folded into a tetramer for which MCPyV TAg-specific cells can be generated and reactivity to cell lines expressing MCPyV TAg with the corresponding human leukocyte antigen (HLA) - Bi-dimensionally measurable disease by palpation, clinical exam, or radiographic imaging (x-ray, computed tomography [CT] scan, positron emission tomography [PET] scan, magnetic resonance imaging [MRI], or ultrasound) - At least 3 weeks must have passed since any of the following: systemic corticosteroids, immunotherapy (for example, interleukins, MCC vaccines, intravenous immunoglobulin, expanded polyclonal tumor infiltrating lymphocyte [TIL] or lymphokine-activated killer [LAK] therapy), pentoxifylline, other small molecule or chemotherapy cancer treatment, other investigational agents or other agents that target Merkel cell carcinoma Other eligibility criteria may apply. - Unable to generate antigen-specific MCPyV TAg-specific CD8+ T cells for infusions - Active infections or oral temperature > 38.2 Celsius (C) fewer than 72 hours prior to receiving study treatment or systemic infection requiring chronic maintenance or suppressive therapy - Eastern Cooperative Oncology Group (ECOG) performance status > 2 - White blood cell (WBC) < 2000/mcl - Hemoglobin (Hb) < 8 g/dL - Absolute neutrophil count (ANC) < 1000/mcl - Platelets < 50,000/mcl - New York Heart Association functional class III-IV heart failure, symptomatic pericardial effusion, stable or unstable angina, symptoms of coronary artery disease, congestive heart failure, clinically significant hypotension, or an ejection fraction of =< 30 % (echocardiogram or multi gated acquisition scan [MUGA]) - Clinically significant pulmonary dysfunction, as determined by medical history and physical exam; patients so identified will undergo pulmonary functions testing and those with forced expiratory volume in one second (FEV1) < 2.0 L or diffusing capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin [Hgb]) < 50% will be excluded - Creatinine clearance < 30 ml/min which cannot be attributed to MCC metastasis - Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 5 x upper limit of normal (ULN) - Bilirubin > 3 x ULN which cannot be attributed to MCC metastasis - Active autoimmune disease (e.g. systemic lupus erythematosus, vasculitis, infiltrating lung disease, inflammatory bowel disease) whose possible progression during treatment would be considered unacceptable by the investigators - Symptomatic and untreated central nervous system (CNS) metastasis; however, patients with 1-2 asymptomatic, less than 1 cm brain/CNS metastases without significant edema may be considered for treatment; if sub-centimeter CNS lesions are noted at study entry, then a repeat imaging will be performed if more than 4 weeks have elapsed from the last scan - Any condition or organ toxicity that is deemed by the principal investigator (PI) or the attending physician to place the patient at unacceptable risk for treatment on the protocol - Pregnant women, nursing mothers, men or women of reproductive ability who are unwilling to use effective contraception or abstinence; women of childbearing potential must have a negative pregnancy test within two weeks prior to entry - Clinically significant and ongoing immune suppression including, but not limited to, systemic immunosuppressive agents such as cyclosporine or corticosteroids, chronic lymphocytic leukemia (CLL), uncontrolled human immunodeficiency virus (HIV) infection, or solid organ transplantation _ Patients may not be on any other treatments for their cancer aside from those included in the protocol. Patients may not undergo another form of treatment concurrently with this study. Other exclusion criteria may apply. c0abacd10b02c0c3ee410f42932af9d6 9074 Decitabine Followed by Idarubicin and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndromes II Derek Stirewalt, MD 2588.00 2; 19; 43; 61 Acute Myeloid Leukemia (AML); Chronic Myeloid Leukemia (CML); Leukemia; Myelodysplastic and Myeloproliferative Syndromes (MDS and MPD) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9074.html http://www.clinicaltrials.gov/ct/search?term=NCT01607645 NCT01607645 The goals of this study are to learn about the effectiveness, the side-effects, if waiting to give the idarubicin and cytarabine may change the side effects or effectiveness, and to identify factors to predict for responses to this therapy. The trial will examine combination of three chemotherapy drugs. These drugs are decitabine, idarubicin, and cytarabine. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Written informed consent - All patients except those with acute promyelocytic leukemia (APL) who have morphological diagnosis of myelodysplastic syndromes (MDS) refractory anemia with excess blasts (RAEB)-II or AML by World Health Organization (WHO) diagnostic criteria and have either refractory or early relapsed disease; NOTE: --- Diagnosis of refractory or relapsed disease must be based on evaluation of a bone marrow (BM) aspirate or peripheral blood (PB) flow cytometry; other standard MDS and AML prognostic studies such as cytogenetics, flow, and molecular testing are highly recommended prior to initiating DAC --- A previous BM evaluation or PB flow cytometry from an outside facility are acceptable if the results have been deemed to be adequate for confirming the diagnosis and staging by University of Washington (UW)/Seattle Cancer Care Alliance (SSCA)/Fred Hutchinson Cancer Research Center (FHCRC) review --- A BM biopsy is not routinely required but should be obtained if the previous evaluation is not deemed to be adequate for confirming diagnosis and staging by UW/SCCA/FHCRC review - Must have received at least one previous cycle of treatment for MDS or AML and be either refractory as defined as not responded to this therapy or in early relapse as defined as developing recurrence of the disease within 12 months of obtaining a CR - May have previously received demethylating agents (e.g., DAC, 5-azacytidine [5AZA]) or histone deacetylases (e.g., suberoylanilide hydroxamic acid) for their MDS or AML if these demethylating agents were not used in combination with systemic anthracycline and ARAC chemotherapy - May have received hematopoietic growth factors, thalidomide/lenalidomide, signal transduction inhibitors, or low dose cytarabine (=< 20 mg/m2/day) - May not have received any therapy for their MDS or AML other than hydroxyurea or leukapheresis for at least 14 days prior to start of the first dose of DAC; all non-hematologic toxicities must have resolved to < grade 2 - Must have a "simplified" treatment-related mortality (TRM) score =< 9.2 - Females of childbearing potential must have a negative pregnancy test prior to initiation of the protocol therapy; females are considered not of child bearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal - Females of childbearing potential and males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 12 weeks after treatment discontinuation - Patients with an active or history of other malignancies are eligible, if their projected overall survival for that malignancy is at least 6 months - Prior hormonal therapy such as aromatase inhibitors, selective estrogen receptor modulators, estrogen receptor down-regulators, luteinizing hormone-releasing hormone (LHRH) agonists and antagonists, and anti-androgens, must be completed at least 30 days prior to initiation of protocol therapy and must remain off hormonal therapy until the patient has finished chemotherapy for their MDS-RAEBII or AML - Direct bilirubin =< 2.5 mg/dL (assessed within 14 days prior to registration) unless elevation is thought to be due to hepatic infiltration by AML, Gilbert's syndrome, or hemolysis - No known hypersensitivity to DAC, ARAC, or IDA - No clinical evidence of central nervous system (CNS) involvement with leukemia, unless a lumbar puncture confirms the absence of leukemic blasts in the cerebrospinal fluid (CSF) - No prior positive test for the human immunodeficiency virus (HIV) - No uncontrolled systemic infection Other eligibility criteria may apply. - Previous therapy with demethylating agents (e.g., DAC, 5AZA, etc.) or histone deacetylases (e.g., suberoylanilide hydroxamic acid, etc.) that was combined with daunorubicin (DNR) or IDA and ARAC - Patients with APL - Known hypersensitivity to DAC, ARAC, or IDA - Clinical evidence of CNS involvement with leukemia, unless a lumbar puncture confirms the absence of leukemic blasts in the CSF - Prior positive test for HIV - Uncontrolled systemic fungal, bacterial, viral, or other infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment) - A "simplified" TRM score > 9.2 - Bilirubin > 2.5 mg/dl (assessed within 14 days prior to registration), unless elevation is thought to be due to hepatic infiltration by AML, Gilbert's syndrome, or hemolysis - Patients who have a projected overall survival < 6 months due to malignancies other than MDS or AML - Documented symptomatic congestive heart failure or a documented left ventricular ejection fraction < 40% assessed by multi gated acquisition (MUGA), echocardiography, or heart catheterization within 21 days prior to start of decitabine Other exclusion criteria may apply. f5c9dda512a069ab188ef32f4afc9a27 9048 Hematopoietic Stem Cell Transplantation for the Treatment of Patients With Fanconi Anemia Lacking a Genotypically Identical Donor, Using a Chemotherapy Only Cytoreduction With Busulfan, Cyclophosphamide and Fludarabine II K.Scott Baker 2598.00 26; 36 Fanconi Anemia; Hematologic Malignancies Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9048.html http://www.clinicaltrials.gov/ct/search?term=NCT00987480 NCT00987480 This is a genetic disease (transmitted through the parents' genes) called Fanconi Anemia. Because of that genetic disease, the bone marrow has changed and now has failed, or has given rise to a preleukemia called myelodysplastic syndrome (MDS) or leukemia (acute myelogenous leukemia or AML). Without treatment these complications of Fanconia anemia (FA) are fatal. The only treatment that can cure these complications is an allogeneic transplant of stem cells, meaning, giving the patient bone marrow cells from a healthy donor that can produce normal blood cells that will replace the bone marrow that is sick. What has been given for the treatment of FA in the past is to use a combination of low doses of radiation to the whole body (total body irradiation) and low doses of the chemotherapy drugs (cyclophosphamide and fludarabine) before the transplant. However, the use of radiation can, later on, increase the chances of getting a second cancer of the skin, head or the neck. These chances of a second cancer are higher than normal in patients with FA. The purpose of this study is to find out if the doctors can do the same thing with the same chemotherapy drugs used in the past. However physicians will use another chemotherapy drug called busulfan instead of the radiation. The goal of this study is to get rid of the short term and long term risks of the radiation. The first new part of this treatment will be to replace drugs for radiation with chemotherapy drugs. Genders Eligible for Study: Both Accepts Healthy Volunteers: Yes - Patients must have a diagnosis of Fanconi anemia (confirmed by mitomycin C or diepoxybutane [DEB] chromosomal breakage testing at an approved laboratory). - Hematologic Diagnosis and Status - Patients must have one of the following hematologic diagnoses: --- Isolated Single lineage Cytopenia AND at least one of the following features: - Platelet count <20 x 109/L or platelet transfusion dependence* - ANC <1000 x 109/L - Hgb <8 gm/dl or red cell transfusion dependence* - Myelodysplastic Syndrome (MDS) (Appendix 1: MDS Classification) - MDS at any stage, based on either one of the following classifications: --- WHO Classification --- Refractory anemia and transfusion dependence* --- Any of other stages --- IPSS Classification --- Low risk (score 0) and transfusion dependence* --- Any other risk groups Score > or = to 0.5 - Acute Myelogenous Leukemia --- Patients with acute leukemia are included in this trial in remission, refractory or relapsed disease. --- Transfusion dependence will be defined as greater than ONE transfusion of platelets or red blood cells in the last year prior to evaluation on protocol. ***Donors: - Donor choices will be determined by the investigators at each of the centers according to their own institutional criteria. - All patients evaluated at trial sites and eligible for this trial by virtue of disease and lack of an HLA-genotypically matched related donor will be captured in the database of this trial. Patients who will be enrolled on this protocol must have one of the following donor choices: --- HLA-compatible Unrelated volunteer donors --- Patients who do not have a related HLA-matched donor but have an unrelated donor who is either matched at all A, B, C and DRB1 (8/8) loci or who is mismatched at 1/8 loci (A, B, C or DRB1) (7/8) as tested by DNA analysis (high resolution), will be eligible for entry on this protocol. --- HLA-mismatched Related donors --- Patients who do not have a related or unrelated HLA-compatible donor must have a healthy family member who is at least HLA-haplotype identical to the recipient. First degree related donors must have a normal DEB test. --- The donor must be healthy and willing and able to receive a 4-6 day course of G-CSF and undergo 1-3 daily leukaphereses. --- Related and Unrelated donors must be medically evaluated and fulfill the NMDP and FACT criteria for collection of PBSCs. ***Patients: - Patients and donors may be of either gender or any ethnic background. - Patients must have a Karnofsky adult, or Lansky pediatric performance scale status > or = 70%. - At the time of referral for transplantation, patients must have no co-existing medical problems that would significantly increase the risk of the transplant procedure. - Patients must have adequate physical function measured by : --- Cardiac: asymptomatic or if symptomatic then 1) LVEF at rest must be > or = to 50% and must improve with exercise or 2) Shortening Fraction > or = to 29% --- Hepatic: < 5 x ULN SGOT and < 2.0 mg/dl total serum bilirubin. --- Renal: serum creatinine < or = to 1.5 mg/dl or if serum creatinine is outside the normal range, then CrCl > 60-ml/min/1.73 m2 --- Pulmonary: asymptomatic or if symptomatic, DLCO > 50% of predicted (corrected for hemoglobin) - Each patient must be willing to participate as a research subject and must sign an informed consent form. Parent or legal guardians of patients who are minors will sign the informed consent form. Assents will be obtained as age appropriate. - Patients must be available for follow-up evaluations at 30, 60, 180 days post PBSCT and yearly thereafter indefinitely. - Female patients and donors must not be pregnant or breastfeeding at the time of signing consent. Women must be willing to undergo a pregnancy test prior to transplant and avoid becoming pregnant while on study. Other eligibility criteria may apply. - Active CNS leukemic involvement - Female patients who are pregnant (positive serum or urine ß-HCG) or breast-feeding. Women of childbearing age must avoid becoming pregnant while on study. - Active uncontrolled viral, bacterial or fungal infection - Patient seropositive for HIV-I/II; HTLV -I/II Other exclusion criteria may apply. 51378a91998d5beeb193ff03b3e3a808 9192 Donor Umbilical Cord Blood Transplant With or Without Ex-Vivo Expanded Cord Blood Progenitor Cells in Treating Patients With Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, or Myelodysplastic Syndromes II Colleen Delaney, MD, MSc 2603.00 2; 19; 36; 43 Acute Myeloid Leukemia (AML); Chronic Myeloid Leukemia (CML); Hematologic Malignancies; Leukemia Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9192.html http://www.clinicaltrials.gov/ct/search?term=NCT01690520 NCT01690520 This randomized phase II trial studies how well giving donor umbilical cord blood transplant with or without ex-vivo expanded cord blood progenitor cells works in treating patients with acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, or myelodysplastic syndromes. Giving chemotherapy and total-body irradiation before a donor umbilical cord blood transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's cells. When the healthy stem cells and ex-vivo expanded cord blood progenitor cells are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. It is not yet known whether giving donor umbilical cord blood transplant plus ex-vivo expanded cord blood progenitor cells is more effective than giving a donor umbilical cord blood transplant alone. Ages Eligible for Study: 6 Months to 45 Years Genders Eligible for Study: Both - Acute myeloid leukemia: - *High risk first complete remission (CR1) as evidenced by preceding myelodysplastic syndromes (MDS), high risk cytogenetics (for example, monosomy 5 or 7, or as defined by referring institution treatment protocol), >= 2 cycles to obtain complete remission (CR), erythroblastic or megakaryocytic leukemia; >= second complete remission (CR2) - *All patients must be in CR as defined by hematologic recovery and < 5% blasts by morphology within the bone marrow and a cellularity of >= 15% for age - *Patients in which adequate marrow/biopsy specimens cannot be obtained to determine remission status by morphologic assessment, but have fulfilled criteria of remission by flow cytometry, recovery of peripheral blood counts with no circulating blasts, and/or normal cytogenetics (if applicable) may still be eligible; reasonable attempts must be made to obtain an adequate specimen for morphologic assessment, including possible repeat procedures; these patients must be discussed with the principal investigator prior to enrollment - Acute Lymphoblastic Leukemia - *High risk CR1 [for example, but not limited to: t(9;22), t(1;19), t(4;11) or other mixed-lineage leukemia (MLL) rearrangements, hypodiploid]; greater than 1 cycle to obtain CR; CR2 or greater - *All patients must be in CR as defined by hematologic recovery and < 5% blasts by morphology within the bone marrow and a cellularity of >= 15% for age - *Patients in which adequate marrow/biopsy specimens cannot be obtained to determine remission status by morphologic assessment, but have fulfilled criteria of remission by flow cytometry, recovery of peripheral blood counts with no circulating blasts, and/or normal cytogenetics (if applicable) may still be eligible; reasonable attempts must be made to obtain an adequate specimen for morphologic assessment, including possible repeat procedures; these patients must be discussed with the principal investigator prior to enrollment - Chronic myelogenous leukemia excluding refractory blast crisis; to be eligible in first chronic phase (CP1) patient must have failed or be intolerant to tyrosine kinase inhibitor therapy - Myelodysplasia (MDS) International Prognostic Scoring System (IPSS) intermediate (Int)-2 or High risk (i.e., refractory anemia with excess blasts [RAEB], refractory anemia with excess blasts in transformation [RAEBt]) or refractory anemia with severe pancytopenia or high risk cytogenetics; blasts must be < 10% by a representative bone marrow aspirate morphology - Karnofsky (>= 16 years old) >= 70 or Eastern Cooperative Oncology Group (ECOG) 0-1 - Lansky (< 16 years old) >= 60 - Adults: calculated creatinine clearance must be > 60 mL and serum creatinine =< 2 mg/dL - Children (< 18 years old): calculated creatinine clearance must be > 60 mL/min - Total serum bilirubin must be < 3mg/dL unless the elevation is thought to be due to Gilbert's disease or hemolysis - Transaminases must be < 3 x the upper limit of normal - Diffusing capacity of the lung for carbon monoxide (DLCO) corrected > 60% normal - For pediatric patients unable to perform pulmonary function tests, oxygen (O2) saturation > 92% on room air - May not be on supplemental oxygen - Left ventricular ejection fraction > 45% OR - shortening fraction > 26% - Ability to understand and the willingness to sign a written informed consent document Other eligibility criteria may apply. - Uncontrolled viral or bacterial infection at the time of study enrollment - Active or recent (prior 6 month) invasive fungal infection without infectious disease (ID) consult and approval - History of human immunodeficiency virus (HIV) infection - Pregnant or breastfeeding - If =< 18 years old, prior myeloablative transplant within the last 6 months - If > 18 years old prior myeloablative allotransplant or autologous transplant - Extensive prior therapy including > 12 months alkylator therapy or > 6 months alkylator therapy with extensive radiation Other exclusion criteria may apply. 5e29492a9ebe49fd80f6ea413301ece0 9092 Internet and Social-Media Program for Improving Quality of Life in Long-Term Cancer Survivors Who Underwent Stem Cell Transplant III Karen Syrjala, PhD 2605.00 36; 48 Hematologic Malignancies; Lymphoma Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9092.html http://www.clinicaltrials.gov/ct/search?term=NCT01602211 NCT01602211 Researchers are doing this study to examine ways to improve the health of long-term survivors of bone marrow or blood stem cell transplant. Researchers want to know if a survivorship-focused internet program can improve mood, stress, and preventive health care, and provide useful health resources for transplant survivors. In this study, researchers want to compare a survivorship internet program to the standard treatment of currently available internet sites for transplant survivors to learn which works better for people who have received bone marrow or blood stem cell transplants. Patients in this study will either receive immediate access to the survivorship internet program that includes links to existing resources, or will receive links to existing resources and delayed access to the full internet program. All participants will eventually receive access to the survivorship internet program Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Received a transplant at a consortium center for a hematologic malignancy - Currently 2-10 years after first HCT Other eligibility criteria may apply. - Does not have internet and email access; note that survivors otherwise eligible, but excluded from full study participation because of this exclusion, will be asked to fill out a mailed copy of the baseline assessment for use in secondary aims analyses; they will be sent an information form and a copy of the tailored 'My Health Action Plan' health care guideline for transplant survivors also provided to randomized participants - English insufficient to complete baseline patient-reported outcomes (PRO) assessments - Has received treatment for a recurrent or 2nd cancer that required > surgical excision in the past 2 years; (these participants will be ineligible for randomization, but will have intervention site access if they complete baseline PRO assessment) - Scores 20 or above on the patient health questionnaire (PHQ)-8 depression measure (indicating severe depression); these participants will be contacted by a study psychologist to evaluate and provide resources to address their needs (2% of enrollees in our previous study); they will be ineligible for randomization, but will have intervention site access if they complete baseline PRO assessment - Residing in an institution or other living situation where health care decisions are not made by the participant (e.g., hospitalized, prisoners, living in a rehabilitation facility) - Does not complete baseline PRO assessment items required to determine stratification or whether the survivor meets inclusion and exclusion criteria Other exclusion criteria may apply. 78335cc23fc64e4b691b70046d199055 9214 NA Oliver Press, MD, PhD 2609.00 36; 38; 48; 64 Hematologic Malignancies; Hodgkin's Lymphoma; Lymphoma; Non-Hodgkin's Lymphoma (NHL) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9214.html http://www.clinicaltrials.gov/ct/search?term=2609.00 2609.00 76219e793590d4140f0cb3daaabcbf89 9399 Liposomal Cytarabine and Daunorubicin (CPX-351) for Adults with Untreated High-Risk MDS and Non-APL AML at High Risk of Treatment-Related Mortality Pilot Roland Walter, MD 2642.00 2; 36; 43 Acute Myeloid Leukemia (AML); Hematologic Malignancies; Leukemia Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9399.html http://www.clinicaltrials.gov/ct/search?term=NCT01804101 NCT01804101 This clinical trial studies liposomal cytarabine-daunorubicin CPX-351 in treating patients with untreated myelodysplastic syndrome or acute myeloid leukemia. Drugs used in chemotherapy, such as liposomal cytarabine-daunorubicin CPX-351, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Diagnosis of untreated "high-risk" MDS (>= 10% blasts) or AML other than APL with t(15;17)(q22;q12) or variants according to the 2008 World Health Organization (WHO) classification; patients with biphenotypic AML are eligible; outside diagnostic material is acceptable as long as peripheral blood and/or bone marrow slides are reviewed at the study institution and cytogenetic/molecular information is available --- Prior hydroxyurea for AML is permitted but should be discontinued prior to start of CPX-351 treatment --- Azacitidine, decitabine, lenalidomide, and growth factors are permitted for low-risk MDS (< 10% blasts); all treatments for MDS should be discontinued prior to start of CPX-351 treatment - TRM score >= 13.1 as calculated with simplified model - Bilirubin < 2.0 mg/mL x upper limit of normal - Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 4.0 x upper limit of normal - Left ventricular ejection fraction (LVEF) >= 40%, assessed within 28 days prior to registration, e.g. by multi gated acquisition scan (MUGA) scan or echocardiography, or other appropriate diagnostic modality - Patients with symptoms/signs of hyperleukocytosis or white blood cell (WBC) >100,000/uL can be treated with leukapheresis prior to enrollment - Provide signed written informed consent Other eligibility criteria may apply. - Refractory/relapsing blast crisis of chronic myelogenous leukemia (CML) - Concomitant illness associated with a likely survival of < 1 year - Active systemic fungal, bacterial, viral, or other infection, unless under treatment with anti-microbials and controlled/stable, as defined as being afebrile and hemodynamically stable for 24-48 hours Other exclusion criteria may apply. 38e10c73798cd05593d9193bcaafa630 9425 Decitabine Followed By Mitoxantrone Hydrochloride, Etoposide, and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndromes I/II Roland Walter, MD 2652.00 2; 36; 43 Acute Myeloid Leukemia (AML); Hematologic Malignancies; Leukemia Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9425.html http://www.clinicaltrials.gov/ct/search?term=NCT01729845 NCT01729845 This phase I/II trial studies the side effects and best dose of decitabine followed by mitoxantrone hydrochloride, etoposide, and cytarabine and to see how well it works in treating patients with relapsed or refractory acute myeloid leukemia or high-risk myelodysplastic syndromes. Drugs used in chemotherapy, such as mitoxantrone hydrochloride, etoposide, cytarabine, and decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Prior diagnosis of "high-risk" myelodysplastic syndrome (MDS) (>= 10% blasts) or AML other than acute promyelocytic leukemia (APL) with t(15;17) (q22;q12) or variants according to the 2008 World Health Organization (WHO) classification; patients with biphenotypic AML are eligible - Relapsed/persistent disease according to standard criteria requiring salvage therapy; outside diagnostic material is acceptable as long as peripheral blood and/or bone marrow slides are reviewed at the study institution; flow cytometric analysis of peripheral blood and/or bone marrow should be performed according to institutional practice guidelines - Patients with prior autologous or allogeneic hematopoietic cell transplantation (HCT) are eligible if relapse occurs > 180 days post-transplant provided symptoms of graft-versus host disease are well controlled with stable use of immunosuppressive agents - Treatment-related mortality (TRM) score =< 9.2 as calculated with simplified model - Should be off any active therapy for AML with the exception of hydroxyurea for at least 14 days prior to study registration unless patient has rapidly progressive disease, and all grade 2-4 non-hematologic toxicities should have resolved - May have previously received monotherapy with demethylating agents for MDS or AML - May have previously received chemotherapy with MEC for MDS or AML - Patients with symptoms/signs of hyperleukocytosis or white blood cells (WBC) > 100,000/uL can be treated with leukapheresis or may receive up to 2 doses of cytarabine (up to 500 mg/m^2/dose) prior to enrollment - Bilirubin =< 2 x institutional upper limit of normal (IULN) unless elevation is thought to be due to hepatic infiltration by AML, Gilbert's syndrome, or hemolysis (assessed within 7 days prior to registration) - Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum pyruvate glutamate transaminase (SPGT) (alanine aminotransferase [ALT]) =< 2 x IULN unless elevation is thought to be due to hepatic infiltration by AML (assessed within 7 days prior to registration) - Serum creatinine =< 1.5 x IULN (assessed within 7 days prior to registration) - Left ventricular ejection fraction >= 40%, assessed within 28 days prior to registration, e.g. by multi gated acquisition (MUGA) scan or echocardiography, or other appropriate diagnostic modality and no clinical evidence of congestive heart failure; if the patient had anthracycline-based therapy since the most recent cardiac assessment, cardiac evaluation should be repeated if there is clinical or radiographical suspicion of cardiac dysfunction, or if the previous cardiac assessment was abnormal - Women of childbearing potential and men must agree to use adequate contraception - Provide written informed consent Other eligibility criteria may apply. - Refractory/relapsing myeloid blast crisis of chronic myeloid leukemia (CML), unless patient is not considered candidate for tyrosine kinase inhibitor treatment - Concomitant illness associated with a likely survival of < 1 year - Active systemic fungal, bacterial, viral, or other infection, unless under treatment with anti-microbials and controlled/stable, as defined as being afebrile and hemodynamically stable for 24-48 hours - Known hypersensitivity to any study drug - Pregnancy or lactation - Patients may not be receiving any other investigational agents Other exclusion criteria may apply. 30d22b61978ea8f2f10b59e899d30db4 9440 Palliative Care Support for Patients With Hematological Malignancies Undergoing Hematopoietic Cell Transplant Pilot Stephanie Lee, MD, MPH 2659.00 1; 36 Acute Lymphoid Leukemia (ALL); Hematologic Malignancies Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9440.html http://www.clinicaltrials.gov/ct/search?term=NCT01758484 NCT01758484 This pilot clinical trial studies palliative care support for patients with hematological malignancies undergoing hematopoietic cell transplant. Palliative care support may improve quality of life in this patient population. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Written informed consent - English as primary language - Planned autologous or allogeneic hematopoietic cell transplantation - Presence of co-morbidities (hematopoietic cell transplant co-morbidity index [HCT-CI] score 3 or greater), high risk disease (relapse risk > 25%), or a planned type of transplant (human leukocyte antigen [HLA]-mismatched allogeneic or myeloablative) that places the patient at a higher than average risk of non-relapse mortality or relapse Other eligibility criteria may apply. - Major psychiatric diagnosis that impairs cognitive functioning or is not controlled at the time of the approach, as judged by the patient's medical team - First transplant of a planned tandem procedure (the second transplant is eligible) Other exclusion criteria may apply. d27fe24b2ce0f7c7329f5f826c800f89 9511 Chemotherapy in Treating Patients With Myelodysplastic Syndrome Before Donor Stem Cell Transplant (ICT-HCT) II Bart Scott, MD 2661.00 36; 43; 61 Hematologic Malignancies; Leukemia; Myelodysplastic and Myeloproliferative Syndromes (MDS and MPD) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9511.html http://www.clinicaltrials.gov/ct/search?term=NCT01812252 NCT01812252 This clinical trial studies different chemotherapies in treating patients with myelodysplastic syndrome before donor stem cell transplant. Giving chemotherapy before a donor hematopoietic stem cell transplant helps stop the growth of cancer cells before, and may prevent the myelodysplastic syndrome from coming back after the transplant. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Diagnosis of de novo or secondary myelodysplastic syndrome (MDS), including chronic myelomonocytic leukemia, as defined by the 2008 World Health Organization classification system - Patients must have measurable disease requiring cytoreduction, defined as a bone marrow myeloblast count >= 5% and < 20% on morphologic examination - Patients in which adequate marrow/biopsy specimens cannot be obtained to determine disease burden by morphologic assessment, but have fulfilled criteria (abnormal myeloblast count >= 5% and < 20%) by flow cytometry are still be eligible; reasonable attempts must be made to obtain an adequate specimen for morphologic assessment, including possible repeat procedures - Patients must be considered to have an acceptable risk of early mortality with intensive chemotherapy as determined by the attending physician at the time of the initial visit; since the specific therapy within each arm will be determined after randomization, there is no threshold of organ dysfunction or performance status for inclusion; the attending may use metrics such as Treatment Related Mortality Score (TRM) or Karnofsky performance status, in addition to clinical values (age, platelet count, serum albumin, secondary or de novo disease, white blood cell count, peripheral blood blast percentage, and serum creatinine) to determine if a patient should be included - Considered a potential transplant candidate; the attending physician will determine transplant candidacy at the time of initial visit - Human leukocyte antigen (HLA)-typing must be requested by the time of enrollment, but does not need to be resulted to enroll - Males should be willing to use an effective contraceptive method during the study and for a minimum of 6 months after study treatment - Women must be postmenopausal or must be willing to use an acceptable method of contraception to avoid pregnancy for the entire period of the study and for at least 3 months after the study; a postmenopausal woman is defined as a woman who has experienced amenorrhea > 12 consecutive months or a woman on hormone replacement therapy with documented follicle-stimulating hormone (FSH) level > 35 mIU/mL; for patients in whom menopausal state is in question, a negative pregnancy test will be required prior to enrollment - Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent Other eligibility criteria may apply. - A diagnosis of acute promyelocytic leukemia as defined by the 2008 World Health Organization classification system - Previous treatment for MDS or AML with intensive chemotherapy regimen (induction chemotherapy) or hypomethylating agent; previous treatment with iron chelation, growth factors (filgrastim [GCSF], erythropoiesis stimulating agent, or thrombopoietin mimetics), small molecule inhibitors, or immune modulatory drugs (thalidomide, lenalidomide) is acceptable - Use of any anticancer therapy within 2 weeks before study entry with the exception of hydroxyurea - Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo treatment - Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment) - Pregnant or lactating patients - Any uncontrolled or significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results - Clinical evidence suggestive of central nervous system (CNS) involvement with leukemia unless a lumbar puncture confirms the absence of leukemic blasts in the cerebrospinal fluid (CSF) Other exclusion criteria may apply. a2a74107122bc19fdb2d7ecc056ecd07 9521 Lenalidomide With or Without Rituximab in Treating Patients With Progressive or Relapsed Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Prolymphocytic Leukemia, or Non-Hodgkin Lymphoma Previously Treated With Donor Stem Cell Transplant II Raya Mawad 2674.00 36; 43; 48; 64; 123 Hematologic Malignancies; Leukemia; Lymphoma; Non-Hodgkin's Lymphoma (NHL); Mycosis Fungoides/Sezary Syndrome Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9521.html http://www.clinicaltrials.gov/ct/search?term=NCT01831232 NCT01831232 This phase II trial studies how well giving lenalidomide with or without rituximab works in treating patients with progressive or relapsed chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), prolymphocytic leukemia (PLL), or non-Hodgkin lymphoma (NHL). Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving lenalidomide together with or without rituximab may kill more cancer cells Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Understand and voluntarily sign an informed consent form - Able to adhere to the study visit schedule and other protocol requirements - Patients with CLL/SLL/PLL or NHL and who: --- Met the criteria of relapse or progression after allogeneic HCT according to the HCT protocol or the attending discretion and who, --- Not responding to appropriate tapering of immunosuppressive medications - Absolute neutrophil count (ANC) >= 1500/mm^3 or > 1000/mm^3 if ANC has persistently < 1500/ mm^3 for more than 2 weeks - Platelet count (transfusion independent) >= 50,000/mm^3 or >= 20,000/mm^3 if platelet count has persistently < 50,000/mm^3 for more than 2 weeks - Creatinine clearance >= 30ml/min by Cockcroft-Gault formula - Total bilirubin =< 1.5 x upper limit of normal (ULN) or =< 3 x ULN if total bilirubin has been persistently > 1.5 x ULN for more than 2 weeks - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine transaminase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 3 x ULN or =< 5 x ULN if AST or ALT have been persistently > 3 x ULN for more than 2 weeks - Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days and again within 24 hours prior to prescribing lenalidomide for Cycle 1 (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy - All study participants must be registered into the mandatory RevAssist program, and be willing and able to comply with the requirements of RevAssist - Study participants with risk factors for venous thrombo-embolism (VTE), such as previous VTE, cardiac disease, chronic renal insufficiency, and/or poorly controlled diabetes, should be able to comply with some degree of prophylactic anticoagulation using aspirin 81 or 325 mg daily, coumadin, or low molecular weight heparin Other eligibility criteria may apply. - Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from signing the informed consent form - Pregnant or breast feeding females; (lactating females must agree not to breast feed while taking lenalidomide) - Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study - Known hypersensitivity to thalidomide - The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs - Resistance to prior use of lenalidomide, defined as progression on full dose lenalidomide within the first two cycles of therapy - Concurrent use of other anti-cancer agents or treatments - Known seropositive for or active viral infection with human immunodeficiency virus - Karnofsky performance status < 50% - Active grades III or IV acute graft-versus-host disease (GVHD) Other exclusion criteria may apply. 309f4505b52b72a770367d53a02db917 7618 NA Monique Cherrier, PhD 30824 71; 83 Prostate Cancer; Solid Tumors Tom Erickson, MA 206/277-1058 http://depts.washington.edu/wellness/. http://www.fhcrc.org/en/treatment/clinical-trials/detail.7618.html http://www.clinicaltrials.gov/ct/search?term=30824 30824 The purpose of this study is to examine thinking abilities and emotions in survivors of prostate cancer. We are seeking men for two separate parts of this study: 1) Control Group: Survivors of prostate cancer who are 6 months post primary treatment. 2) Treatment Group: Men with prostate cancer who are about to start hormone treatment with androgen deprivation therapy (ADT). Note: For the treatment group, participants must be enrolled in this study BEFORE starting ADT. This is an outpatient study at the Seattle Cancer Care Alliance (SCCA) or Veterans Affairs Medical Center (VA) in Seattle. Participants will complete approximately 6 visits. Each visit will last about 2-3 hours and will include a blood draw. Participants in the Treatment Group will receive either a testosterone gel or a placebo gel, to be used for one month following treatment with ADT. (The placebo gel is an inactive substance.) Participants will receive the gel and instructions in how to use it at the SCCA. 1) Control Group - Survivors of prostate cancer: - More than 6 months have passed since last treatment for prostate cancer - Not currently undergoing cancer treatment 2) Treatment Group - Men with prostate cancer who have not yet started treatment with androgen deprivation therapy (ADT): - Must be eligible for ADT - Must NOT have started ADT yet All participants: - Able to travel to the Seattle Cancer Care Alliance (SCCA) or Veterans Affairs Medical Center (VA) in Seattle - Committed to completing all visits - Primary language is English Other eligibility criteria may apply. - Currently undergoing androgen deprivation therapy (ADT) or other treatments such as chemo or radiotherapy - Evidence of metastatic disease - History of significant neurological disease such as Parkinson's, multiple sclerosis (MS), epilepsy/seizures, or major stroke - History of head injury/trauma - History of alcohol abuse, current alcohol abuse, or other substance abuse - Major psychiatric illness such as schizophrenia or bipolar disorder Other exclusion criteria may apply. 38c79f6ee3de34b5dc956a12b5d66101 6999 Combination Chemotherapy, Intensity-Modulated Radiation Therapy, and Surgery in Treating Patients With Localized Pancreatic Cancer That Can Be Removed By Surgery II Andrew Coveler, MD 6511 28; 66; 83 Gastrointestinal Cancer; Pancreatic Cancer; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.6999.html http://www.clinicaltrials.gov/ct/search?term=NCT00609336 NCT00609336 This phase II trial studies how well giving combination chemotherapy together with intensity-modulated radiation therapy (IMRT) and surgery works in treating patients with localized pancreatic cancer that can be removed by surgery. Drugs used in chemotherapy, such as gemcitabine hydrochloride, docetaxel, capecitabine, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Specialized radiation therapy, such as IMRT, that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Giving more than one drug (combination chemotherapy) together with intensity-modulated radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both -Patients must have histologically or cytologically confirmed diagnosis of localized, resectable or borderline resectable, pancreatic adenocarcinoma T1-T3, N0-N1, M0; stage is determined by helical multi-phase computed tomography (CT) and/or endoscopic ultrasound according to published guidelines resectability is determined by the treating surgeon and published guidelines (National Comprehensive Cancer Network) - Resectable Disease- Head/Body/Tail of pancreas: - *No distant metastases - *Clear fat plane around celiac and superior mesenteric arteries (SMA) - *Patent superior mesenteric vein (SMV) and portal vein (PV) - Borderline Resectable Disease -Head/Body of pancreas: - *Tumor abutment on SMA - *SMV/portal vein impingement or occlusion if involving only a short segment, with open vein both proximally and distally (if proximal vein is occluded up to the portal vein branches then disease is unresectable) - *Colon or mesocolon invasion - *Gastroduodenal artery (GDA) encasement up to origin at hepatic artery - Tail of pancreas: - *Adrenal, colon or mesocolon, or kidney invasion - *Preoperative evidence of biopsy-positive peripancreatic lymph node - No prior therapy for pancreatic cancer - Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%) - Leucocytes >= 3,000/uL - Absolute Neutrophil Count >= 1,500/uL - Platelets >= 100,000/uL - Total Bilirubin: - *If within normal limits (WNL) to =< 2.0, the subject is eligible - *If > 2.0 - < 6.0, subject is eligible IF they have a biliary stent and total bilirubin is decreasing - *If >= 6.0, subject is not eligible - Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase [SGPT]) =< 2.5 X institutional upper limit of normal or =< 1.5 X upper limit of normal (ULN) if alkaline phosphatase (Alk Phos) > 2.5 X ULN or if the subject has a biliary stent and the liver function tests (LFTs) are decreasing the subject is eligible - Creatinine clearance >= 30% - Negative pregnancy test for women of childbearing potential; women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately - Ability to swallow and retain oral medication - Ability to understand and willingness to sign a written informed consent document Other eligibility criteria may apply. - Patients may not be receiving any other investigational agents - Histology other than adenocarcinoma - Patients with permanently unresectable pancreatic adenocarcinoma as determined by the treating physician and published guidelines (National Comprehensive Cancer Network v2.2006 - Unresectable disease - Head of pancreas: - *Distant metastases (includes celiac and/or para-aortic) - *SMA, celiac encasement - *SMV/portal occlusion - *Aortic, inferior vena cava (IVC) invasion or encasement - *Invasion of SMV below transverse mesocolon - Body of pancreas: - *Distant metastases (includes celiac and/or para-aortic); at the discretion of the treating surgeon, body and tail lesions that have positive celiac and/or para-aortic nodes in close vicinity to the primary may be borderline rather than unresectable - *SMA, celiac, hepatic encasement - *SMV/portal extended occlusion - *Aortic invasion - Tail of pancreas: - *Distant metastases (includes celiac and/or para-aortic) - *SMA, celiac encasement - *Rib, vertebral invasion - History of allergic reactions attributed to compounds of similar chemical or biologic composition to gemcitabine, docetaxel, capecitabine, oxaliplatin or other agents used in the study - Patients who have received prior chemotherapy or radiotherapy for the diagnosis of pancreatic cancer - Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements - Inability to comply with study and/or follow-up procedures - Pregnancy or lactation - Human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy Other exclusion criteria may apply. 7cd5bd6bcef2f51f1df52129cc5c0963 7233 Intermittent Chemotherapy With or Without GM-CSF for Metastatic HPRC II Tia Higano, MD 6620 30; 71; 83 Genitourinary Cancer; Prostate Cancer; Solid Tumors Teresa Gambol 206/288-6452 http://www.fhcrc.org/en/treatment/clinical-trials/detail.7233.html http://www.clinicaltrials.gov/ct/search?term=NCT00488982 NCT00488982 This is a two-arm, randomized Phase II study of intermittent chemotherapy with and without GM-CSF. All patients will receive six 21-day cycles of docetaxel 75 mg/m2 on Day 2 of each cycle and 5 mg prednisone twice a day on Days 1-21. Following six cycles of chemotherapy, eligible subjects will be randomized to no maintenance therapy or to maintenance GM-CSF therapy. The GM-CSF group dose schedule will be 250 mcg/m2 SQ daily Days 15-28 every 28 days. Patients in both groups will continue until disease progression at which time GM-CSF will be discontinued and chemotherapy will again be administered. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Male - Age over 18 years - Histologically documented adenocarcinoma of the prostate - Progressive metastatic prostate cancer - Castrate levels of testosterone (<50 ng/ml) must be maintained - Prior hormonal therapy or medications : Patients who are receiving an anti-androgen, secondary hormonal therapy (i.e. ketoconazole, aminoglutethimide, megestrol acetate, diethylstilbestrol), 5-alpha reductase inhibitor (i.e. finasteride (Proscar), dutasteride (Avodart)) or herbal prostate medication (i.e. saw palmetto, PC-SPES, PC-PLUS) must discontinue the drug by the date of initiation of chemotherapy on study - = 4 weeks since major surgery and fully recovered - = 4 weeks since any prior radiation with any toxicity attributable to radiation resolved to =grade 1 - = 8 weeks since the last dose of strontium or samarium - Sexually active patients must agree to use adequate contraception - Karnofsky Performance Status = 60% - Life expectancy >12 weeks - Required initial laboratory values Absolute neutrophil count > 1500/ul Platelets > 100,000/ul Hemoglobin > 8.0 g/dl Creatinine = 2.0 X upper limit of normal Bilirubin =upper limit of normal (ULN) - AST/ALT/alkaline phosphatase: - AST AND ALT AND alkaline phosphatase must be within the range allowing for eligibility In determining eligibility, the more abnormal of the 2 values (AST or ALT should be used. An abnormal alkaline phosphatase must be attributed to liver dysfunction and not metastatic bone involvement (i.e elevated GGTP or evidence of liver metastases) Inclusion criteria for late enrolling patients: - Age over 18 years - Histologically documented adenocarcinoma of the prostate - =3 cycles of prior docetaxel chemotherapy for metastatic disease permitted prior to enrollment - Docetaxel must have been administered on an every 3 week schedule - Each docetaxel dose must have been between 60 and 75 mg/m2 - Castrate levels of testosterone <50 ng/mL - Daily use of other steroids (hydrocortisone, dexamethasone) instead of prednisone or no steroids, is permitted up until time of enrollment - A PSA level must have been documented within 6 weeks of initiating docetaxel chemotherapy Other eligibility criteria may apply. - Prior systemic chemotherapy for prostate cancer, other than q 3-week docetaxel/prednisone. Prior neoadjuvant or adjuvant chemotherapy is permitted if there was no evidence of disease relapse within 12 months of the last dose of chemotherapy. - >3 cycles of q3 week docetaxel/prednisone chemotherapy has already been administered to the patient - Peripheral neuropathy >grade 1 - Prior immunotherapy including systemic GM-CSF or vaccines utilizing GM-CSF; prior G-CSF support of chemotherapy-related neutropenia is permitted - Prior biologic agents (i.e.,anti-angiogenic agents, anti-EGFR inhibitors)= 4 weeks prior to registration - More than two prior therapies with an investigational agent, completed = 4 weeks prior to enrollment (no prior immunotherapeutics are allowed) - Myocardial infarction or significant change in anginal pattern within the last 6 months, symptomatic congestive heart failure (NYHA Class III or higher) or uncontrolled cardiac arrhythmia - Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, HIV-positive patients receiving combination anti-retroviral therapy are excluded - Patients with a history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80 will be excluded - Poorly controlled diabetes (fasting blood glucose >250) despite optimization of medical therapy Exclusion criteria for late enrolling patients: - Prior immunotherapy including systemic GM-CSF or vaccines utilizing GM-CSF; prior G-CSF support for chemotherapy-related neutropenia is permitted - Delay of =6 weeks between any 2 chemotherapy cycles prior to enrollment on study - Cumulative delays =8 weeks between chemotherapy cycles prior to enrollment on study Other exclusion criteria may apply. 78702f7c2e010d5515a3af4a58224242 7196 Paclitaxel Albumin-Stabilized Nanoparticle Formulation and Bevacizumab Followed By Bevacizumab and Erlotinib Hydrochloride in Treating Patients With Metastatic Breast Cancer II Jennifer Specht, MD 6628 13; 83 Breast Cancer; Solid Tumors Breast Research Study Line, Jonathan Khanjian breastresearch@seattlecca.org 206/288-7427 https://www.seattlecca.org/clinical-trials/breast-cancer-list.cfm http://www.fhcrc.org/en/treatment/clinical-trials/detail.7196.html http://www.clinicaltrials.gov/ct/search?term=NCT00733408 NCT00733408 This phase II trial is studying how well giving paclitaxel albumin-stabilized nanoparticle formulation together with bevacizumab followed by bevacizumab and erlotinib hydrochloride work in treating patients with metastatic breast cancer. Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving paclitaxel albumin-stabilized nanoparticle formulation together with bevacizumab and erlotinib hydrochloride may kill more tumor cells. Genders Eligible for Study: Both - Have histologically confirmed invasive breast cancer that is estrogen receptor (ER) negative, progesterone receptor (PR) negative and human epidermal growth factor receptor (HER)-2 non-overexpressing - Be receiving first-line therapy for metastatic disease - Measurable disease by Response Evaluation Criteria In Solid Tumors (RECIST) criteria; Xrays, scans or physical examinations used for tumor measurement must have been completed within 28 days prior to registration; Xrays, scans or other tests for assessment of non-measurable disease must have been performed within 42 days prior to registration - OR - Non-measurable disease only, with rising serum CA15-3 or CA 27.29 or carcinoembryonic antigen (CEA) documented by two consecutive measurements taken at least 14 days apart with the most recent measurement being within 42 days prior to registration - AND the second CA 15-3 or CA 27.29 or CEA value must have at least a 20% increase over the first and for CA 15-3 or CA 27.29 be greater than or equal to 40 units/mL or for CEA be greater than or equal to 4 ng/mL - If of childbearing potential must have a negative pregnancy test and use an effective method to avoid pregnancy for the duration of the trial and for at least 6 months after completion of study therapy if able to bear children - Patients must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional standards and federal guidelines Other eligibility criteria may apply. - Recurrent disease within 12 months after completion of adjuvant chemotherapy containing a weekly taxane - Central nervous system (CNS) metastases - Pre-existing nephritic syndrome - Serious intercurrent medical or psychiatric illness including serious active infection - Inadequately controlled hypertension (defined as systolic blood pressure > 150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications) - Any prior history of hypertensive crisis or hypertensive encephalopathy - New York Heart Association (NYHA) Grade II or greater congestive heart failure - History of myocardial infarction or unstable angina within 6 months prior to study enrollment - History of stroke or transient ischemic attack within 6 months prior to study enrollment - Significant vascular disease (e.g., aortic aneurysm, aortic dissection) - Symptomatic peripheral vascular disease - Evidence of bleeding diathesis or coagulopathy - Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study - Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment - History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment - Serious, non-healing wound, ulcer, or bone fracture - Proteinuria at screening as demonstrated by either: urine protein:creatinine (UPC) ratio >= 1.0 at screening OR urine dipstick for proteinuria >= 2+ (patients discovered to have >= 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate =< 1g of protein in 24 hours to be eligible) - Known hypersensitivity to any component of bevacizumab Other exclusion criteria may apply. e1a1adc5eea42dc5b373f94170b99400 7237 Vaccine Therapy in Treating Patients With Stage IV Breast Cancer I/II Nora Disis, MD 6658 13; 83 Breast Cancer; Solid Tumors Tumor Vaccine Group, Study Line 206/543-6620 http://depts.washington.edu/tumorvac/ http://www.fhcrc.org/en/treatment/clinical-trials/detail.7237.html http://www.clinicaltrials.gov/ct/search?term=NCT00791037 NCT00791037 PRIMARY OBJECTIVES: - To evaluate how safe giving escalating doses of T cells into patients with advanced HER2-positive breast cancer is. - To look at how much HER2 specific T cell immunity can be boosted or generated in patients. INCLUSION CRTIERIA: - Patients with HER2-positive Stage IV breast cancer that have been maximally treated and not achieved a complete remission - Patients must have stable or slowly progressive disease, measurable as described below: -- a) Extraskeletal disease that can be accurately measured = 10 mm by standard imaging techniques that can include but not limited to CT, PET, PET/CT, MRI -- b) Skeletal or bone-only disease which is measurable by FDG PET or PET/CT imaging will also be allowed - Patients can be currently receiving trastuzumab (herceptin) and/or lapatinib (Tykerb) and/or hormonal therapy and/or bisphosphonate therapy - HER2 overexpression in the primary tumor or metastasis by: -- a) IHC of 2+ or 3+, or -- b) Documented gene amplification by fluorescence in situ hybridization (FISH) analysis -- c) If overexpression is 2+ by IHC, then patients must have HER2 gene amplification documented by FISH - Subjects must have a Performance Status Score (SWOG/Zubrod Scale) = 0- 2 - Patients must be off all immunosuppressive treatments such as chemotherapy or systemic steroid therapy a minimum of 14 days prior to the first vaccination - Patients on trastuzumab (herceptin) and/or lapatinib (Tykerb) must have a baseline LVEF measured by MUGA or echocardiogram (ECHO) equal to or greater than the lower limit of normal for the facility within 90 days of eligibility determination - Subjects must be = 18 years old - Men and women of reproductive ability must agree to contraceptive use during the entire study period - Patients must have an expected survival of 6 months - White blood cell (WBC) = 3000/mm3 - Absolute neutrophil count (ANC) = 1000/mm3 - Hemoglobin (Hgb) = 10 mg/dl - Platelets = 75,000mm3 - Serum creatinine = 2.0 mg/dl or creatinine clearance > 60 ml/min - Total bilirubin = 2.5 mg/dl - Aspartate Aminotransferase (AST)/Serum Glutamic Oxaloacetic Transaminase (SGOT) = 3 times ULN Other eligibility criteria may apply. EXCLUSION CRITERIA: - Patients with any of the following cardiac conditions: -- a) symptomatic restrictive cardiomyopathy -- b) unstable angina within 4 months prior to enrollment -- c) New York Heart Association functional class III-IV heart failure on active treatment - Patients with any contraindication to receiving rhuGM-CSF based products - Patients with any clinically significant autoimmune disease uncontrolled with treatment - Patients with a history of brain metastases must have a stable head imaging study within 30 days of eligibility determination ----- Specifically, patients with active brain metastases will not be eligible for study - Patients who are simultaneously enrolled in any other treatment study - Pregnant or breast-feeding women Other exclusion criteria may apply. ec6264f97c5c160c2fac9ab469739080 7666 Vorinostat in Patients With Primary Cutaneous T-Cell Lymphoma II Andrei Shustov, MD 6914 36; 48; 64; 123 Hematologic Malignancies; Lymphoma; Non-Hodgkin's Lymphoma (NHL); Mycosis Fungoides/Sezary Syndrome Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.7666.html http://www.clinicaltrials.gov/ct/search?term=NCT00958074 NCT00958074 The purpose of this research study is to determine the safety and effects, good or bad, of the drug vorinostat in subjects with primary cutaneous T-cell lymphoma (CTCL) who have not received any previous treatment. The use of vorinostat in subjects who have not received any previous treatment for CTCL is experimental. Vorinostat is currently approved by the FDA for patients with previously treated CTCL, and is prescribed at a specific dose level. For some patients the standard dose may be too low, while for other patients this dose is too high. In this research study, some participants will start vorinostat at the standard dose and other participants will start vorinostat at a lower dose. The dose that each participant starts with will depend on his or her age. The dose level may be changed during the study based on how the participant is tolerating vorinostat. Study participants will receive study treatment with vorinostat for about 8 to 9 months. Vorinostat is taken as a pill, by mouth. During the treatment period, participants will come to the Seattle Cancer Care Alliance (SCCA) outpatient clinic every 2 to 4 weeks. After the end of study treatment, we would like participants to visit the clinic for follow-up every 2 months for 2 years. If participants are not able to come to the clinic after the end of treatment for follow-up visits, we will contact participants by phone. - 18 years of age or older - Diagnosis of CTCL (stages IB, IIA, IIB, III, or IVA) including mycosis fungoides and/or Sezary syndrome - No previous treatment, except for single agent Targretin - Adequate organ function Other eligibility criteria may apply. - Disease has progressed beyond the skin—CTCL involvement (M1) (CTCL stage IVB) - Previous systemic therapy, total skin electron beam (TSEB) therapy or extracorporeal photopheresis (ECP) Other exclusion criteria may apply. 0b15467427b4760f914bf0df7ceea23f 7702 Molecular Correlates of Sensitivity and Resistance to Therapy in Prostate Cancer NA Robert Montgomery, MD 6932 30; 71; 83 Genitourinary Cancer; Prostate Cancer; Solid Tumors Robert Montgomery, MD 206/598-0860 http://www.fhcrc.org/en/treatment/clinical-trials/detail.7702.html http://www.clinicaltrials.gov/ct/search?term=NCT01050504 NCT01050504 This is a correlative tissue protocol to collect primary and metastatic prostate cancer specimens in order to discover new biomarkers, potential drug targets, study androgen axis signaling, and evaluate resistance developing in response to systemic therapy. Analysis of acquired specimens will provide the basis for the development of improved systemic therapy for prostate cancer patients. The mechanisms for conversion of treatment-sensitive to treatment-resistant prostate cancer are poorly understood. An improved understanding of the mechanisms of resistance to drugs targeting prostate cancer will allow design and testing of new therapeutic agents. With the advent of genomics and proteomics, which enable experiments to be conducted in parallel and on a large scale, one approach to identifying targets in cancer is to compare a statistically significant number of healthy tissues samples with cancerous tissue samples, and measure differences in DNA sequence patterns, gene expression patterns including microRNAs/noncoding RNA, patterns in protein levels or differences in metabolic products. Once individual or sets of differences have been established, the next challenge is to determine which differences are normal variations in pattern; which changes are causing the cancer cell to divide or survive in an unchecked manner; and which are repercussions of the causative change. Hypotheses for "lead targets" are arrived at through statistical analyses and validation experiments in both test tubes and in animal models of disease. These experiments are costly and intensive undertakings, but have generated an enormous amount of useful information and improved the investigators' collective understanding of how tumors develop, grow and survive. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Male Study Population >/=18 years of age, local (prostate or prostate bed) recurrent CRPC or metastatic disease to soft tissue or bone at sites accessible to biopsy with minimal risk of complications, Platelet count >50,000; WBC >1,500, Hgb >8.0, INR<1.5; PTT<45 - One of the following: - Metastatic castration sensitive prostate cancer Castration resistant prostate cancer as defined by serum testosterone < 50 ng/ml and one of the following: - PSA level of at least 2 ng/ml that has risen on at least 2 successive occasions at least 1 week apart. - Evaluable disease progression by modified RECIST - Progression of metastatic bone disease on bone scan with > 2 new lesions Inclusion Criteria: - 18 years of age or older and ability to adequately understand and give informed consent - Local (prostate or prostate bed) recurrent CRPC or metastatic disease to soft tissue or bone at sites accessible to biopsy with minimal risk of complications - Platelet count >50,000; WBC >2,000, Hgb >8.0, INR<1.5; PTT<45 - No history of excessive unexplained bleeding from previous surgery One of the following: 1) Metastatic castration sensitive prostate cancer or; 2) Castration resistant prostate cancer as defined by serum testosterone < 50 ng/ml and one of the following: 3) PSA level of at least 2 ng/ml that has risen on at least 2 successive occasions at least 1 week apart. Evaluable disease progression by modified RECIST (Response Evaluation Criteria in Solid Tumors) 4) Progression of metastatic bone disease on bone scan with > 2 new lesions Other eligibility criteria may apply. - Patients unable to stop chronic anticoagulation with warfarin or lovenox for less than 3 days - Serious or uncontrolled infection - Treatment with a VEGF inhibitor (such as Avastin) within the past 28 days. Other exclusion criteria may apply. ff95b55b006391fdbe21cbd7a3fefd20 7767 High-dose Methotrexate and Liposomal Cytarabine in Treating Patients With CNS Metastases From Breast Cancer II Maciej Mrugala, MD, PhD 6954 13; 16; 83 Breast Cancer; Central Nervous System (CNS); Solid Tumors Fereshteh Assadian 206/288-6693 http://www.fhcrc.org/en/treatment/clinical-trials/detail.7767.html http://www.clinicaltrials.gov/ct/search?term=NCT00992602 NCT00992602 This phase II trial is studying how well giving high-dose methotrexate together with liposomal cytarabine works in treating patients with central nervous system (CNS) metastases from metastatic breast cancer. Drugs used in chemotherapy, such as methotrexate and liposomal cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving high-dose systemic methotrexate with intra-cerebral spinal fluid (CSF) liposomal cytarabine may kill more tumor cells. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Female - Women who are not pregnant (contraception must be used throughout the study) - Diagnosis of breast cancer with metastases to CNS (regardless of receptor status), leptomeningeal disease must be present with/without parenchymal brain involvement - Ability to provide informed consent - No prior treatment with whole brain radiotherapy (WBRT) - If patient received stereotactic radiosurgery (SRS) prior to enrollment it must be well documented which lesions were treated and index lesions (untreated) for follow up must be identified, no treatment with SRS will be permitted while on the study - CNS disease must be documented by magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) cytology - Karnofsky Performance Status > 60 - White blood cells (WBC) > 3.0 K - Absolute neutrophil count (ANC) > 1.5 K - Platelets (PLT) > 100 K - Hematocrit (HCT) > 30% - Acceptable renal function (glomerular filtration rate [GFR] >= 60 mL/min) - Acceptable liver function (see exclusion criteria) - Well controlled systemic disease - Therapy for systemic disease allowing for addition of systemic HD-MTX and IT Depocyt (in general patients receiving trastuzumab or lapatinib at the time of enrollment will be allowed to continue); bisphosphonates (i.e., zoledronic acid) and denosumab will be allowed; other non-CNS active chemotherapies might be allowed if no known interactions with study drugs are present; this will be reviewed on case-by-case basis - Mini-mental status examination score of 24 or above Other eligibility criteria may apply. - Serum bilirubin > 1.5 x the upper limit of reference range (ULRR) - Serum creatinine > 1.5 x ULRR or creatinine clearance =< 60 mL/minute (calculated by Cockcroft-Gault formula) - Potassium, < 3.7 mmol/L despite supplementation; serum calcium (ionized or adjusted for albumin,) or magnesium out of normal range despite supplementation - Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 x ULRR - Alkaline phosphatase (ALP) > 2.5 x ULRR or > 5x ULRR if judged by the investigator to be related to liver metastases - Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the Investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol - Patients with known pleural effusion or ascites - Prior treatment with whole brain radiotherapy, prior treatment with stereotactic radiosurgery (SRS) is allowed under conditions provided in the inclusion criteria - Previous allergic or adverse reaction to methotrexate or cytarabine - Prior treatment with systemic HD-MTX or IT liposomal cytarabine - Prior IT therapy of any kind - Women who are currently pregnant or breast feeding - Previous or current malignancies of other histologies within the last 5 years, with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin - Receipt of any investigational agents within 30 days prior to commencing study treatment - Last dose of prior chemotherapy discontinued less than 4 weeks before the start of study therapy; patients who had no toxicities with prior chemotherapy can start study treatment earlier than 4 weeks - Last radiation therapy to the brain in the form of SRS within the last 2 weeks before the start of study therapy - Any unresolved toxicity greater than Common Toxicity Criteria (CTC) grade 1 from previous anti-cancer therapy - Previous enrollment in the present study - Major surgery within 4 weeks prior to starting therapy, Ommaya reservoir can be used for introduction of chemotherapy within 48-72 hours after placement Other exclusion criteria may apply. 2fbe06cc83d73af9a6c30ef19988eeca 7814 A Trial Using Novel Markers to Predict Malignancy in Elevated-Risk Women NA Nicole Urban, Sc.D., ScD 6973 65; 83 Ovarian Cancer; Solid Tumors Kate Watabayashi 206/667-5624 http://www.fhcrc.org/en/treatment/clinical-trials/detail.7814.html http://www.clinicaltrials.gov/ct/search?term=6973 6973 Purpose The Novel Markers Trial will compare the safety, feasibility and effectiveness of two different epithelial ovarian cancer screening strategies that use CA125 and add HE4 as either a first or second line screen. This study is the next step in a larger research effort to develop a blood test that can be used as a screening method for the early detection of epithelial ovarian cancer. ***Contact: Kate Watabayashi 800-328-1124 kwatabay@fhcrc.org ***Fred Hutchinson Cancer Research Center Recruiting-Seattle, Washington, United States, 98109 Ages Eligible for Study: 25 Years to 80 Years Genders Eligible for Study: Female Inclusion Criteria: *Risk Group 1, Women ages 25 - 80: - The subject has tested positive for a deleterious germ line mutation in BRCA1 or BRCA2. *Risk Group 2, Women ages 35 - 80, Pedigree conditions can be satisfied by multiple primary cancers in the same person: -- The subject has a personal history of breast cancer diagnosed before or at age 50. -- OR the subject has a personal history of bilateral breast cancer -- OR the subject has one first-degree relative with breast cancer diagnosed before or at age 50. -- OR the subject has two breast cancers in the first or second degree relatives, same lineage, with at least one breast cancer diagnosed before or at age 50. -- OR the subject has three or more first or second degree relatives, same lineage, with breast cancer diagnosed at any age. -- OR The family contains at least one ovarian cancer diagnosed at any age in the first or second degree relatives. -- OR the subject is of Ashkenazi ancestry and has had breast cancer diagnosed at any age. -- OR The subject is of Ashkenazi Jewish ethnicity and has one first or second degree relative with breast cancer diagnosed at any age (must be in the same lineage as the Ashkenazi ancestry) -- OR The subject has a male relative with breast cancer diagnosed at any age -- OR The subject has a personal history of a positive genetic test result for a deleterious germline mutation in the P53 gene. -- OR The subject has tested positive for a deleterious germline mutation in one of the DNA mismatch repair (MMR) genes associated with the Hereditary Non-Polyposis Colorectal Cancer Syndrome (HNPCC, also known as Lynch Syndrome) The MMR genes include MLH1, MSH2, MSH6 and PMS2. -- OR the subject has a first or second degree relative with an identified deleterious germline BRCA1 or BRCA2 mutation, but has not yet undergone testing herself. -- OR the subject has a first or second degree relative with an identified deleterious germline MMR gene mutation, but has not yet undergone testing herself. -- OR Probability of carrying a BRCA1 or BRCA2 mutation given family pedigree of breast and ovarian cancers exceeds 20% by any existing BRCA mutational probability model. *Risk Group 3, Women ages 45 - 80: -- Have measurement of CA125, HE4, MMP7 or Mesothelin exceeding the 95th percentile; -- OR have a relative risk of at least 2 based on the EpiRisk logistic regression model including age, family history, and other risk factors. Other eligibility criteria may apply. Exclusion Criteria: - Removal of both ovaries for any reason. - History of ovarian, fallopian tube cancer or peritoneal carcinomatosis. - Currently pregnant. - Unable or unwilling to provide informed consent. - Unwilling to provide the name of a physician. - Unwilling to sign informed consent and/or medical records release form. - Current untreated malignancy (other than non-melanoma skin cancer). - Currently receiving adjuvant chemotherapy or radiation therapy for cancer (except tamoxifen or aromatase inhibitors +/- lupron). Patients who are being treated may enroll 3 months after completion of last treatment. - Intraperitoneal surgery within the last 3 months (laparoscopy or laparotomy). - A medical condition that would place subject at risk as a result of the blood donation, including but not limited to bleeding disorders, chronic infectious disease, emphysema or serious anemia. - Subject has a family member who is a carrier of a BRCA or MMR gene mutation and the subject has undergone genetic testing that included the family mutation and no mutation was found, and there are no cases of ovarian cancer in the family. Other exclusion criteria may apply. 562ac45444ada4b52bfc7d2b39664c0a 7883 A Placebo-Controlled Study of Saracatinib (AZD0530) in Patients With Recurrent Osteosarcoma Localized to the Lung II Robin Jones 7008 10; 77; 83 Bone Cancer; Sarcoma; Solid Tumors Cristina Galer 206/288-7537 http://www.fhcrc.org/en/treatment/clinical-trials/detail.7883.html http://www.clinicaltrials.gov/ct/search?term=NCT00923286 NCT00923286 The purpose of this study is to determine how long patients who undergo complete surgical removal of recurrent osteosarcoma in the lung will remain free of cancer after taking Saracatinib compared to patients taking placebo (a sugar pill). Ages Eligible for Study: 15 Years to 74 Years Genders Eligible for Study: Both - Patient had recurrence of osteosarcoma, localized to the lungs, had complete surgical removal of all lung nodules are eligible for enrollment. - Patient with suspected recurrence of osteosarcoma but who has not had surgery is eligible for enrollment but will not be randomized to receive study medication until deemed fully eligible following surgical removal of all lung nodules. - Patient had histological confirmed diagnosis of osteosarcoma of the recurrent sample. - Patient had recurrence of osteosarcoma in the lung following standard therapy including: adriamycin, cisplatin, ifosfamide and methotrexate. - Patient is = 15 and < 75 years of age. - Weight = 34 kg. - ECOG performance score of 0-2. - Adequate bone marrow function. - Adequate renal function. - Adequate hepatic function. - Adequate cardiac function. - Women of childbearing potential must have had a negative pregnancy test (urine or serum) = 7 days prior to enrollment, and willingness to use an acceptable method of contraception during participation in the study and for 3 months after the last dose. - Randomization must occur = 6 weeks after complete surgical resection. - Patient or legal guardian has signed informed consent. Other eligibility criteria may apply. - Presence of metastatic disease in other locations in addition to the lung. - Disruption of the lung pleura by tumor. - Paget's disease. - Patient currently using, or has previously used CYP3A4 inducers or inhibitors within 2 to 14 days prior to the initiation of oral therapy. - Known hypersensitivity to other Src/Abl non-receptor kinase inhibitors. - Evidence of interstitial lung disease. - Any concurrent condition which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol. - Myocardial infarction within one year prior to study entry. - Bleeding diathesis, resulting in symptomatic bleeding. - Patient is pregnant or nursing/breast-feeding. - Patient received chemotherapy, biological or investigational agent = 28 days prior to enrollment. - Patient experiencing unresolved toxicity = CTCAE grade 2 (except alopecia) from previous agents. Other exclusion criteria may apply. 69ef2bc3367794248c274c2d12efa03c 8140 Multicenter Selective Lymphadenectomy Trial II (MSLT-II) III David Byrd, MD 7108 52; 83 Melanoma; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8140.html http://www.clinicaltrials.gov/ct/search?term=NCT00389571 NCT00389571 Purpose Subjects must be diagnosed with melanoma. All subjects receive sentinel lymphadenectomy. If the subject is sentinel node positive and meets study requirements, the subject is randomized to receive either (1) completion lymphadenectomy (2) observation with nodal ultrasound. Subjects are then followed for 10 years. Ages Eligible for Study: 18 Years to 75 Years Genders Eligible for Study: Both - Ability to provide informed consent. - Between 18 and 75 years of age. - Have a primary melanoma that is cutaneous (including head, neck, trunk, extremity, scalp, palm, sole, subungual skin tissues). - Have clear margins following WLE. - ECOG performance status 0-1. - Life expectancy of at least 10 years from the time of diagnosis, not considering the melanoma in question, as determined by the PI. - Willing to return to the MSLT-II center for follow up examinations and procedures as outlined in the protocol. - Randomization and/or CLND (as appropriate to randomization arm) must be completed no more than 120 days following the diagnostic biopsy of the primary melanoma. - Have a melanoma-related tumor-positive SN, determined by either of the following methods: 1) Diagnosis of tumor-positive SN by MSLT-II center institutional pathologist by either H&E or IHC (using S-100, Mart-1, and HMB-45). 2) Diagnosis of tumor-positive SN by RT-PCR analysis performed at JWCI, provided the primary melanoma fits into one of the following categories: 2a) Breslow thickness of 1.20 mm or greater and Clark Level III. 2b) Clark Level IV or V, regardless of Breslow thickness 3b) Ulceration, regardless of Breslow thickness or Clark level Other eligibility criteria may apply. - History of previous or concurrent (i.e., second primary) invasive melanoma. - Primary melanoma of the eye, ears, mucous membranes or internal viscera. - Physical, clinical, radiographic or pathologic evidence of satellite, in-transit, regional, or distant metastatic disease. - Any additional solid tumor or hematologic malignancy during the past 5 years except T1 skin lesions of squamous cell carcinoma, basal cell carcinoma, or uterine cervical cancer. - Skin grafts, tissue transfers or flaps that have the potential to alter the lymphatic drainage pattern from the primary melanoma to a LN basin. - Allergy to vital blue dye or any radiocolloid. - Inability to localize 1-2 SN drainage basins via LM (e.g., no basins found, more than 2 basins found, proximity of the primary melanoma to the regional draining basin, etc.) - CLNDs or SLs (before evaluation of the current melanoma) that may have altered the lymphatic drainage pattern from the primary cutaneous melanoma to a potential LN basin. - Organic brain syndrome or significant impairment of basal cognitive function or any psychiatric disorder that might preclude participation in the full protocol, or be exacerbated by therapy (e.g., severe depression). - Melanoma-related operative procedures not corresponding to criteria described in the protocol. - Primary or secondary immune deficiencies or known significant autoimmune disease. - History of organ transplantation. - Oral or parenteral immunosuppressive agents (not topical or inhaled steroids) at any time during study participation or within 6 months prior to enrollment. - Pregnant or lactating women. - Participation in concurrent experimental protocols or alternative therapies that might confound the analysis of this trial. Adjuvant therapy protocols after recurrence are acceptable. Other exclusion criteria may apply. db6320c33718ee34f7376cff3a6f244e 8222 Veliparib, Cisplatin, and Vinorelbine Ditartrate in Treating Patients With Recurrent and/or Metastatic Breast Cancer I John Thompson, MD 7161 13; 83 Breast Cancer; Solid Tumors Phase 1 Program, Study Line phase1@u.washington.edu 206/288-7551 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8222.html http://www.clinicaltrials.gov/ct/search?term=NCT01104259 NCT01104259 This phase I trial studies the side effects and best dose of veliparib (ABT-888) when given together with cisplatin and vinorelbine ditartrate in treating patients with recurrent and/or metastatic breast cancer. Veliparib may stop the growth of some tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cisplatin and vinorelbine ditartrate, work in different ways to stop the growth of tumor cells, either by killing them or stopping them from dividing. Giving veliparib together with combination chemotherapy may kill more tumor cells. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Recurrent and/or metastatic breast cancer - Subjects must meet at least one of the following two criteria: *Histologically confirmed primary or metastatic site that is estrogen receptor (ER)-negative (less than 10%), progesterone receptor (PR)-negative (less than 10%), and human epidermal growth factor receptor (HER)2 non-over expressing by immunohistochemistry (IHC) (0, 1) or non-amplified by fluorescence in situ hybridization (FISH) *Confirmed BRCA1 or BRCA2 mutation associated breast cancer - Subjects must have measurable disease, defined as at least one lesion that can be measured in at least one dimension with a minimum size of: longest diameter >= 10 mm (computed tomography [CT] scan slice thickness no greater than 5 mm); 10 mm caliper measurement by clinical exam; to be considered pathologically enlarged and measurable, a lymph node must be >= 15mm in short axis when assessed by CT scan - Subjects may have had any number of prior chemotherapy, endocrine therapy, immunologic, or biologic regimens for metastatic breast cancer - Performance status >= 60% on the Karnofsky scale (Eastern Cooperative Oncology Group [ECOG] =< 2) - Absolute neutrophil count (ANC) >= 1,500/mm^3 (1.5 x 10^9/L) - Platelets >= 100,000/mm^3 (100 x 10^9/L) - Hemoglobin >= 9.0 g/dL - Serum creatinine =< 1.5 x upper normal limit of institution's normal range OR creatinine clearance >= 50 mL/min/1.73m^2 for subjects with creatinine levels above institutional normal - Hepatic function: Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =< 2.5 x the upper normal limit of institution's normal range; for subjects with liver metastases, AST and/or ALT < 5 x the upper normal limit of institution's normal range - Bilirubin =< 1.5 x the upper normal limit of institution's normal range; subjects with Gilbert's Syndrome may have a bilirubin > 1.5 x the upper normal limit of institution's normal range - Partial thromboplastin time (PTT) must be =< 1.5 x the upper normal limit of institution's normal range and International Normalized Ratio (INR) < 1.5; subjects on anticoagulant (such as coumadin) will have PTT and INR as determined by the Investigator - Women of childbearing potential must agree to use adequate contraception (one of the following listed below) prior to study entry, for the duration of study participation and for 90 days following completion of therapy; women of childbearing potential must have a negative serum pregnancy test within 21 days prior to initiation of treatment and/or be confirmed as having postmenopausal status; criteria for determining menopause include any of the following: prior bilateral oophorectomy; age >= 60 years; age < 60 years and amenorrheic for at least 12 months in the absence of chemotherapy, endocrine therapy, or ovarian suppression and follicle-stimulating hormone (FSH) and estradiol in the postmenopausal range: *Total abstinence from sexual intercourse (minimum one complete menstrual cycle) *Vasectomized partner of female subjects *Hormonal contraceptives (oral, parenteral or transdermal) for at least 3 months prior to study drug administration *Double-barrier method (condoms, contraceptive sponge, diaphragm or vaginal ring with spermicidal jellies or cream) *Intra-Uterine Device (IUD) - Male subjects (including those who are vasectomized) whose partners are pregnant or might be pregnant must agree to use condoms for the duration of the study and for 90 days following completions of therapy - Radiation therapy of a non-target lesion must have been completed at least 2 weeks prior to the enrollment date - Subjects with known brain metastases must have clinically controlled neurologic symptoms, defined as surgical excision and/or radiation therapy followed by 14 days of stable neurologic function prior to the first dose of study drug - Ability to understand and the willingness to sign a written informed consent document Other eligibility criteria may apply. - Subject has received any anti-cancer therapy including chemotherapy, immunotherapy, biologic or any investigational therapy within either 28 days or 5 half lives of a targeted therapy (whichever is shorter), prior to study drug administration; subjects receiving hormone therapy, bisphosphonates, denosumab or luteinizing-hormone-releasing hormone (LHRH)-agonists are eligible; subjects who have not recovered to within one grade level (not to exceed Grade 2) of their baseline following a significant adverse event or toxicity attributed to prior anti-cancer treatment are excluded - Subjects with a known hypersensitivity to platinum compounds or vinorelbine - Subjects with baseline peripheral neuropathy that exceeds Grade 1 - Clinically significant and uncontrolled major medical condition(s) including but not limited to: * Active uncontrolled infection * Symptomatic congestive heart failure * Unstable angina pectoris or cardiac arrhythmia * Psychiatric illness/social situation that would limit compliance with study requirements * Any medical condition, which in the opinion of the study investigator, places the subject at an unacceptably high risk for toxicities * Subject's with significant fluid retention, including ascites or pleural effusion, may be allowed at the discretion of the Principal Investigator - Subject is pregnant or lactating Other exclusion criteria may apply. 9a14fbdcc0e791a5df39c8f0f6a43c47 8370 Interleukin-12 Gene and in Vivo Electroporation-Mediated Plasmid DNA Vaccine Therapy in Treating Patients With Merkel Cell Cancer II Shailender Bhatia, MD 7248 81; 83 Skin Cancer; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8370.html http://www.clinicaltrials.gov/ct/search?term=NCT01440816 NCT01440816 This phase II trial studies how well giving interleukin-12 gene and in vivo electroporation-mediated plasmid DNA vaccine therapy works in treating patients with Merkel cell cancer. Placing the gene for interleukin-12 into Merkel cells may help the body build an effective defense to kill tumor cells. - Ages Eligible for Study: 18 Years and older - Genders Eligible for Study: Both - Patients must have biopsy-confirmed Merkel cell carcinoma - Patients must have at least one injectable lesion, defined as an easily palpable superficial lesion (cutaneous, subcutaneous or lymph nodal metastasis) that can be accurately localized, stabilized by palpation, and is superficial enough to enable intratumoral injection and electroporation; the injectable lesion must not be in close proximity to another tissue (e.g. nerve, bone) that could put patient safety at risk - Eastern Cooperative Oncology Group (ECOG) performance status score 0 to 2 - Life expectancy of greater than three months - Absolute neutrophil count > 1,000/uL - Platelet count > 50,000/uL - Creatinine =< 2.0 x upper limit of normal (ULN) - Bilirubin =< 2.0 x ULN - Prothrombin time (PT) and partial thromboplastin time (PTT) =< 1.5 x ULN - Patients must be willing, at the time of the entry to the study, to undergo the pre-treatment fine needle aspiration (FNA) plus biopsy (if indicated) AND the post-treatment FNA plus biopsy (or surgery) of at least one injected lesion (FNA is essential to determine the primary endpoint of the study); NOTE: The pre-treatment biopsy will be obtained from a superficial not-to-be-injected lesion; the post-treatment biopsy of an injected lesion will be obviated if definitive surgical resection is planned - The effects of this treatment approach on the developing human fetus are unknown; for this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately - Patients must have the ability to understand and the willingness to sign a written informed consent document - Both men and women, and members of all races and ethnic groups are eligible for this trial Other eligibility criteria may apply. - Patients who have had prior chemotherapy, investigational therapy or a major surgical procedure within 4 weeks or radiotherapy within 2 weeks prior to first day of treatment - Patients must not be receiving concurrently any other anti-cancer treatment (including topical agents such as imiquimod) or investigational agents, which could potentially interfere with the study treatment and/or study endpoints - Patients with active untreated brain metastases will be excluded - Pregnant or breast feeding women are excluded because effects of this treatment on the fetus or passage through milk are unknown - Patients with electronic pacemakers or defibrillators or those with a history of life threatening cardiac arrhythmia or uncontrolled seizure disorder are excluded - Use of any immunosuppressive treatments including corticosteroids, cyclosporine, mycophenolate mofetil et cetera, within 4 weeks prior to Day 1 of treatment will not be allowed; NOTE: Patients on topical or physiologic doses (for hormone-replacement therapy) of corticosteroids will be allowed - Patients, who are judged to be immunosuppressed due to uncontrolled human immunodeficiency virus (HIV) infection, severe uncontrolled diabetes, concurrent hematological malignancy, or other comorbidities, will be excluded - Uncontrolled intercurrent illness including, but not limited to, ongoing or active serious infection, symptomatic congestive heart failure, unstable angina pectoris, serious autoimmune conditions or psychiatric illness/social situations that would limit compliance with study requirements - Patients receiving concurrent therapeutic-dose anticoagulation will be excluded Other exclusion criteria may apply. 099d66713cff403e3d5c47af749d3ac2 8458 Bevacizumab in Treating Patients With Recurrent or Progressive Meningiomas II Marc Chamberlain, MD 7329 12; 16; 83; 126 Brain Cancer; Central Nervous System (CNS); Solid Tumors; Meningioma Fereshteh Assadian 206/288-6693 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8458.html http://www.clinicaltrials.gov/ct/search?term=NCT01125046 NCT01125046 RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. PURPOSE: This phase II trial is studying how well bevacizumab works in treating patients with recurrent or progression meningiomas. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Histologically proven recurrent or progressive intracranial meningioma; this includes benign, atypical, or malignant meningioma who may or may not have neurofibromatosis type 1 or 2; pathology can be from initial surgery; OR histologically proven intracranial hemangiopericytoma, hemangioblastoma (with or without metastatic disease), acoustic neuroma, or intracranial schwannoma - Unequivocal evidence for tumor progression by MRI (or CT scan if MRI is contraindicated); the scan must be performed within 14 days of registration - Steroid dosing- must be on stable dose for at least 5 days prior to baseline imaging (Steroids are not required at the time of baseline imaging) - Recent resection for recurrent tumor - patients will be eligible as long as they are greater than four weeks from surgery, have recovered from the effects of surgery, and have residual disease that can be evaluated; to best assess the extent of residual disease post-operatively, a CT/MRI should be done no later than 96 hours in the immediate post-operative period or at least 4 weeks post-operatively; if the 96 hour scan is more than 14 days before registration, it should be repeated - Prior radiation therapy - patients may have been treated with standard external beam radiation or radiosurgery in any combination; an interval of >= 8 weeks (56 days) must have elapsed from the completion of radiation therapy to study entry and there must be subsequent evidence of tumor progression - Patients with prior stereotactic radiosurgery must have confirmation of true progressive disease rather than radiation necrosis based on PET, MR spectroscopy or surgical documentation of disease - Prior therapy: there is no limitation on the number of prior surgeries, radiation therapy, radiosurgery treatments, or chemotherapy agents - Prior surgery: must be > 4 weeks from surgery - Prior radiation: must be 8 weeks from end of treatment - Prior chemotherapy: must be at least 4 weeks from cytotoxic therapy and 2 weeks from biologic therapies - All patients must sign an informed consent indicating that they are aware of the investigational nature of the study - Patients must sign an authorization for the release of their protected health information - Karnofsky performance status >= 60% - Absolute neutrophil count (ANC) >= 1,000/mm^3 - Platelets >= 100,000/mm^3 - Hemoglobin >= 8gm/dl - Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 x local laboratory upper limit of normal (ULN) - Serum alanine transaminase (ALT; serum glutamic pyruvic transaminase [SGPT]) =< 2.5 x local laboratory upper limit of normal (ULN) - Creatinine =< 2.0 mg/dl - PT, INR, and PTT =< 1.5 times institutional upper limits of normal - Total serum bilirubin =< 1.5 - Patients with a history of NF may have other stable CNS tumors, such as schwannoma, acoustic neuroma, or ependymoma, but ONLY if these lesions have been stable in size for the preceding 6 months - No history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix) unless in complete remission and off all therapy for the disease for a minimum of 5 years - Patients may not have a history of prior treatment with inhibitors of the VEGF pathway (eg: VEGF trap, cediranib, vatalanib, sunitinib, sorafenib, etc.) - No concurrent treatment on another clinical trial; supportive care trials or non-treatment trials, e.g. QOL, are allowed - No history of known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness or other active infection - Anticoagulation with therapeutic warfarin (INR <3) and low molecular weight heparin is allowed - Pregnancy or breast-feeding (Patients must be surgically sterile, postmenopausal, or agree to use effective contraception during the period of therapy; the definition of effective contraception will be based on the judgment of the principal investigator or a designated associate) - Male patients must be surgically sterile or agree to use effective contraception; women of childbearing potential must have a negative B-HCG pregnancy test documented within 14 days prior to registration - Patient must be able to comply with the study and follow-up procedures - Life expectancy greater than 12 weeks - Adequately controlled hypertension (defined as systolic blood pressure =< 150 mmHg and/or diastolic blood pressure =< 100 mmHg) - No history of hypertensive crisis or hypertensive encephalopathy - Patients must not have New York Heart Association (NYHA) Grade II or greater congestive heart failure - No history of myocardial infarction or unstable angina within 12 months prior to Day 1 of treatment - No history of stroke or transient ischemic attack - Patients must not have significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1 of treatment - No history of hemoptysis (>= 1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1 of treatment - No evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation) - No history of major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 of treatment or anticipation of need for major surgical procedure during the course of the study - No history of minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1 of treatment - No history of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1 of treatment - Patients must not have serious non-healing wound, active ulcer, or unhealed bone fracture - Urine protein:creatinine (UPC) ratio =< 1.0 at screening OR urine dipstick for proteinuria < 2 (patients discovered to have >= 2 proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate =< 1g of protein in 24 hours to be eligible) - No known hypersensitivity to any component of bevacizumab - Patients may not have a prior history of bowel perforation Other eligibility criteria may apply. Other exclusion criteria may apply. 2d4636816ec7629b0982a87e0a24407e 8596 Vaccine Therapy in Treating Patients With Stage III-IV Ovarian Cancer I Nora Disis, MD 7396 34; 65; 83; 125 Gynecological Cancer; Ovarian Cancer; Solid Tumors; Primary Peritoneal Cancer (PPC) Tumor Vaccine Group, Study Line 206/543-6620 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8596.html http://www.clinicaltrials.gov/ct/search?term=NCT01322802 NCT01322802 PRIMARY OBJECTIVES: -To determine the safety of an IGFBP-2 Th polyepitope plasmid based vaccine in patients with advanced stage or recurrent ovarian cancer. -To determine the immunogenicity of IGFBP-2 Th polyepitope plasmid based vaccine in patients with advanced stage or recurrent ovarian cancer. - Patients must be at least 18 years of age - Patients with advanced stage (III/IV) or recurrent ovarian cancer, who have been treated to complete remission with standard therapies including primary debulking surgery. - A CA-125 level within normal limits for the testing laboratory must be documented within 90 days prior to enrollment when the assessment of CA-125 is applicable - Patients must be at least 28 days post cytotoxic chemotherapy, and/or monoclonal antibody therapy, prior to enrollment - Patients must be at least 28 days post systemic steroids prior to enrollment - Patients must have Eastern Cooperative Oncology Group (ECOG) Performance Status Score of =< 2 - Patients must have recovered from major infections and/or surgical procedures, and in the opinion of the investigator, not have any significant active concurrent medical illnesses precluding protocol treatment - Estimated life expectancy of more than 6 months - White Blood Cell (WBC) >= 3000/mm3 - Hemoglobin (Hgb) >= 10 mg/dl - Serum creatinine =< 2.0 mg/dl or creatinine clearance > 60 ml/min - Total bilirubin =< 2.5 mg/dl - Aspartate aminotransferase (AST)/Serum glutamic oxaloacetic transaminase (SGOT) =< 3 times upper limit of normal (ULN) - Blood glucose < 1.5 ULN Other eligibility criteria may apply. - Patients with any of the following cardiac conditions: symptomatic restrictive cardiomyopathy; unstable angina within 4 months prior to enrollment; New York Heart Association functional class III-IV heart failure on active treatment; symptomatic pericardial effusion - Uncontrolled diabetes - Patients with any contraindication to receiving sargramostim (rhuGM-CSF) based products - Ovarian cancer of a low malignant potential phenotype - Patients with any clinically significant autoimmune disease uncontrolled with treatment - Patients who are currently receiving an anti-IGF-IR monoclonal antibody as part of their treatment regimen - Patients who are simultaneously enrolled in any other treatment study Other exclusion criteria may apply. c57ce63dfc7f34e74acd0247743a760e 8611 TLR8 Agonist VTX-2337 and Cetuximab in Treating Patients With Locally Advanced, Recurrent, or Metastatic Squamous Cell Cancer of Head and Neck I Laura Chow 7406 35; 42; 56; 76; 83 Head and Neck Cancer; Laryngeal Cancer; Mouth Cancer; Salivary Gland Cancer; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8611.html http://www.clinicaltrials.gov/ct/search?term=NCT01334177 NCT01334177 This phase I trial studies the side effects and best dose of TLR8 Agonist VTX-2337 when given together with cetuximab in treating patients with locally advanced, recurrent, or metastatic squamous cell cancer of the head and neck (SCCHN). Biological therapies, such as TLR8 Agonist VTX-2337 may stimulate the immune system in different ways and stop tumor cells from growing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving TLR8 Agonist VTX-2337 together with cetuximab may kill more tumor cells. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Patients with a histological or cytopathological confirmed diagnosis of squamous cell carcinoma of the head and neck region that is: - Locally advanced/recurrent and no longer amenable to local surgical or radiation therapy - and/or - Has evidence of metastatic disease - Patients may have been previously treated with systemic therapy but are otherwise deemed currently platinum-refractory, or would be deemed inappropriate or intolerant to platinum-based chemotherapy - Patients must have completed definitive chemotherapy and/or radiation therapy >= 3 months prior to study entry - Prior therapy with agents targeting/blocking the epidermal growth factor receptor (e.g. cetuximab and erlotinib) is allowable - Performance Status: Eastern Cooperative Oncology Group (ECOG) 0 - 2 - Expected life expectancy of at least 12 weeks, as assessed by the Investigator - Ability and willingness to comply with the study's visit and assessment schedule and to provide voluntary written informed consent - Absolute neutrophil count (ANC) >= 1,500 cells/µL - Platelet count >= 75,000 cells/µL - Hemoglobin >= 8.0 g/dL - Creatinine =< 2.0 mg/dL - Total bilirubin =< 2.0 x upper limit of normal (ULN) - Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]), serum glutamic pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2.5 x ULN - For patients with liver metastases, AST, ALT < 5x ULN is acceptable - Willingness to use a medically acceptable method of contraception throughout the study period and for 4 weeks after the final administration of VTX-2337 (all subjects) - For female subjects with reproductive potential: a negative serum pregnancy test Other eligibility criteria may apply. - Investigational therapy within 4 weeks of study entry - Chemotherapy therapy or palliative radiation therapy within the previous 2 weeks prior to dosing with cetuximab or VTX-2337; patients should have recovered from major toxicities of prior therapy (If deemed reversible, toxicities should return to baseline or =< grade 2 in severity) - Major surgery within the past 4 weeks prior to dosing with cetuximab or VTX-2337 - Concurrent symptomatic central nervous system (CNS) involvement, brain or leptomeningeal metastases; treated CNS involvement which has been stable > 28 days off systemic steroids may be included - Major active psychiatric disorders which would limit compliance - Treatment with oral or parenteral corticosteroids within 2 weeks prior to dosing with VTX-2337 or a requirement for systemic immunosuppressive therapy for any reason - Active autoimmune disease - Clinically significant cardiac disease (e.g., congestive heart failure, unstable or uncontrolled angina, myocardial infarction) within 6 months of dosing with VTX-2337 - Clinically significant ophthalmologic disease, defined as: - Current retinal vascular disorder, including active untreated diabetic retinopathy - and/or - Previous or current uveitis - Infection requiring parenteral antibiotic therapy or causing fever (temp > 100.5 degrees Fahrenheit [F] or 38.1 degrees Celsius [C]) within 1 week prior to dosing with VTX-2337 - Pregnant or breast-feeding females - Uncontrolled inter-current illness, pre-planned surgery or procedure requiring hospitalization during the study period, or any other condition or circumstance that could interfere with adherence to the study's procedures or requirements, or otherwise compromise the study's objectives - Second primary malignancy that is clinically detectable (not including in situ carcinoma of the cervix, non-melanoma skin cancer or low-grade [Gleason score =< 6] localized prostate cancer) and demonstrating active progression at the time of consideration for study enrollment - Known prior severe allergic/hypersensitivity to cetuximab or any of the components of the study treatment - Known prior severe (>= Grade 3) rash and / or diarrhea toxicities to cetuximab Other exclusion criteria may apply. 73d5f8e9c262a78d07a40257d3961702 8631 Vaccine Therapy in Combination With Ampligen® and/or Sargramostim in Patients With Stage II-IV HER2-Positive Breast Cancer I/II Lupe Salazar, MD 7425 13; 83 Breast Cancer; Solid Tumors Tumor Vaccine Group, Study Line 206/543-6620 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8631.html http://www.clinicaltrials.gov/ct/search?term=NCT01355393 NCT01355393 PRIMARY OBJECTIVES: - To determine the Ampligen® “maximum biologic dose” (MBD) defined as the dose that results in the highest incidence and magnitude of HER2 immune response and the lowest incidence of toxicity when given with a HER2 vaccine. (Stage I of study) - To determine if the Ampligen® MBD (defined in Stage I) when combined with GM-CSF as an adjuvant strategy with a HER2 vaccine increases the incidence and magnitude of HER2 immune response compared to the standard GM-CSF adjuvant strategy. (Stage II of study) Ages Eligible for Study: Patients must be at least 18 years of age - Patients with stage II, or III HER2+ breast cancer who have completed definitive standard treatment and are in complete remission - or - - Patients with stage IV HER2+ breast cancer treated to: No evidence of disease, or Stable bone only disease after definitive therapy - Patients must have demonstrated HER2 positive disease, by one of the following methods: Immunohistochemical (IHC) staining of 1+, 2+ or 3+ for the HER2 protein, or Amplification of the HER2 gene on fluorescence in situ hybridization (FISH) - Patients cannot be receiving any concurrent immunomodulators (such as trastuzumab/herceptin) during vaccine therapy - Patients must be at least 14 days post cytotoxic chemotherapy prior to enrollment - Patients must be at least 14 days post systemic steroids prior to enrollment - Patients on bisphosphonates or continued hormone therapy are eligible - Men and women of reproductive ability must agree to contraceptive use during the entire study period - Patients must have Zubrod Performance Status Score of =< 2 - Patients must have recovered from major infections and/or surgical procedures, and in the opinion of the investigator, not have any significant active concurrent medical illnesses precluding protocol treatment - White blood cell count (WBC) >= 3000/mm^3 - Hemoglobin (Hgb) >= 10 mg/dl - Serum creatinine =< 2.0 mg/dl or creatinine clearance > 60 ml/min - Total bilirubin =< 1.5 mg/dl - Serum glutamic oxaloacetic transaminase (SGOT) =< 2.5 times the upper limit of normal - Patients on trastuzumab monotherapy must have adequate cardiac function as demonstrated by normal ejection fractions (EF) on multi gated acquisition scan (MUGA) scan or echocardiogram performed within the last 3 months of eligibility sign off Other eligibility criteria may apply. - Patients with any of the following cardiac conditions: restrictive cardiomyopathy; unstable angina within 6 months prior to enrollment; New York Heart Association functional class III-IV heart failure; symptomatic pericardial effusion - Patients with any contraindication to receiving rhuGM-CSF based products - Patients with any clinically significant autoimmune disease requiring active treatment - Patients receiving any concurrent immunomodulators (such as Trastuzumab/herceptin) during vaccine therapy - Patients who are pregnant or breast-feeding - Patients who are simultaneously enrolled in any other treatment study - Patients who have received a previous HER2 breast cancer vaccine Other exclusion criteria may apply. 5ac8cbc33e21c03bc64b55d50626441a 8809 Pazopanib Hydrochloride Followed By Chemotherapy and Surgery in Treating Patients With Soft Tissue Sarcoma Pilot Robin Jones 7487 77; 83 Sarcoma; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8809.html http://www.clinicaltrials.gov/ct/search?term=NCT01446809 NCT01446809 This randomized pilot clinical trial studies pazopanib hydrochloride followed by chemotherapy and surgery in treating patients with soft tissue sarcoma. Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes that are needed for cell growth and may also stop the growth of soft tissue sarcoma by blocking blood flow to the tumor. Giving pazopanib hydrochloride and chemotherapy before surgery may make the tumor smaller and reduce the amount of tissue that needs to be removed. - Ages Eligible for Study: 18 Years and older - Genders Eligible for Study: Both - Histologically or cytologically confirmed soft-tissue sarcoma, excluding alveolar and embryonal rhabdomyosarcoma, well and dedifferentiated adipocytic sarcomas, Ewing's, osteosarcoma, or gastrointestinal stromal tumor; American Joint Committee on Cancer (AJCC) (6th Edition) Stage III or T2a Stage II or Stage IV treatment naive patients planned for resection of the primary tumor, with resectable metastatic disease - Measurable disease greater than 5 centimeters in greatest dimension; measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter for non-nodal lesions and short axis for nodal lesions to be recorded) by chest x-ray, computed tomography (CT) scan, magnetic resonance imaging (MRI) or with calipers by clinical exam; all tumor measurements must be recorded in millimeters (or decimal fractions of centimeters) - Intermediate or high grade lesions: 2 or 3 on a scale of 1-3 or grades 2 to 4 on a scale of 1-4 - Sarcoma located on upper (includes shoulder) or lower (includes hip) extremities or on the body wall - Life expectancy of greater than 6 months - Eastern Cooperative Oncology Group (ECOG) performance status =< 1 - Karnofsky >= 80% - No prior chemotherapy, radiotherapy, or antiangiogenic therapy - Absolute neutrophil count (ANC) >= 1500 /uL - Hemoglobin (Hgb) >= 9.0 g/dL - Platelets >= 100,000/uL - Creatinine =< 1.5 x upper limit of normal (ULN) - Bilirubin =< 1.5 mg/dL - Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 1.5 x ULN - Prothrombin time (PT)/international normalized ratio(INR)/partial thromboplastin time (PTT) within 1.2 X the ULN unless a subject is receiving Coumadin and has stable INR which is in range for the desired level of anticoagulation - Left ventricular ejection fraction (LVEF) >= 50% - Blood pressure (BP) no greater than 140 mmHg (systolic) and 90 mmHg (diastolic) for eligibility; initiation or adjustment of BP medication is permitted prior to study entry provided that the average of three BP readings on baseline assessment prior to enrollment is less than 140/90 mmHg - Eligibility of subjects receiving any medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of pazopanib will be determined following review of their cases by the Principal Investigator - Women of child-bearing potential and men must agree to use adequate contraception - A female is eligible to enter and participate in this study if she is of non-childbearing potential (i.e., physiologically incapable of becoming pregnant) or if she is of childbearing potential - Ability to understand and the willingness to sign a written informed consent document Other eligibility criteria may apply. - Subjects with known brain metastases and/or unresectable sarcoma - Uncontrolled intercurrent illness including, active serious infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac ventricular arrhythmia requiring anti-arrhythmic therapy, or psychiatric illness/social situations that would limit compliance with study - Pregnant or lactating women - Subjects with a currently active second malignancy other than non-melanoma skin cancers - Subjects receiving other investigational agents - Subjects with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to pazopanib or other agents used in the study - Subjects who have both bilirubin > ULN and AST/ALT > ULN - Subjects with a urine protein/creatinine ratio greater than 1 - Subjects with a baseline QTc of equal to or greater than 480 msecs or other significant electrocardiogram (ECG) abnormalities - Certain medications that act through the cytochrome P450 (CYP450) system are specifically prohibited in subjects receiving pazopanib and others should be avoided or administered with extreme caution and require principal investigator (PI) approval -1) Strong inhibitors of CYP3A4 such as ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole may increase pazopanib concentrations and are prohibited; grapefruit juice is also an inhibitor of CYP450 and should not be taken with pazopanib - 2) Strong inducers of CYP3A4, such as rifampin, may decrease pazopanib concentrations, are prohibited - 3) Medications which have narrow therapeutic windows and are substrates of CYP3A4, CYP2D6, or CYP2C8 should be avoided and, if necessary, administered with caution - 4) Pazopanib, 800 mg once daily, has no effect on CYP2C9, CYP1A2, or CYP2C19 in vivo but does in vitro; therefore, therapeutic doses of warfarin, a substrate of CYP2C9, and omeprazole, a substrate of CYP2C19 are permitted; caffeine, a substrate of CYP1A2, is also permitted - Certain medications that are associated with a risk for QTc prolongation and/or Torsades de Pointes, although not prohibited, should be avoided or replaced with medications that do not carry these risks, if possible - Subjects who require heparin other than low-molecular weight heparin - Subjects with any condition that may impair the ability to swallow or absorb oral medications/investigational product including: - 1) Any lesion, whether induced by tumor, radiation or other conditions, which makes it difficult to swallow capsules or pills - 2) Prior surgical procedures affecting absorption including, but not limited to major resection of stomach or small bowel - 3) Active peptic ulcer disease, not on a proton pump inhibitor - 4) Malabsorption syndrome - Subjects with any condition that may increase the risk of gastrointestinal bleeding or gastrointestinal perforation, including: - 1) Active peptic ulcer disease, not on a proton pump inhibitor - 2) Known intraluminal metastatic lesions - 3) Inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease) or - 4) Other gastrointestinal conditions which increase the risk of perforation - 5) History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days prior to beginning study treatment - Subjects with any of the following cardiovascular conditions within the past 6 months: - 1) Cerebrovascular accident (CVA) or transient ischemic attack (TIA) - 2) Cardiac arrhythmia - 3) Admission for unstable angina - 4) Cardiac angioplasty or stenting - 5) Coronary artery bypass graft surgery - 6) Pulmonary embolism, untreated deep venous thrombosis (DVT) or DVT which has been treated with therapeutic anticoagulation for less than 6 weeks - 7) Arterial thrombosis - 8) Symptomatic peripheral vascular disease - 9) Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system; a subject who has a history of Class II heart failure and is asymptomatic on treatment may be considered eligible - History of hemoptysis in excess of 2.5 mL (1/2 teaspoon ) within 8 weeks prior to first dose of study drug - History of serious or non-healing wound, ulcer, or bone fracture - Human immunodeficiency virus (HIV)-positive subjects on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with pazopanib Other exclusion criteria may apply. 715500673d2aef5785fdb861c8cee252 8783 Radiation Therapy, Cisplatin, and Etoposide in Treating Patients With Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery I Shilpen Patel, MD 7506 46; 83 Lung Cancer; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8783.html http://www.clinicaltrials.gov/ct/search?term=NCT01411098 NCT01411098 Purpose This phase I trial studies the side effects and best dose of radiation therapy when given together with cisplatin and etoposide in treating patients with non-small cell lung cancer that cannot be removed by surgery. Radiation therapy uses high energy x rays to kill tumor cells. Drugs used in chemotherapy, such as cisplatin and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Drugs, such as cisplatin, may make tumor cells more sensitive to radiation therapy. Giving radiation therapy together with cisplatin and etoposide may kill more tumor cells Genders Eligible for Study: Both - Patients with confirmed unresectable Stage IIB or Stage III non-small cell lung cancer of any histologic-subtype appropriate for definitive concurrent chemotherapy and radiation as determined by multi-disciplinary assessment; all detectable tumor should be encompassable by radiation therapy fields, including both the primary tumor and the involved regional lymph nodes - Granulocytes >= 1500/ul - Platelets >= 100,000/ul - Bilirubin < 1.5 mg/dl - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) < 2 upper limit of normal (ULN) - Creatinine clearance must be > 60ml/min - Eastern Cooperative Oncology Group (ECOG) 0 to 1 - Weight loss =< 5% in the previous six months unless weight loss is intentional (per judgment of study medical doctor [MD]) - Forced expiratory volume in one second (FEV1) must be >= 1.0 L - Patients must sign a study-specific informed consent form prior to study entry - Patients must have measurable disease on the 3D planning computed tomography (CT) - Patient must have a completed 3D plan and the attending physician must have reviewed and approved the dose volume histograms as follows: total lung volume percentage receiving at least 20 Gy (V20) =< 35%, and mean lung dose =< 20 Gy Other eligibility criteria may apply. - Mixed histology or undifferentiated small cell carcinoma, any stage - Concurrent malignancy except non-melanomatous skin cancer or prior cancer if disease-free for one year or more - Patients with malignant pleural effusions or significant pericardial effusions - Pregnant or lactating females - Severe neuropathy greater than or equal to grade 2 - Severe sensorineural hearing loss greater or equal to grade 2 - No clinically significant history of cardiac disease, (i.e. uncontrolled hypertension, unstable angina, congestive heart failure, myocardial infarction within the past year, or cardiac ventricular arrhythmias requiring medication) - Any significant or severe medical conditions or psychiatric or social conditions that would preclude adherence to the protocol or compliance with study treatments Other exclusion criteria may apply. aa22dfacc6d6784168629574bcb13987 9008 I-SPY 2 TRIAL: Neoadjuvant and Personalized Adaptive Novel Agents to Treat Breast Cancer II Larissa Korde 7518 13; 83 Breast Cancer; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9008.html http://www.clinicaltrials.gov/ct/search?term=NCT01042379 NCT01042379 The purpose of this study is to further advance the ability to practice personalized medicine by learning which new drug agents are most effective with which types of breast cancer tumors and by learning more about which early indicators of response (tumor analysis prior to surgery via magnetic resonance imaging (MRI) images along with tissue and blood samples) are predictors of treatment success. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Female - Histologically confirmed invasive cancer of the breast - Clinically or radiologically measureable disease in the breast after diagnostic biopsy, defined as longest diameter greater than or equal to 25 mm (2.5cm) - No prior cytotoxic regimens are allowed for this malignancy. Patients may not have had prior chemotherapy or prior radiation therapy to the ipsilateral breast for this malignancy. Prior bis-phosphonate therapy is allowed - Age =18 years - ECOG performance status 0-1 - Willing to undergo core biopsy of the primary breast lesion to assess baseline biomarkers - Non-pregnant and non-lactating - No ferromagnetic prostheses. Patients who have metallic surgical implants that are not compatible with an MRI machine are not eligible. - Ability to understand and willingness to sign a written informed consent (I-SPY TRIAL Screening Consent) - Eligible tumors must meet one of the following criteria: Stage II or III, or T4, any N, M0, including clinical or pathologic inflammatory cancer or Regional Stage IV, where supraclavicular lymph nodes are the only sites metastasis - Any tumor ER/PgR status, any HER-2/neu status as measured by local hospital pathology laboratory and meets any tumor assay profile described in protocol section 4.1.2F - Normal organ and marrow function: Leukocytes = 3000/µL, Absolute neutrophil count = 1500/µL, Platelets = 100,000/µL, Total bilirubin within normal institutional limits, unless patient has Gilbert's disease, for which bilirubin must be = 2.0 x ULN, AST(SGOT)/ALT (SGPT) = 1.5 x institutional ULN, creatinine < 1.5 x institutional ULN - No uncontrolled or severe cardiac disease. Baseline ejection fraction (by nuclear imaging or echocardiography) must by = 50% - No clinical or imaging evidence of distant metastases by PA and Lateral CXR, Radionuclide Bone scan, and LFTs including total bilirubin, ALT, AST, and alkaline phosphatase - Tumor assay profile must include on of the following: MammaPrint High, any ER status, any HER2 status, or MammaPrint Low, ER negative (<5%), any HER2 status, or MammaPrint Low, ER positive, HER2/neu positive by any one of the three methods used (IHC, FISH, TargetPrint™) - Ability to understand and willingness to sign a written informed consent document (I-SPY 2 TRIAL Consent #2) Other eligibility criteria may apply. - Use of any other investigational agents within 30 days of starting study treatment - History of allergic reactions attributed to compounds of similar chemical or biologic composition to the study agent or accompanying supportive medications. - Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Other exclusion criteria may apply. 220b2e53bc304705dd9b68d725be7f01 8768 Iodine I 131 and Pazopanib Hydrochloride in Treating Patients With Recurrent and/or Metastatic Thyroid Cancer Previously Treated With Iodine I 131 That Cannot Be Removed By Surgery I Laura Chow 7529 35; 83; 89 Head and Neck Cancer; Solid Tumors; Thyroid Cancer Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8768.html http://www.clinicaltrials.gov/ct/search?term=NCT01413113 NCT01413113 This phase I trial is studying the side effects and best dose of iodine I 131 when given together with pazopanib hydrochloride in treating patients with recurrent and/or metastatic thyroid cancer previously treated with iodine I 131 that cannot be removed by surgery. Radioactive drugs, such as iodine I 131, may carry radiation directly to cancer cells and not harm normal cells. Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving iodine I 131 together with pazopanib hydrochloride may be an effective treatment for thyroid cancer. - Subjects must provide written informed consent prior to performance of study-specific procedures or assessments, and must be willing to comply with treatment and follow up; procedures conducted as part of the subject's routine clinical management (e.g., blood count, imaging study) and obtained prior to signing of informed consent may be utilized for screening or baseline purposes provided these procedures are conducted as specified in the protocol - Histologically confirmed diagnosis of well-differentiated thyroid carcinoma (WDTC), including papillary and follicular subtypes, and documented recurrent and/or metastatic disease; patients must have unresectable disease: patients must not be amenable to surgery but prior thyroidectomy is allowed - Patient must have demonstrated evidence of disease progression by RECIST criteria using site assessment of computed tomography (CT)/magnetic resonance imaging (MRI) scans within 12 months (+1 month to allow for variances in patient scanning intervals) prior to study entry or by > 50% increase in suppressed thyroglobulin levels during this time period - Patients with WDTC must be relatively 131I refractory/resistant as defined by at least one of the following: - a) One or more measurable lesions with low or absent 131I uptake on the most recent pre-study radioiodine scans, based on a visual review of scans or RAI scan reports - b) One or more measurable lesions with disease progression by RECIST within 12 months (+ 1 month to allow for variances in patient scanning intervals) of 131I therapy despite 131I uptake on RAI scan, based on site assessment of CT/MRI scans or by > 50% increase in suppressed thyroglobulin levels during this time period - c) Evidence of at least one site of known disease with preserved 131I uptake above background levels on a diagnostic post-therapy 131I scan prior to study entry - d) Patients with WDTC must be receiving thyroxine suppression therapy and thyroid-stimulating hormone (TSH) should not be elevated (TSH should be =< 5.50 mcu/mL) - Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 - Absolute neutrophil count (ANC) >= 1.5 X 10^9/L - Hemoglobin >= 9 g/dL (5.6 mmol/L) - Platelets >= 90 X 10^9/L - International normalized ratio (INR) =< 1.2 X upper limit of normal (ULN); subjects receiving anticoagulant therapy are eligible if their INR is stable and within the recommended range for the desired level of anticoagulation - Activated partial thromboplastin time (aPTT) =<1.2 X ULN - Total bilirubin =< 1.5 X ULN - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 X ULN, and < 5 X ULN in the presence of liver metastases; concomitant elevations in bilirubin and AST/ALT above 1.5 x ULN are not permitted - Serum creatinine =< 2.0 mg/dL or, if serum creatinine > 2.0 mg/dL, calculate creatinine clearance (CLCR) >= 30 mL/min - Urine protein to creatinine ratio (UPC) < 1 or, 24-hour urine protein < 1 g; if UPC >= 1, then a 24-hour urine protein must be assessed; subjects must have a 24-hour urine protein value < 1 g to be eligible; use of urine dipstick for renal function assessment is not acceptable - Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who has had: - a) A hysterectomy - b) A bilateral oophorectomy (ovariectomy); a bilateral tubal ligation - c) Is post-menopausal (subjects not using hormone replacement therapy [HRT] must have experienced total cessation of menses for >= 1 year and be greater than 45 years in age, OR, in questionable cases, have a follicle stimulating hormone [FSH] value > 40 mIU/mL and an estradiol value < 40pg/mL [< 140 pmol/L]; subjects using HRT must have experienced total cessation of menses for >= 1 year and be greater than 45 years of age OR have had documented evidence of menopause based on FSH and estradiol concentrations prior to initiation of HRT) - Childbearing potential, including any female who has had a negative serum pregnancy test within 2 weeks prior to the first dose of study treatment, preferably as close to the first dose as possible, and agrees to use adequate contraception for at least 2 weeks following the last dose of the investigational product - GlaxoSmithKline (GSK) acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follow: - a) Complete abstinence from sexual intercourse for 14 days before exposure to investigational product, through the dosing period, and for at least 21 days after the last dose of investigational product - b) Oral contraceptive, either combined or progestogen alone - c) Injectable progestogen - d) Implants of levonorgestrel - e) Estrogenic vaginal ring - f) Percutaneous contraceptive patches - g Intrauterine device (IUD) or intrauterine system (IUS) with a documented failure rate of less than 1% per year - h) Male partner sterilization (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study, and this male is the sole partner for that subject - I) Double barrier method: condom and an occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal agent (foam/gel/film/cream/suppository) - Female subjects who are lactating should discontinue nursing prior to the first dose of study drug and should refrain from nursing throughout the treatment period and for 14 days following the last dose of study drug Other eligibility criteria may apply. - Patients with medullary thyroid cancer, thyroid lymphoma or anaplastic thyroid cancer are excluded - Resolution of all acute toxic effects of prior systemic therapy (including iodine therapy or systemic therapy), radiotherapy or surgical procedure to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 grade =< 1 - Patients with cumulative iodine I 131 exposure in excess of 1000 mCi - Second primary malignancy that is of clinical significance, clinical detectable and/or progressing at the time of consideration for study enrollment - History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids for 28 days prior to first dose of study drug; screening with CNS imaging studies (CT or MRI) is required only if clinically indicated or if the subject has a history of CNS metastases; clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to: - a) Active peptic ulcer disease - b) Known intraluminal metastatic lesion/s with risk of bleeding - c) Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), or other gastrointestinal conditions with increased risk of perforation - d) History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment - Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to: - a) Malabsorption syndrome - b) Major resection of the stomach or small bowel - Presence of uncontrolled infection - Corrected QT interval (QTc) > 480 msecs using Bazett's formula - History of any one or more of the following cardiovascular conditions within the past 6 months: - a) Cardiac angioplasty or stenting - b) Myocardial infarction - c) Unstable angina - d) Coronary artery bypass graft surgery - e) Symptomatic peripheral vascular disease - f) Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA) - Poorly controlled hypertension [defined as systolic blood pressure (SBP) of >= 140 mmHg or diastolic blood pressure (DBP) of >= 90mmHg] --- Note: initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry - History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months; subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible - Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major) - Evidence of active bleeding or bleeding diathesis - Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage; Note: lesions infiltrating major pulmonary vessels (contiguous tumor and vessels) are excluded; however, the presence of a tumor that is touching, but not infiltrating (abutting) the vessels is acceptable (CT with contrast is strongly recommended to evaluate such lesions) - Recent Hemoptysis in excess of 15 ml of bright red blood in the 8 weeks prior to study entry - Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures - Unable or unwilling to discontinue use of prohibited medications for at least 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of study drug and for the duration of the study - Treatment with any of the following anti-cancer therapies: - a) Radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of pazopanib OR - b) Chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of pazopanib Other exclusion criteria may apply. 6b12420d5a50026dd0435368fa825bf4 9075 Phenelzine Sulfate and Docetaxel for Patients With Prostate Cancer With Progressive Disease After First-Line Therapy With Docetaxel II Evan Yu, MD 7563 71; 83 Prostate Cancer; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9075.html http://www.clinicaltrials.gov/ct/search?term=NCT01253642 NCT01253642 Phenelzine sulfate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Phenelzine sulfate may also help docetaxel work better by making tumor cells more sensitive to the drug. Giving phenelzine sulfate together with docetaxel may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving phenelzine sulfate together with docetaxel works in treating patients with prostate cancer with progressive disease after first-line therapy with docetaxel. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Male - Histological or cytological diagnosis of adenocarcinoma of the prostate - Radiographic evidence of regional or distant metastases with suspected tumor in an area that is safe to biopsy - Willingness to undergo a baseline tumor biopsy - Evidence of castration resistant prostate cancer (CRPC) indicated by history of progression despite standard hormonal therapy (by PSA and/or imaging studies) - Prior therapy with at least four cycles of docetaxel with at least one PSA measurement during docetaxel therapy that was lower than the pre-docetaxel baseline. Combination therapy that includes docetaxel and non-cytoxic agents (biologic agents) is allowable; prior treatment with weekly docetaxel is not allowable - Evidence of early progression during (while on therapy or within 45 days of the last dose administered) docetaxel therapy defined as: - Increasing serum PSA level: Three increasing measurements obtained after exposure to first-line docetaxel treatment are required; if the third PSA value is less than the second, an additional fourth test to confirm a rising PSA is acceptable - AND/OR progressive measurable disease: at least a 20% increase in the sum of the longest diameters of measurable lesions over the smallest sum observed -or- the appearance of one or more new lesions as assessed by CT scan after exposure to first-line docetaxel treatment; measurable lesions include nodal lesions >= 20 mm in diameter or visceral/soft-tissue lesions >= 10 mm in diameter - AND/OR bone Scan Progression: appearance of 2 or more new lesions on bone scan after exposure to first-line docetaxel treatment - For patients who have been on anti-androgen therapy and had evidence of response to the addition of an anti-androgen (i.e. PSA reduction), patients must have discontinued anti-androgen therapy for at least six weeks (4 weeks for flutamide) without current evidence of an anti-androgen withdrawal response - Evidence of MAOA expression (2 or higher) in metastasis biopsy specimen - Serum testosterone levels < 50 ng/dL (unless surgically castrate); patients must continue androgen deprivation with an LHRH agonist if they have not undergone orchiectomy - ECOG performance status =< 2 - At least 15 days has passed since receiving the last dose of docetaxel at the time of initiation of study drug - Has recovered from all therapy-related toxicity to =< grade 2 (except alopecia, anemia and any signs or symptoms of androgen deprivation therapy) - Absolute neutrophil count >= 1500/uL - Platelets >= 100,000 - Bilirubin =< 1.5 times ULN (if total bilirubin elevated, but direct is WNL, patient is eligible) - ALT =< 2.5 times ULN - PSA > 2 ng/mL - Life expectancy > 3 months - Signed informed consent - For patients who meet all of the above criteria, but have been off docetaxel therapy for more than 6 weeks, current evidence of progression is also required Other eligibility criteria may apply. - Received any other cytotoxic chemotherapy as a second-line treatment after first-line docetaxel-based therapy - Significant peripheral neuropathy defined as grade 2 or higher - A second active malignancy except adequately treated non-melanoma skin cancer or other non-invasive or in situ neoplasm - Significant active concurrent medical illness or infection precluding protocol treatment or survival - Current uncontrolled hyperthyroidism - Pheochromocytoma - Carcinoid Syndrome - Known or suspected brain metastases - Treatment with radiotherapy within the past 4 weeks or radiopharmaceutical therapy (strontium, samarium) within the past 8 weeks - Concurrent therapy with a Selective Serotonin Reuptake Inhibitor (SSRI), tricyclic antidepressant, or Monoamine Oxidase Inhibitor (MAOi); clinical judgment should be used in a decision to discontinue antidepressants; a minimum of a 1 week washout period is required for any tricyclic or related antidepressant, or any SSRI (2 weeks for paroxetine or sertraline, 5 weeks for fluoxetine); minimum 2 week washout for any MAOi - Concurrent therapy: Excluded Concomitant medications: Sympathomimetic drugs or related compounds: Amphetamine, Dextroamphetamine, Benzphetamine, Dexmethylphenidate, Methamphetamine, phentermine, cocaine, methylphenidate, dopamine, epinephrine, norepinephrine, methyldopa, L-dopa (levodopa), L-tryptophan, L-tyrosine, Phenylalanine, Ephedrine, Isometheptene, Levonordefrin, Midodrine, meperidine (e.g., Demerol); other Monoamine oxidase (MAO) inhibitors: isocarboxazid (e.g., Marplan), procarbazine (e.g., Matulane), selegiline (e.g., Eldepryl), tranylcypromine (e.g., Parnate), pargyline hydrochloride, pargyline hydrochloride and methylclothiazide, furazolidone, rasagiline, buspirone HCL; Serotoninergic Drugs: fluvoxamine (e.g., Luvox), fluoxetine (e.g., Prozac), paroxetine (e.g., Paxil), sertraline (e.g., Zoloft), dexfenfluramine, citoprolam, venlafaxine, desvenlafaxine, duloxetine, escitalopram, milnacipran, Atomoxetine - Barbiturates, such as: Amobarbital, Butalbital, Pentobarbital, Phenobarbital, Secobarbital; Cough, Cold and Allergy products, such as: Dextromethorphan, Naphazoline, Oxymetazoline, Phenylephrine, Propylhexedrine, Pseudoephedrine; Tryptophan, Disulfiram, Entacapone, Reserpine, Sibutramine, Tolcapone, Bupropion HCL, guanethidine, serotonin receptor agonists (e.g. sumatriptan); Dibenzazepine Derivative Drugs: , nortriptyline hydrochloride, amitriptyline hydrochloride, perphenazine and amitriptyline hydrochloride, clomipramine hydrochloride, desipramine hydrochloride, imipramine hydrochloride, doxepin, carbamazepine, cyclobenzaprine HCl, amoxapine, maprotiline HCl, trimipramine maleate, protriptyline HCl, mirtazapine - Other chemotherapeutic agents or biological response modifiers will be prohibited for the duration of the study - All herbal supplements will be prohibited - The following foods and beverages must be avoided: Meat and Fish: Pickled herring, Liver, Dry sausage (including Genoa salami, hard salami, pepperoni, and Lebanon bologna); Vegetables: Broad bean pods (fava bean pods), Sauerkraut; Dairy Products: Cheese (particularly aged cheeses, cottage cheese and cream cheese are allowed), Yogurt; Beverages: Beer and wine, Alcohol-free and reduced-alcohol beer and wine products; Miscellaneous: Yeast extract (including brewer's yeast in large quantities), Meat extract, Excessive amounts of chocolate and caffeine - Systemic steroids other than as premedication will not be allowed on the study Other exclusion criteria may apply. 9efc672b5bc2e841f0f91b544746459b 8982 Multi-center Study of Myeloablative Allo Stem Cell Transplant for Non-remission AML Using CloBu4 Regimen II Pamela Becker, MD, PhD 7617 36; 43; 61 Hematologic Malignancies; Leukemia; Myelodysplastic and Myeloproliferative Syndromes (MDS and MPD) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8982.html http://www.clinicaltrials.gov/ct/search?term=NCT01457885 NCT01457885 Although transplant results for AML in complete remission (CR) at the time of transplant have improved, transplant results for non-remission AML have been quite poor. Most multi-center studies have focused on standard risk AML patients and not many studies have been done in this population of patients with non-remission AML. There are a large number of older patients with non-remission AML because the complete remission rate with induction chemotherapy decreases with age. Such older patients do not tolerate conventional full intensity conditioning regimens. Thus, an effective and tolerable conditioning regimen for non-remission AML is a great unmet need for current transplant practice. From the investigators earlier study, it is suggested that replacing Fludarabine of standard FluBu4 regimen by Clofarabine (a related drug with much more potent anti-leukemia effect) in the transplant conditioning regimen may potentiate the anti-tumor activity of the conditioning regimen without adding significant toxicity, a goal of new conditioning regimen development. The investigators expect to enroll a total of 75 patients from about fifteen sites. The investigators main objective is to confirm both the safety and efficacy as measured by one-year overall survival, of the CloBu4 combination as full intensity conditioning for non-remission acute myelogenous leukemia. Ages Eligible for Study: 2 Years to 65 Years Genders Eligible for Study: Both Inclusion Criteria: - AML not in remission at the time of transplant - "Not in remission" is defined as "greater than 5.0% bone marrow blasts by aspirate morphology," as determined by a bone marrow aspirate obtained within 2 weeks of study registration. - For primary induction failure patients: Patients must have failed at least 2 induction regimens. - For patients with relapsed disease: Patients who relapse more than 6 months after preceding remission must fail at least one reinduction regimen to be eligible. For patients in whom the preceding remission is equal to or shorter than 6 months duration, no re-induction regimen is required to qualify for this protocol. - If the pre-transplant bone marrow aspirate and biopsy are hypoplastic (less than 10% cellularity), and blast percentages cannot be determined, the patient is eligible if the preceding bone marrow met the above criteria. - Patients with peripheral circulating blasts or patients with extramedullary leukemia are eligible if bone marrow aspirate and biopsy meets the above criteria. Age and Organ Function Criteria - Age: 2 to 65 years in age. - Cardiac: LVEF = 40% by MUGA (Multi Gated Acquisition) scan or echocardiogram. - Pulmonary: FEV1 and FVC capacity) = 40% predicted, DLCO (corrected for hemoglobin) = 40% of predicted. - Children who are unable to cooperate for pulmonary function tests (PFTs), must have no evidence of dyspnea at rest, no exercise intolerance, and not require supplemental oxygen therapy. - Renal: Age equal to or older than 12: The estimated creatinine clearance (CrCl) must be equal or greater than 60 mL/min/1.73 m2 as calculated by the Cockcroft-Gault Formula. Age younger than 12: Either estimated or measured CrCl should be greater than 90 ml/min/1.73m2. For estimation, Schwartz formula will be used. - Hepatic: Serum bilirubin = 1.5 x upper limit of normal (ULN); (AST)/ ALT = 2.5 x ULN; Alkaline phosphatase = 2.5 x ULN - Performance status: Karnofsky = 70%., or Lansky=70% Consent: All patients must sign informed consent Other eligibility criteria may apply. - Active life-threatening cancer requiring treatment other than AML - Non-compliant to medications. - No appropriate caregivers identified. - HIV1 (Human Immunodeficiency Virus-1) or HIV2 positive - Active life-threatening cancer requiring treatment other than AML - Uncontrolled medical or psychiatric disorders. - Uncontrolled infections, defined as positive blood cultures within 72 hours of study entry, or evidence of progressive infection - Active central nervous system (CNS) leukemia - Preceding allogeneic HSCT - Receiving intensive chemotherapy within 21 days of registration. - Patients with preceding primary myelofibrosis - Peripheral blasts > 10,000/µL at the time of registration Other exclusion criteria may apply. 92caae86b8854a186f5ceed48e93e518 8975 Abiraterone Acetate in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer II Robert Montgomery, MD 7639 71; 83 Prostate Cancer; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8975.html http://www.clinicaltrials.gov/ct/search?term=NCT01503229 NCT01503229 This phase II trial studies how well giving abiraterone acetate works in treating patients with metastatic hormone-resistant prostate cancer. Abiraterone acetate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Male - Have signed an informed consent document indicating that the subjects understands the purpose of and procedures required for the study and are willing to participate in the study - Written authorization for use and release of health and research study information has been obtained - Be willing/able to adhere to the prohibitions and restrictions specified in this protocol - Able to swallow the study drug whole as a tablet - Willing to take abiraterone acetate on an empty stomach; no food should be consumed at least two hours before and for at least one hour after the dose of abiraterone acetate is taken - Patients who have partners of childbearing potential must be willing to use a method of birth control with adequate barrier protection as determined to be acceptable by the principal investigator and sponsor during the study and for 1 week after last dose of abiraterone acetate - Histologically proven adenocarcinoma of the prostate - Eastern Cooperative Oncology Group (ECOG) performance status =< 2 - Metastatic castration resistant prostate cancer as defined by serum testosterone < 50 ng/ml and one of the following: -- i) Prostate specific antigen (PSA) level of at least 2 ng/ml that has risen on at least 2 successive occasions at least 1 week apart -- ii) Evaluable disease progression by modified RECIST (Response Evaluation Criteria in Solid Tumors) -- iii) Progression of metastatic bone disease on bone scan with > 2 new lesions - Maintenance of Lupron or antagonist unless previously treated with orchiectomy - The presence of metastatic disease amenable to computed tomography (CT) or ultrasound guided biopsy; this may include thoracolumbar vertebral bodies, pelvis, femur or humerus, or soft tissue or nodal metastasis amenable to biopsy (excluding lung or pleural lesions) - Patients may have received secondary hormonal manipulations (excluding prior Abiraterone acetate, MDV3100 or TAK700) or up to two cycles of chemotherapy; all prior therapy except Lupron must have been discontinued for more than 4 weeks before enrollment - Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =< 1.5 x upper limit of normal (ULN) - Total bilirubin =< 1.5 x ULN - Calculated creatinine clearance >= 60 mL/min - Platelet count of >= 100,000/uL - Absolute neutrophil count of > 1,500 cell/mm^3 - Hemoglobin >= 9.0 g/dL Other eligibility criteria may apply. - Active infection or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated - Patients who are currently receiving active therapy for other neoplastic disorders will not be eligible - Patients with histologic evidence of small cell carcinoma of the prostate will not be eligible - Known brain metastasis - Uncontrolled hypertension (systolic blood pressure [BP] >= 160 mmHg or diastolic BP >= 95 mmHg); patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment - Active or symptomatic viral hepatitis or chronic liver disease - History of pituitary or adrenal dysfunction - Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class II-IV heart disease or cardiac ejection fraction measurement of < 50 % at baseline - Atrial fibrillation, or other cardiac arrhythmia requiring medical therapy - Administration of an investigational therapeutic within 30 days of screening - Patients with dementia/psychiatric illness/social situations that would limit compliance with study requirements or would prohibit the understanding and/or giving of informed consent will not be eligible - Patients with any condition that, in the opinion of the investigator, would compromise the well-being of the subject or the study or prevent the subject from meeting or performing study requirements - Patients unable to stop chronic anticoagulation for 3 days - Patients with poorly controlled diabetes - Patients with a history of gastrointestinal disorders (medical disorders or extensive surgery) that may interfere with the absorption of the study agents - Patients with a pre-existing condition that warrants long-term corticosteroid use in excess of study dose - Patients with known allergies, hypersensitivity, or intolerance to abiraterone acetate or prednisone or their excipients Other exclusion criteria may apply. 2aff090807ec1919906b9837f3c25ba3 9160 Capecitabine and Celecoxib With or Without Radiation Therapy in Treating Patients With Colorectal Cancer Previously Treated With Fluorouracil II Edward Lin, MD 7707 20; 73; 83 Colon Cancer; Rectal Cancer; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9160.html http://www.clinicaltrials.gov/ct/search?term=NCT01729923 NCT01729923 This phase II trial studies how well capecitabine and celecoxib with or without radiation therapy works in treating patients with metastatic colorectal cancer previously treated with fluorouracil. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Celecoxib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving capecitabine and celecoxib together with radiation therapy may kill more tumor cells Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Histologically confirmed colorectal cancer - Measurable radiographic evidence of colorectal cancer - Patients with unresected metastases from colorectal cancer; patients may be either untreated with chemotherapy or currently receiving first-line 5-FU based chemotherapy (folinic acid-fluorouracil-irinotecan [FOLFIRI], capecitabine-irinotecan [CAPIRI], fluorouracil-leucovorin calcium-oxaliplatin [FOLFOX], or capecitabine-oxaliplatin [CAPOX] with or without bevacizumab) within 6 months of study entry date with at least stable disease radiographically; patients who received prior adjuvant chemotherapy with 5-FU, capecitabine, or FOLFOX are eligible if adjuvant therapy was completed greater than 6 months ago - History of histological confirmation for recurrent disease, or if recurrent disease is not readily accessible to biopsy, must have two consecutive carcinoembryonic antigen (CEA) or cancer antigen (CA) 19-9 increases, or positron emission tomography (PET) avidity - Men and women from all ethnic and racial groups - Eastern Cooperative Oncology Group (ECOG) performance status =< 1 - Total bilirubin =< 1.5 x the institutional upper-normal limit (IUNL) - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and/or alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 x IUNL - Alkaline phosphatase =< 2.5 x IUNL - Leukocytes >= 3,000/uL - Absolute neutrophil count >= 1,000/uL - Platelets >= 100,000/uL - Women of childbearing age and all men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation - Negative urine pregnancy test for women of childbearing age - Must have the ability to understand and the willingness to provide a written informed consent to participate in the study Other eligibility criteria may apply. - History of allergies to sulfonamide, aspirin, any nonsteroidal anti inflammatory drugs (NSAIDS), 5-FU or celecoxib - Prior 5-FU-based adjuvant chemotherapy less than 6 months prior to study entry and any residual neuropathy > grade 2 - Any regular use of cyclooxygenase-2 (COX-2) inhibitors as defined by 2-3 times per week - Use of aspirin is NOT an exclusion criteria as long as the daily dose does not exceed 325 mg daily; initiation of ADAPT therapy requires patient to discontinue aspirin for 18 months - Pregnant or lactating women - History of significant neurologic or psychiatric disorders, including dementia or seizures that would impede consent, treatment, or follow up - Any serious illness or medical condition that could affect participation on trial - Any uncontrolled congestive heart failure New York Heart Association class III or IV - Any uncontrolled hypertension, arrhythmia, or active angina pectoris - Any history of major myocardial infarction, stroke or transient ischemic attack (TIA); minor acute myocardial infarction (AMI) and patients who have had cardiac bypass free of symptoms for at least 2 years may be eligible at the discretion of the study chair - Serious uncontrolled active infection - Patients with creatinine clearance: < 50 mL/min are excluded from this protocol; capecitabine is contraindicated in severe renal impairment (clearance < 40 mL/min) - Inability to swallow oral medications or any medical conditions that may affect intestinal absorption of the study agent or inability to comply with oral medication - History of active peptic ulcer disease or major upper gastrointestinal (GI) bleed < 12 months; history of GI bleeding from the colorectal cancer primary is not an exclusion criteria - Use of warfarin is not allowed; patient is recommended to switch to low molecular weight heparin (LMWH) before participating in this study - Patients with any history of brain or bone metastasis or who have develop progressive disease on first line 5-FU based therapy - Current use of steroid medication - Patients with an obstructive synchronous colorectal tumor requiring up-front surgery or chemoradiation - Patients with partial or complete bowel obstruction due to abdominal carcinomatosis Other exclusion criteria may apply. 23f13a7a8b8c5b5304986443ea622b07 9120 Memory and Thinking Skills Workshop in Improving Cognitive Rehabilitation in Ovarian Cancer Survivors Pilot Heidi Gray, MD 7750 65 Ovarian Cancer Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9120.html http://www.clinicaltrials.gov/ct/search?term=NCT01641068 NCT01641068 The purpose of this study is to examine thinking abilities, mood, and quality of life in cancer survivors before and after an 8-week group-based memory and thinking skills workshop. Research participants will include people treated for cancer in the past. Researchers would like to know if there is a relationship between baseline performance on timed attention and memory tasks before receiving memory and thinking skills workshop, and performance on such tasks after the workshop Ages Eligible for Study: 21 Years to 90 Years Genders Eligible for Study: Female - Subjective concern about declines in cognitive functioning related to a diagnosis of cancer and/or cancer related treatment - Prior treatment of ovarian cancer with chemotherapy - Completion of treatment (e.g., chemotherapy, radiation therapy, surgery, etc.) for ovarian cancer 6 months or greater in the past - Able to comprehend and speak English - For the subset of participants who will undergo magnetic resonance imaging (MRI), ability to withstand lying down in small area (MRI scanner) for 50 minutes - Completion of successful fMRI safety screening - Able to give informed consent - Able to undergo informed consent procedures and 3 hours of testing, plus 8 1-hour cognitive rehabilitation sessions with breaks Other eligibility criteria may apply. - Ongoing treatment for ovarian or other cancer (e.g., chemotherapy, radiation, surgery, etc.) - Cancer onset before the age of 21 - Unstable medical problems (such as unstable heart disease, unstable hypertension, diabetes in poor control, respiratory disease complicated by hypoxia or hypercapnia, infectious illnesses, unstable thyroid dysfunction, currently hospitalized) - History of, or current symptoms of, serious psychiatric disorder requiring antipsychotic medications or hospitalization; mild depression or stable anti-depressants, and anti-seizure medications are acceptable; anti-anxiety medications are not - Current alcohol over-use as defined by currently consuming 4 drinks or more per day or binge drinking (6 or more drinks in one night) within the past week - Current substance use or abuse as defined by any recreational drug use (e.g. cocaine, methamphetamine, crack, hashish, heroin, acid, mushrooms and others that may not be listed here but are determined to be adverse according to PI) as well as any use of marijuana regardless of medical prescription - History of or current neurological illness that significantly impacts cognition (e.g. stroke, multiple sclerosis, Parkinson's disease, Alzheimer's disease, head injury, epilepsy, etc) - History of brain injury that significantly impacted cognition; as indicated responses on the Ohio State University Traumatic Brain Injury Identification Method (OSU TBI-ID) greater or equal to any of the following: 30 minutes or more of LOC, two or more mild cases within two weeks of each other, or any injury with loss of consciousness before the age of 15 - History of central nervous system (CNS) tumor - A score of 25 or more on the Patient Health Questionnaire (PHQ-9) on the first visit - A score of 26 or below on the Mini Mental Status Exam (MMSE) - A score above 45 on the Wender Utah Rating Scale for ADD (WURS) - For the subset of participants undergoing neuroimaging: - Medical history or devices which make an MRI unsafe or uncomfortable (e.g., magnetic rods or pins, metal plates or screws, pacemaker) Other exclusion criteria may apply. 869bf9f0c2515cd75437792eda84a19c 9168 Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients With Previously Treated Advanced Non-Small Cell Lung Cancer II Christina Baik 7755 46; 83 Lung Cancer; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9168.html http://www.clinicaltrials.gov/ct/search?term=NCT01620190 NCT01620190 This research study examines the use of Abraxane (paclitaxel albumin-stabilized nanoparticle formulation) in patients with lung cancer. Abraxane is a chemotherapy approved to treat patients with breast cancer. Doctors want to know if Abraxane is safe and effective in treating patients with advanced lung cancer and epidermal growth factor receptor (EGFR) mutations Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Pathologically confirmed non-small cell lung cancer with documented EGFR mutation in tumor deoxyribonucleic acid (DNA) - At least one site of measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) - Progressive disease with radiographic evidence of disease progression per investigator assessment during therapy with an EGFR tyrosine kinase inhibitor in the metastatic setting; patients may continue EGFR inhibitor therapy throughout the screening period until the day prior to nab-paclitaxel treatment initiation - Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 at the time of informed consent - Platelet count >= 100,000/UL - Absolute neutrophil count >= 1,500/UL - Hemoglobin >= 9g/dL - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = < 2.5 times upper limit of normal - Alkaline phosphatase =< 2.5 times upper limit of normal, unless bone metastasis is present in the absence of liver metastasis - Bilirubin =< 1.5mg/dL - Creatinine =< 1.5mg/dL - Women of child-bearing potential (WOCP) and sexually active men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry, during treatment and for three months after completing treatment - Negative serum or urine beta-human chorionic gonadotropin (hCG) pregnancy test at screening for patients of childbearing potential - Life expectancy of >= 12 weeks - Signed and dated informed consent document indicating that the patient has been informed of all the pertinent aspects of the trial prior to enrollment Other eligibility criteria may apply. - Prior conventional cytotoxic chemotherapy for metastatic or recurrent disease; prior adjuvant, neoadjuvant or chemoradiotherapy for NSCLC is permitted, provided at least 6 months elapsed prior to documented metastatic recurrence - Patient is < 5 years free of another primary malignancy, except: a) if the other malignancy is basal cell carcinoma or cervical carcinoma in situ or b) if the other primary malignancy is not considered clinically significant and is requiring no active intervention - Progressive or symptomatic central nervous system (CNS) metastases; patients with known brain metastasis must have stable disease following treatment with surgery, radiation or both; in addition, they must be off corticosteroids - Radiotherapy within 7 days of study treatment - Peripheral neuropathy grade 2 or greater - Grade III/IV congestive heart failure, as defined by New York Heart Association (NYHA) criteria, or myocardial infarction within 6 months - Any serious or uncontrolled concomitant disorder that, in the opinion of the investigator, would compromise the patient's ability to complete the study - Patient has known chronic liver disease, e.g. diagnosis of chronic active hepatitis or cirrhosis - Major surgery within 21 days of study treatment; minor surgery within 2 weeks of study treatment; placement of vascular access device and biopsies allowed and is not considered major or minor surgery - Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent - Pregnant or breast feeding females Other exclusion criteria may apply. 74cf168c8c38318ee26e8db0daec8c4e 9227 Induction Chemotherapy for Locally Advanced Squamous Cell Carcinoma of the Head and Neck II Renato Martins, MD, MPH 7797 35; 83 Head and Neck Cancer; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9227.html http://www.clinicaltrials.gov/ct/search?term=NCT01412229 NCT01412229 This is a non-randomized, open-label phase II trial of 40 patients with poor prognosis head and neck cancer, defined as surgically unresectable and/or = or > N2b disease and judged appropriate for non-surgical definitive therapy. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Histologically or cytologically confirmed SCCHN or poorly differentiated or undifferentiated cancer of the head and neck. - Measurable disease. - All primary sites are eligible excluding nasopharyngeal. - Surgically unresectable and/or N2b or greater nodal disease; NOTE: surgical unresectability will be defined as the combination of the treating surgeon's judgment of unresectability plus one of the following objective criteria: --- Encasement of tumor or nodes to the carotid artery or ¾ encasement of the carotid artery. --- Involvement of prevertebral musculature --- Invasion of the bone of the skull base --- Need for glossectomy or extensive glossal resection where functional outcome is considered unacceptable to surgeon or patient --- Involvement of the cervical spine --- Severe, unacceptable functional deficit that would result from any proposed definitive surgical resection. - ECOG performance status 0-1 - Prior therapy: --- Chemotherapy: No prior chemotherapy for the treatment of SCCHN. --- Platinum chemotherapy: No previous history of carboplatin or cisplatin therapy. --- Nab-paclitaxel: No previous treatment with nab-paclitaxel or another taxane. --- Cetuximab: No previous treatment with cetuximab Or another EGFR inhibitor. --- Radiation therapy: No prior radiation to the head and neck region. - Age > or = 18 years. Men and women are eligible for participation. - Must have acceptable organ and marrow function as defined below. Laboratory tests should be completed within 14 days prior to registration: --- ANC > or = 1,500/mm3 --- Platelets > or = 100,000/mm3 --- HgB > 9g/dL --- Total bilirubin < or = 1.5mg/dL --- Albumin > 2.5 g/dL --- AST(SGOT)/ALT(SGPT) < or = 2.5X institutional upper limit of normal, alkaline phosphatase < 2.5 x upper limit of normal, GFR > 30 mL/min (by standard Cockcroft and Gault formula or measured via 24 hour urine collection) - No pre-existing neuropathy greater than grade I - Women of childbearing potential must have a negative serum or urine pregnancy test performed within 7 days prior to day 1 of study treatment. - Women of childbearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation and for three months after completing treatment. Adequate contraception is defined as any medically recommended method (or combination of methods) as per standard of care. - Patients must have the ability to understand and the willingness to sign a written informed consent document. - Patients must have a negative result for preformed IgE antibodies to galactose-alpha-1,3,-galactose. Other eligibility criteria may apply. - Prior treatment with any of the study medications. - Prior radiation to any of the field required to treat the tumor. - Any metastatic disease. - The patient may have had a prior malignancy but must be disease-free for three years prior to study entry. A history of superficial non-melanoma skin cancer or in situ carcinoma of the cervix less than three years will be allowed. - Pregnant or lactating female - Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring IV antibiotics, or psychiatric illness/social situations that would limit compliance with study requirements. Cardiac disease such as symptomatic congestive heart failure, unstable angina pectoris, or myocardial infarction will result in exclusion only if active within the past six months. Cardiac dysrhythmia will only result in exclusion if active and symptomatic (for example, rate-controlled atrial fibrillation will not result in exclusion). Other exclusion criteria may apply. 0900f35bf5d349d566740dbdd9d1f89b 9376 Brentuximab Vedotin in Treating Patients With Relapsed or Refractory CD30+ Lymphoma Pilot Ajay Gopal, MD 7808 36; 43; 48 Hematologic Malignancies; Leukemia; Lymphoma Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9376.html http://www.clinicaltrials.gov/ct/search?term=NCT01703949 NCT01703949 This pilot clinical trial studies brentuximab vedotin in treating patients with relapsed or refractory cluster of differentiation (CD)30+ lymphoma. Biological therapies, such as brentuximab vedotin, may stimulate the immune system in different ways and stop cancer cells from growing Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Relapsed or refractory CD30+ lymphoma that has either achieved < PR to brentuximab vedotin (minimum of 2 cycles) or progressed while receiving brentuximab vedotin - Documented expression of CD30 on tumor cells following the last dose of brentuximab vedotin - Absolute neutrophil count (ANC) > 1,000/uL - Platelets > 50,000/uL - Serum creatinine < 1.5 mg/dL OR creatinine clearance > 60 mL/min - Bilirubin < 1.5 x upper limit of normal (ULN) - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x ULN - Measurable disease by computed tomography (CT) or similar (e.g. magnetic resonance imaging [MRI]) criteria (> 1.5 cm) - Resolution of all non-hematologic brentuximab vedotin-related adverse events (AEs) to < Grade 2 - All patients must be informed of the investigational nature of this study and have given written consent in accordance with institutional and federal guidelines - Patients must be anticipated to complete at least 2 cycles of chemotherapy on study - Expected survival if untreated of > 90 days Other eligibility criteria may apply. - Prior transplant within 100 days - Radioimmunotherapy within 12 weeks - Known human immunodeficiency virus (HIV) or hepatitis B positivity - Active infection or other medical condition which would preclude treatment in the opinion of the principal investigator - Eastern Cooperative Oncology Group (ECOG) performance status > 2 - Known active central nervous system (CNS) involvement - Peripheral neuropathy > Grade 1 if due to brentuximab vedotin or any peripheral neuropathy > Grade 2 - Intolerance to brentuximab vedotin - Concurrent use of other anti-cancer agents or experimental treatments Other exclusion criteria may apply. 5b498c496c3a878fd6bc01d0ca73fca6 9340 Cabozantinib in Treating Men With Hormone-Resistant Prostate Cancer Pilot Tia Higano, MD 7819 71; 83 Prostate Cancer; Solid Tumors Teresa Gambol 206/288-6452 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9340.html http://www.clinicaltrials.gov/ct/search?term=NCT01703065 NCT01703065 This pilot clinical trial studies cabozantinib in treating men with hormone-resistant prostate cancer. Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Male Key Inclusion Criteria: - The subject has a proven histologic diagnosis of prostate adenocarcinoma, but may have undergone prior surgery and/or radiation - The subject must currently have castration resistant prostate cancer defined as 2 serial rising prostate-specific antigens (PSAs) with a castrate level of testosterone (< 50 ng/dL) - A subject with non-metastatic castration-resistant prostate cancer (CRPC) may not have received prior chemotherapy unless in the neoadjuvant or adjuvant setting > 24 months ago and may not have received prior zoledronic acid or denosumab - A subject with metastatic CRPC must have bone metastases accessible for biopsy by computed tomography (CT) guidance - The subject must be willing to undergo sequential biopsy of bone or bone metastases - Adequate organ and bone marrow function. - The subject is capable of understanding and complying with the protocol requirements and has signed the informed consent document Other eligibility criteria may apply. Key Exclusion Criteria: - Prior treatment with cabozantinib and other met inhibitors - Cytotoxic chemotherapy or biologic agents within 3 weeks of study treatment - Recent radiation therapy (3 months for thoracic cavity, 14 days for bone or brain metastasis, 28 days for other sites) or radionuclide treatment within 6 weeks of starting study drug. - The subject has received any other type of investigational agent within 28 days before the first dose of study treatment - The subject has not recovered from toxicities due to all prior therapies except alopecia and other non-clinically significant adverse events (AEs) - The subject has primary brain tumor or active brain metastases or epidural - Coagulation tests need to be adequate for the study - The subject requires concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, heparin, thrombin or Factor Xa inhibitors, or antiplatelet agents (eg, clopidogrel); low dose aspirin (=< 81 mg/day), low-dose warfarin (=< 1 mg/day), and prophylactic low molecular weight heparin (LMWH) are permitted - The subject requires chronic concomitant treatment of strong cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, and St. John's Wort) - History of clinically significant gastrointestinal bleeding - The subject has uncontrolled, significant intercurrent or recent illness - The subject is unable to swallow tablets - The subject has a corrected QT interval (QTcF) > 500 ms within 28 days before day 1 of cycle 1 - The subject has a previously identified allergy or hypersensitivity to components of the study treatment formulation or to tetracycline Other exclusion criteria may apply. 1c4205c24f5205d80c9ea4f829e7272b 9358 Vorinostat in Treating Patients With Stage IV Breast Cancer Receiving Hormone Therapy Pilot Hannah Linden, MD 7841 13; 83 Breast Cancer; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9358.html http://www.clinicaltrials.gov/ct/search?term=NCT01720602 NCT01720602 This pilot clinical trial studies vorinostat in treating patients with stage IV breast cancer receiving hormone therapy. Vorinostat may help hormone therapy work better by making tumor cells more sensitive to the drug Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Histologically or cytologically proven diagnosis of breast cancer - Stage IV disease - Patient has previously derived clinical benefit from endocrine therapy, but is no longer deriving benefit to endocrine therapy in the opinion of the treating investigator - At least one site of measurable disease, as defined by the modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria - Eastern Cooperative Oncology Group (ECOG) performance status 0-2 - Female patient is post menopausal as defined by one of the following: - * free from menses for >= 2 years, surgically sterilized, FSH and estradiol in post-menopausal range AND surgical absence of uterus OR - * chemotherapy induced amenorrhea lasting > 1 year OR currently on ovarian suppression - Female patient of childbearing potential has a negative urine or serum (beta human chorionic gonadotropin [B-hCG]) pregnancy test within 14 days prior to receiving the first dose of vorinostat - Male patient agrees to use two barrier methods of contraception or abstain from intercourse for the duration of the study - Absolute neutrophil count (ANC) >= 1,500/mcL - Platelets >= 100,000/mcL - Hemoglobin >= 9 g/dL - Prothrombin time or international normalized ratio (INR) =< 1.5 x upper limit of normal (ULN) unless receiving therapeutic anticoagulation - Partial thromboplastin time (PTT) =< 1.2 times the ULN unless the patient is receiving therapeutic anticoagulation - Potassium (K) levels normal limits - Magnesium (Mg) levels normal limits - Calculated creatinine clearance >= 30 mL/min - * Creatinine clearance should be calculated per institutional standard - Serum total bilirubin =< 1.5 x ULN - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 x ULN - Alkaline phosphatase =< 2.5 x ULN - Patient, or the patient's legal representative, has voluntarily agreed to participate by giving written informed consent - Patient has a life expectancy of at least 12 weeks in the opinion of the treating investigator - Patient is willing to continue on same AI therapy - Patient agrees to participate in imaging protocol 7184 and is separately consented Other eligibility criteria may apply. - Patient has not derived clinical benefit from prior endocrine therapy - Patient is currently participating or has participated in a study with an investigational compound or device within 30 days of initial dosing with study drug(s) other than the imaging protocol 7184 - Patient has received an ER blocking therapy (selective estrogen receptor modulating or downregulating selective estrogen receptor modulator [SERM] or selective estrogen receptor degrader [SERD] i.e. tamoxifen or fulvestrant) within the past 6 weeks - Patient had prior treatment with an histone deacetylase (HDAC) inhibitor (e.g., romidepsin [Depsipeptide], NSC-630176, MS 275, LAQ-824, belinostat (PXD-101), LBH589, MGCD0103, CRA024781, etc); patients who have received compounds with HDAC inhibitor-like activity, such as valproic acid, as anti-tumor therapy should not enroll in this study; patients who have received such compounds for other indications, e.g. valproic acid for epilepsy, may enroll after a 30-day washout period - Patient is on any systemic steroids that have not been stabilized to the equivalent of =< 10 mg/day prednisone during the 30 days prior to the start of the study drugs - Patient has known hypersensitivity to the components of study drug or its analogs - Patients with uncontrolled brain metastases - New York Heart Association (NYHA) class III or IV congestive heart failure, myocardial infarction within the previous 6 months, QTc > 0.47 seconds, or uncontrolled arrhythmia - Type I diabetes mellitus; patients with type II diabetes mellitus will be included as long as their glucose can be controlled to under 200 mg/dL - Patient is pregnant or breast feeding, or expecting to conceive or father children within the projected duration of the study - Patient with a "currently active" second malignancy, other than non-melanoma skin cancer and carcinoma in situ of the cervix, should not be enrolled; patients are not considered to have a "currently active" malignancy if they have completed therapy for a prior malignancy, are disease free from prior malignancies for > 5 years or are considered by their physician to be at less than 30% risk of relapse - Patients with known active viral hepatitis - Patient has a history or current evidence of any condition, therapy, or laboratory (lab) abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study or is not in the best interest of the patient to participate Other exclusion criteria may apply. 0b857da1ac327d24fccba180ff793310 9413 Abiraterone Acetate and Prednisone With or Without Veliparib in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer II Robert Montgomery, MD 7847 71; 83 Prostate Cancer; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9413.html http://www.clinicaltrials.gov/ct/search?term=NCT01576172 NCT01576172 This randomized phase II trial studies abiraterone acetate and prednisone together with veliparib to see how well it works compared to abiraterone acetate and prednisone alone in treating patients with metastatic hormone-resistant prostate cancer. Androgens can cause the growth of prostate cancer cells. Antiandrogen drugs, such as abiraterone acetate, may lessen the amount of androgens made by the body. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether giving abiraterone acetate together with prednisone and veliparib is more effective than abiraterone acetate and prednisone alone in treating prostate cancer Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Male - Have a histologic or cytologic diagnosis of prostate cancer - Have progressive metastatic castration-resistant prostate cancer, on androgen-deprivation therapy, based on at least one of the following criteria: --- Prostate-specific antigen (PSA) progression defined as 25% increase over baseline value with an increase in the absolute value of at least 2 ng/mL that is confirmed by another PSA level with a minimum of a 1-week interval with a minimum PSA of 2 ng/mL --- Progression of bidimensionally measurable soft tissue (nodal metastasis) assessed within one month prior to registration by a computed tomography (CT) scan or magnetic resonance imaging (MRI) of the abdomen and pelvis --- Progression of bone disease (evaluable disease) (new bone lesion[s]) by bone scan - Agree to undergo a biopsy of >= 1 metastatic site for gene-fusion status --- Adequate archival metastatic tissue can be used if available in lieu of a biopsy; patients will only be eligible for protocol therapy if the biopsy has tumor and the tissue is evaluable for ETS fusion status - Have testosterone < 50 ng/dL; patients must continue primary androgen-deprivation with a luteinizing hormone-releasing hormone (LHRH) analogue if they have not undergone orchiectomy - Patients with known brain metastases should be excluded from this clinical trial - Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 - White blood cells >= 3,000/uL - Absolute neutrophil count >= 1,500/uL - Platelet count >= 100,000/uL - Creatinine within the institutional limits of normal - Potassium >= 3.5 mmol/L - Bilirubin within the institutional limits of normal - Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 2 times upper limit of normal - Serum glutamic pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2 times upper limit of normal - Must agree to use effective contraception during treatment and for at least 1 week after the last administration of therapy - Patients must be able to take oral medication without crushing, dissolving, or chewing tablets - Ability to understand and the willingness to sign a written informed-consent document that is approved by the local institutional review board - Patients with history of active seizures are not eligible - Patients with a history of pituitary or adrenal dysfunction, active or symptomatic viral hepatitis, or chronic liver disease are not eligible - No history of allergic reactions attributed to compounds of similar chemical or biologic composition to ABT-888 or abiraterone - No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association class III and IV heart failure), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements or concurrent medications that alter cardiac conduction - Patients with a "currently active" second malignancy other than non-melanoma skin cancers are not eligible; patients are not considered to have a "currently active" malignancy if they have completed all therapy and are now considered without evidence of disease for 1 year - Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible - Patients must discontinue antiandrogen therapy for at least 4 weeks (e.g., flutamide, bicalutamide, nilutamide) prior to registration with no evidence of a falling PSA after washout; patients on steroids are eligible as long as they will be switched to prednisone - Have no prior exposure to cytochrome P450, family 17, subfamily A, polypeptide 1 (CYP-17) or poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors - Patients with up to 2 prior chemotherapy regimens are eligible - Patients may have received prior radiation therapy or surgery; however, at least 21 days must have elapsed since completion of radiation therapy or surgery and patient must have recovered from all side effects at the time of registration - Patients may not be receiving any other investigational agents; any prior investigational products must be stopped at least 14 days (2-week washout) prior to registration - No patients who have had chemotherapy or antifungal agents (itraconazole, fluconazole) within 3 weeks prior to entering the study or those who have not recovered (e.g., back to baseline or grade 1) from adverse events due to agents administered more than 3 weeks earlier - Patients may continue on a daily multivitamin, calcium, and vitamin D, but all other herbal, alternative, and food supplements (i.e., PC-SPES, saw palmetto, St. John wort, etc.) must be discontinued before registration - Patients must not be planning to receive any concurrent cytotoxic chemotherapy, surgery, or radiation therapy during protocol treatment - Hormonal-acting agents (including diethylstilbestrol [DES], aldosterone, and spironolactone) are forbidden during the trial and must be stopped prior to registration; no washout period will be required for any of these agents - Patients on stable doses of bisphosphonates or denosumab which have been started prior to registration may continue on this medication, patients who are not on bisphosphonates or denosumab are eligible as long as they initiate therapy prior to registration Other eligibility criteria may apply. Other exclusion criteria may apply. a029cd6b4160e57a02daec8b70ab7ab8 9431 Vaccine Therapy in Treating Patients With Stage IV Hormone Receptor Positive Breast Cancer II Lupe Salazar, MD 7905 13; 83 Breast Cancer; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9431.html http://www.clinicaltrials.gov/ct/search?term=NCT01729884 NCT01729884 This phase II trial studies how well vaccine therapy works in treating patients with stage IV hormone receptor positive breast cancer. Vaccines made from peptides may help the body build an effective immune response to kill tumor cells Ages Eligible for Study: 19 Years and older Genders Eligible for Study: Both - Patients with HER2+ stage IV breast cancer that have been maximally treated and not in a complete remission - Patients must have measurable disease per imaging studies performed within 60 days of enrollment as described below: --- Extra skeletal disease that can be measured with conventional or spiral computed tomography (CT) techniques -- Skeletal or bone-only disease that is measurable by fludeoxyglucose F 18 (FDG) positron emission tomography (PET) or magnetic resonance imaging (MRI) - Patients can be receiving trastuzumab and/or lapatinib and/or hormonal therapy and/or bisphosphonate therapy - HER2 overexpression in the primary tumor or metastasis by immunohistochemistry (IHC) of 3+, or documented gene amplification by fluorescent in situ hybridization (FISH) analysis - Patients must be human leukocyte antigen (HLA)-A2 positive - Eastern Cooperative Oncology Group (ECOG)/Zubrod scale of =< 1 - Patients must be off immunosuppressive treatments (i.e., chemotherapy or systemic steroids) 3 weeks prior to first vaccine - Patients on trastuzumab must have a baseline left ventricular ejection fraction (LVEF) measured by multi gated acquisition scan (MUGA) or echocardiogram (ECHO) >= the lower limit of normal for the facility within 3 months of enrollment to study - Subjects of reproductive ability must agree to use contraceptives during the entire study period Other eligibility criteria may apply. - White blood cell (WBC) < 3000/mm^3 - Hemoglobin (Hgb) < 10 mg/dl - Platelets < 100,000/mm^3 - Serum creatinine > 2.0 mg/dl - Serum bilirubin > 1.5 x upper limit of normal - Any contraindication to receiving sargramostim (GM-CSF) based vaccine products - Concurrent enrollment in other treatment studies - New York Heart Association functional class III-IV heart failure, symptomatic pericardial effusion, or unstable angina - Pregnant or breast-feeding women - History of disorders associated with immunosuppression such as human immunodeficiency virus (HIV) - Active brain metastasis Other exclusion criteria may apply. b179aec31e251480c3723256cb2cae5a 6980 III Blythe Thomson, MD CHRMC 2006 1; 36; 43 Acute Lymphoid Leukemia (ALL); Hematologic Malignancies; Leukemia Seattle Children’s Outpatient Attending MD (206) 987-2106 http://cancer.seattlechildrens.org/ http://www.fhcrc.org/en/treatment/clinical-trials/detail.6980.html http://www.clinicaltrials.gov/ct/search?term=NCT00550992 NCT00550992 4881811e96fc029acd82ee36e4278b42 7090 III James Olson, MD, PhD COG ACNS0332 12; 33; 51; 70; 83 Brain Cancer; Glioma; Medulloblastoma; Primitive Neuroectodermal Tumor (PNET); Solid Tumors Seattle Children’s Outpatient Attending MD (206) 987-2106 http://curesearch.org/; http://cancer.seattlechildrens.org/home/ http://www.fhcrc.org/en/treatment/clinical-trials/detail.7090.html http://www.clinicaltrials.gov/ct/search?term=NCT00392327 NCT00392327 b38fbfd79ca8b07b061b779b6191270e 5458 III Doug Hawkins, MD COG AEWS0331 77; 83 Sarcoma; Solid Tumors Seattle Children’s Outpatient Attending MD (206) 987-2106 http://www.curesearch.org; http://cancer.seattlechildrens.org/home/ http://www.fhcrc.org/en/treatment/clinical-trials/detail.5458.html http://www.clinicaltrials.gov/ct/search?term=COG+AEWS0331 COG+AEWS0331 84a08a9e00fb62a4087a2d4feec59537 7267 III Julie Park, MD COG ANBL0532 63; 83 Neuroblastoma; Solid Tumors Seattle Children’s Outpatient Attending MD (206) 987-2106 http://curesearch.org/; http://cancer.seattlechildrens.org/ http://www.fhcrc.org/en/treatment/clinical-trials/detail.7267.html http://www.clinicaltrials.gov/ct/search?term=NCT00567567 NCT00567567 5815b62f24e346b54ca4e972ce5c2e1f 7015 III Doug Hawkins, MD COG ARST0531 77; 83 Sarcoma; Solid Tumors Seattle Children’s Outpatient Attending MD (206) 987-2106 http://curesearch.org/; http://cancer.seattlechildrens.org/ http://www.fhcrc.org/en/treatment/clinical-trials/detail.7015.html http://www.clinicaltrials.gov/ct/search?term=NCT00354835 NCT00354835 d1145aef73952a289b33fbf973252566 8135 III Benjamin Greer, MD GOG 0724/ RTOG 0724 17; 34; 83 Cervical Cancer; Gynecological Cancer; Solid Tumors Monica Dherin 206/667-4696 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8135.html http://www.clinicaltrials.gov/ct/search?term=NCT00980954 NCT00980954 ac87092d3566aae8e8924f0ecdfb5b8a 7686 Vorinostat, Fludarabine Phosphate, Cyclophosphamide, and Rituximab in Treating Patients With Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic I/II John Pagel, MD, PhD PSOC 2401 18; 36; 43; 48 Chronic Lymphoid Leukemia (CLL); Hematologic Malignancies; Leukemia; Lymphoma Britt Kammerer, CTR 206/667-4174 http://www.fhcrc.org/en/treatment/clinical-trials/detail.7686.html http://www.clinicaltrials.gov/ct/search?term=NCT00918723 NCT00918723 This phase I/II trial is studying the side effects and best dose of vorinostat when given together with fludarabine phosphate, cyclophosphamide, and rituximab and to see how well it works in treating patients with previously untreated B-cell chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as fludarabine phosphate and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block the growth of cancer in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving vorinostat together with fludarabine phosphate, cyclophosphamide, and rituximab may kill more cancer cells Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Patients must have a confirmed diagnosis of CLL/SLL - Patients with previously untreated cluster of differentiation (CD)20+ CLL/SLL must have either Rai stage III/IV disease or be Rai stage I/II with evidence of disease activity as defined by the National Cancer Institute (NCI) 1996 guidelines; patients with SLL must be Stage III or IV per Ann Arbor staging system - Patient must have consented to participate in the study and signed and dated an appropriate institutional review board (IRB)-approved consent form that conforms to federal and institutional guidelines - Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 - Patient must have an anticipated (untreated) survival of at least 3 months - Female patient of childbearing potential has a negative serum pregnancy test beta-human chorionic gonadotropin (hCG) within 72 hours prior to receiving the first dose of vorinostat - Female patient is either post menopausal, free from menses for >= 2 years, surgically sterilized or willing to use 2 adequate barrier methods of contraception to prevent pregnancy or agrees to abstain from heterosexual activity throughout the study, starting with Visit 1 - Male patients not sterilized must be willing to use adequate barrier methods of contraception to prevent pregnancy or agrees to abstain from heterosexual activity throughout the study, starting with Visit 1 - Absolute Neutrophil Count (ANC) >= 1,500/mcL - Platelets >= 100,000/mcL - Hemoglobin >= 9 g/dL - Prothrombin time or international normalized ratio (INR) =< 1.5 upper limit of normal (ULN) unless receiving therapeutic anticoagulation - Partial thromboplastin time (PTT) =< 1.2 times the ULN unless the patient is receiving therapeutic anticoagulation - Potassium level within normal limits - Magnesium level within normal limits - Serum creatinine =< 1.5 x ULN OR if creatinine is > 1.5 ULN the calculated creatinine clearance must be >= 60 mL/min - Serum total bilirubin =< 1.5 times ULN; patients with Gilbert's disease or similar syndrome involving slow conjugation of bilirubin are eligible with total bilirubin > 1.5 times upper limit of normal; primary investigator (PI) review and approval required for anything above 2 times ULN - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 ULN - Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 ULN - Alkaline Phosphatase =< 2.5 ULN - Patients with cytopenias due to disease or pseudohyperkalemia that do not meet these criteria, will be considered eligible with review and approval by the PI or Co-PI prior to study entry Other eligibility criteria may apply. - Patients who have received cytotoxic chemotherapy, radiation therapy, immunotherapy, or cytokine treatment prior to study entry for CLL/SLL; patients who have received systemic steroids within 1 week of study entry are excluded, except patients on maintenance steroid therapy for a noncancerous disease - Patients with active hemolysis - Patients must not require sustained transfusion support of blood products - Patients who have undergone treatment with either stem cell or bone marrow transplant - Patients with active obstructive hydronephrosis - Patients with evidence of any significant systemic illness, active Hepatitis B infection, active viral hepatitis infection or other active infection at the time of study entry - Patients with New York Heart Association class III or IV heart disease symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or other serious illness, such as acute or chronic graft versus host disease, that would preclude evaluation - Patients with congenital long QT syndrome and patients taking antiarrhythmic medicines or other medicinal products that lead to QT prolongation will only be eligible if their baseline QTc prolongation is =< 500 msec - Patients with known human immunodeficiency virus (HIV) infection - Patients who are pregnant or nursing - Patients with known brain or leptomeningeal involvement by malignancy - Patients who have, in the opinion of the investigator, other medical, social, or psychosocial factors that may negatively impact compliance or their safety by participation in this study - Patient is currently participating or has participated in a study with an investigational compound or device within 30 days of initial dosing with study drugs(s) - Patient had prior treatment with an histone deacetylases (HDAC) inhibitor (e.g., romidespin (Depsipeptide), NSC-630176, MS 275, LAQ-824, belinostat (PXD-101), LBH589, MGCD0103, CRA024781, etc); patients who have received compounds with HDAC inhibitor-like activity, such as valproic acid, as anti-tumor therapy should not enroll in this study; patients who have received such compounds for other indications, e.g. valproic acid for epilepsy, may enroll after a 30-day washout period - Patient with a history of a prior malignancy with the exception of cervical intraepithelial neoplasia; non-melanoma skin cancer; adequately treated localized prostate carcinoma with prostate-specific antigen (PSA) =< 1.0; or who has undergone potentially curative therapy with no evidence of that disease for five years, and/or who is deemed at low risk for recurrence by his/her treating physician Other exclusion criteria may apply. 3b16c7e87280da7a9c769bb18c7f22cb 2330 Pentostatin and Lymphocyte Infusion in Preventing Graft Rejection in Patients Who Have Undergone Donor Stem Cell Transplant I/II Brenda Sandmaier, MD 1825.00 1; 2; 18; 19; 36; 38; 43; 48; 57; 61; 64 Acute Lymphoid Leukemia (ALL); Acute Myeloid Leukemia (AML); Chronic Lymphoid Leukemia (CLL); Chronic Myeloid Leukemia (CML); Hematologic Malignancies; Hodgkin's Lymphoma; Leukemia; Lymphoma; Multiple Myeloma (MM); Myelodysplastic and Myeloproliferative Syndromes (MDS and MPD); Non-Hodgkin's Lymphoma (NHL) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.2330.html http://www.clinicaltrials.gov/ct/search?term=NCT00096161 NCT00096161 This clinical trial studies pentostatin and donor lymphocyte infusion in preventing graft rejection in patients who have undergone donor stem cell transplant. Giving pentostatin and an infusion of the donor's T cells (donor lymphocyte infusion) after a donor stem cell transplant may stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving pentostatin before donor lymphocyte infusion may stop this from happening Genders Eligible for Study: Both - Only patients having received a preceding nonmyeloablative allogeneic transplantation with fludarabine/2-3 Gy total-body irradiation (TBI) or 2 Gy TBI conditioning from either a related or unrelated donor are eligible for this protocol - Patients with less than 50% donor CD3 peripheral blood chimerism on two separate, consecutive evaluations (the two evaluations must be at least 14 days apart) OR patients with absolute decreases of donor CD3 peripheral blood chimerism of >= 20% if the second test shows < 50% donor CD3 cells (the two evaluations must be at least 14 days apart) - Patients with evidence of disease are only eligible if the disease is stable (or persistent) in comparison to the status prior to transplantation - Patients must be tapered off systemic steroids to a dosage of less than or equal to 0.25 mg/kg/day; additionally, all other immunosuppressive therapy will be discontinued before administration of pentostatin - Patients must have persistent donor CD3 cells (>= 5% donor CD3 cells by a deoxyribonucleic acid (DNA)-based assay that compares the profile of amplified fragment length polymorphisms [ampFLP] [or fluorescent in situ hybridization (FISH) studies or variable number of tandem repeats (VNTR)]) - DONOR: Alternatively to a fresh unmodified leukapheresis product, previously collected cryopreserved peripheral blood stem cells (PBSC) after mobilization with G-CSF or cryopreserved unmodified leukapheresis product from the original donor can be used; if cryopreserved product is not available, the following criteria apply for the DLI product: - DONOR: Original donor of hematopoietic cell transplantation - DONOR: Donor must give consent to leukapheresis - DONOR: Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral or subclavian) - DONOR: Donor must be medically fit to undergo the apheresis procedure (institutional guidelines for apheresis) Other eligibility criteria may apply. - Current grade II to IV acute GVHD or extensive chronic GVHD - Karnofsky score < 50% - Lansky Play-Performance Score < 40 - Evidence of relapse or progression of disease after transplantation - DONOR: Donor who are not suitable for medical reasons to donate peripheral blood mononuclear cells (PBMC) by continuous centrifugation according to the criteria of the American Association of Blood Banks (AABB) - DONOR: Pregnancy - DONOR: Human immunodeficiency virus (HIV) or human T-lymphotrophic virus (HTLV) infection - DONOR: Recent immunization may require a delay Other exclusion criteria may apply. b29d254b6c9d561ede377eb2e500e6c0 5582 Tacrolimus and Mycophenolate Mofetil in Preventing Graft-Versus-Host Disease in Patients Who Have Undergone Total-Body Irradiation With or Without Fludarabine Phosphate Followed by Donor Peripheral Blood Stem Cell Transplant For Hematologic Cancer II David Maloney, MD, PhD 1898.00 1; 2; 11; 18; 19; 36; 38; 43; 48; 57; 61; 64 Acute Lymphoid Leukemia (ALL); Acute Myeloid Leukemia (AML); Bone Marrow and Hematopoietic Stem Cell Transplant (BMT and HSCT); Chronic Lymphoid Leukemia (CLL); Chronic Myeloid Leukemia (CML); Hematologic Malignancies; Hodgkin's Lymphoma; Leukemia; Lymphoma; Multiple Myeloma (MM); Myelodysplastic and Myeloproliferative Syndromes (MDS and MPD); Non-Hodgkin's Lymphoma (NHL) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.5582.html http://www.clinicaltrials.gov/ct/search?term=NCT00089011 NCT00089011 This phase II trial is studying how well giving tacrolimus together with mycophenolate mofetil works in preventing graft-versus-host disease in patients who have undergone total-body irradiation (TBI) with or without fludarabine phosphate followed by donor peripheral blood stem cell transplant for hematologic cancer. Giving low doses of chemotherapy, such as fludarabine phosphate, and TBI before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus and mycophenolate mofetil after transplant may stop this from happening. Ages Eligible for Study: up to 74 Years Genders Eligible for Study: Both - Patient must be not eligible for conventional allogeneic hematopoietic cell transplantation (HCT) and must have disease expected to be stable for at least 100 days without chemotherapy; patients with hematologic malignancies treatable with HCT or with a B cell malignancy except those curable with autologous transplant will be included; patients not eligible for active disease specific protocols, may be enrolled in this protocol - Diffuse large B cell non-Hodgkin lymphoma (NHL) and other aggressive Lymphomas not eligible for conventional myeloablative HCT or after autologous HCT - Low grade NHL- with < 6 months duration of complete response (CR) between courses of conventional therapy - Mantle cell NHL- may be treated in first CR - Chronic lymphocytic leukemia (CLL)- must have either - 1) failed to meet NCI Working Group criteria for complete or partial response after therapy with a regimen containing FLU (or another nucleoside analog, e.g. 2-CDA, pentostatin) or experience disease relapse within 12 months after completing therapy with a regimen containing FLU (or another nucleoside analog); - 2) failed FLU-CY-Rituximab (FCR) combination chemotherapy at any time point; or - 3) have "17p deletion" cytogenetic abnormality; patients should have received induction chemotherapy but could be transplanted in 1st CR - 4) patients with a diagnosis of CLL (or small lymphocytic lymphoma) or a diagnosis of CLL that progresses to prolymphocytic leukemia (PLL), to T-cell CLL or PLL - Hodgkin Lymphoma (HL)- must have received and failed frontline therapy; patients must have failed or were not eligible for autologous transplant - Multiple myeloma (MM)- following a planned autologous transplant or equivalent high-dose therapy without a graft, or following a failed prior autograft - Acute myeloid leukemia (AML)- must have < 5% marrow blasts at the time of transplant - Acute lymphoblastic leukemia (ALL)- must have < 5% marrow blasts at the time of transplant - Chronic myelogenous leukemia (CML)- patients will be accepted beyond CP1 if they have received previous myelosuppressive chemotherapy or HCT, and have < 5% marrow blasts at time of transplant - Myelodysplastic syndromes/myeloproliferative disorders (MDS/MPD)- must have received previous myelosuppressive chemotherapy or HCT and have < 5% marrow blasts at time of transplant - Waldenstrom's Macroglobulinemia- must have failed 2 courses of therapy - Myelosuppressive chemotherapy must be discontinued three weeks prior to conditioning with the exception of hydroxyurea or imatinib - Patients < 12 years old must be approved by both the participating institutions' patient review committee such as the Patient Care Conference (PCC) at the FHCRC and the FHCRC principal investigator - Patient who refused to be treated on a conventional HCT protocol; for this inclusion criterion, transplants must be approved by both the participating institution's patient review committee such as the Patient Care Conference (PCC) at the FHCRC and the FHCRC principal investigators - Patients with human leukocyte antigen (HLA)-matched related donors - Patients with renal failure are eligible; however, patients with renal compromise (serum creatinine > 2.0) will likely have further compromise in renal function and may require hemodialysis (which may be permanent) due to the need to maintain adequate serum tacrolimus levels - DONOR: Related donor who is HLA genotypically identical at least at one haplotype and may be phenotypically or genotypically identical at the allele level at HLA-A, -B, -C, -DRB1, and -DQB1 - DONOR: Donor must consent to G-CSF administration and leukapheresis - DONOR: Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral, subclavian) Other eligibility criteria may apply. - Eligible for a high priority curative autologous transplant - Patient with rapidly progressive, aggressive NHL unless in minimal disease state - Patients with chronic myelomonocytic leukemia (CMML) - Life expectancy severely limited by diseases other than malignancy - Any current central nervous system (CNS) involvement with disease refractory to intrathecal chemotherapy - Presence of circulating leukemic blasts (in the peripheral blood) detected by standard pathology for patients with AML, ALL or CML - Fertile men or women unwilling to use contraceptives during and for up to 12 months post treatment - Female patients who are pregnant or breastfeeding - Human immunodeficiency virus (HIV)-positive patients - Patients with active non-hematologic malignancies (except non-melanoma skin cancers); this exclusion does not apply to patients with non-hematologic malignancies that do not require therapy - Patients with a history of non-hematologic malignancies (except non-melanoma skin cancers) currently in a complete remission, who are less than 5 years from the time of complete remission, and have a > 20% risk of disease recurrence; this exclusion does not apply to patients with non-hematologic malignancies that do not require therapy - Fungal pneumonia with radiological progression after receipt of amphotericin formulation or mold-active azoles for greater than 1 month - Karnofsky score < 50 for adult patients - Lansky-Play Performance Score < 50 for pediatric patients - Symptomatic coronary artery disease or ejection fraction < 35% or other cardiac failure requiring therapy (or, if unable to obtain ejection fraction, shortening fraction of < 26%); ejection fraction is required if age > 50 years or there is a history of anthracycline exposure or history of cardiac disease; patients with a shortening fraction < 26% may be enrolled if approved by a cardiologist - Poorly controlled hypertension - Diffusing capacity of the lung for carbon monoxide (DLCO) < 30%, total lung capacity (TLC) < 30%, forced expiratory volume in one second (FEV1) < 30% and/or receiving supplementary continuous oxygen; the FHCRC PI of the study must approve enrollment of all patients with pulmonary nodules - Liver function abnormalities: Patients with clinical or laboratory evidence of liver disease would be evaluated for the cause of liver disease, its clinical severity in terms of liver function, and the degree of portal hypertension; patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension or bridging fibrosis, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, and symptomatic biliary disease - Patients with active bacterial or fungal infections unresponsive to medical therapy - DONOR: Age less than 12 years - DONOR: Identical twin - DONOR: Pregnancy - DONOR: Infection with HIV - DONOR: Known allergy to filgrastim (G-CSF) - DONOR: Current serious systemic illness that would result in increased risk for G-CSF mobilization and harvest of peripheral blood stem cells (PBSC) Other exclusion criteria may apply. 8e6a164ac05fcc0a7e4325e58b254664 6288 Umbilical Cord Blood Transplant, Cyclophosphamide, Fludarabine Phosphate, and Total-Body Irradiation in Treating Patients With Hematologic Disease II Colleen Delaney, MD, MSc 2010.00 1; 2; 3; 11; 15; 19; 36; 38; 43; 48; 55; 57; 61; 64; 121 Acute Lymphoid Leukemia (ALL); Acute Myeloid Leukemia (AML); Acute Promyeloid Leukemia (APL); Bone Marrow and Hematopoietic Stem Cell Transplant (BMT and HSCT); Burkitt's Lymphoma; Chronic Myeloid Leukemia (CML); Hematologic Malignancies; Hodgkin's Lymphoma; Leukemia; Lymphoma; Childhood Cancers, Miscellaneous; Multiple Myeloma (MM); Myelodysplastic and Myeloproliferative Syndromes (MDS and MPD); Non-Hodgkin's Lymphoma (NHL); Umbilical Cord Blood Transplant (UCBT) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.6288.html http://www.clinicaltrials.gov/ct/search?term=NCT00719888 NCT00719888 Purpose: This phase II trial studies how well giving an umbilical cord blood transplant together with cyclophosphamide (CY), fludarabine phosphate (FLU), and total-body irradiation (TBI) works in treating patients with hematologic disease. Giving chemotherapy, such as CY and FLU, and TBI before a donor umbilical cord blood transplant helps stop the growth of cancer and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after transplant may stop this from happening. Ages Eligible for Study: 6 Months to 45 Years Genders Eligible for Study: Both Inclusion Criteria: *GRAFT CRITERIA: -- UCB units will be selected according to current umbilical cord blood graft selection algorithm; one or 2 UCB units may be used to achieve the required cell dose -- The UCB graft is matched at 4-6 human leukocyte antigen (HLA)-A, B, DRB1 antigens with the recipient; this may include 0-2 antigen mismatches at the A or B or DRB1 loci; unit selection based on cryopreserved nucleated cell dose and HLA-A,B, DRB1 using intermediate resolution A, B antigen and DRB1 allele typing -- If 2 UCB units are required to reach the target cell dose, each unit must be a 4-6 antigen match to the recipient *Acute myeloid leukemia (AML): -- High risk first complete remission (CR1) as evidenced by preceding myelodysplastic syndromes (MDS), high risk cytogenetics (for example, monosomy 5 or 7), or high risk as defined by referring institution treatment protocol, >= 2 cycles to obtain complete response (CR), erythroblastic or megakaryocytic leukemia; >= second complete remission (CR2) -- All patients must be in CR as defined by hematologic recovery and < 5% blasts by morphology within the bone marrow and a cellularity of >= 15% -- Patients in which adequate marrow/biopsy specimens cannot be obtained to determine remission status by morphologic assessment, but have fulfilled criteria of remission by flow cytometry, recovery of peripheral blood counts with no circulating blasts, and/or normal cytogenetics (if applicable) may still be eligible; reasonable attempts must be made to obtain an adequate specimen for morphologic assessment, including possible repeat procedures - Very high risk pediatric/young adult patients with AML: Patients < 25 years, however, are eligible with (M2 marrow) with =< 25% blasts in marrow after having failed one or more cycles of chemotherapy; this group of patients will be analyzed separately *Acute Lymphoblastic Leukemia (ALL): -- High risk CR1 [for example, but not limited to: t(9;22), t(1;19), t(4;11) or other mixed lineage leukemia (MLL) rearrangements, hypodiploid] -- Greater than 1 cycle to obtain CR -- >= CR2 -- All patients must be in CR as defined by hematologic recovery and < 5% blasts by morphology within the bone marrow and a cellularity of >= 15% -- Patients in which adequate marrow/biopsy specimens cannot be obtained to determine remission status by morphologic assessment, but have fulfilled criteria of remission by flow cytometry, recovery of peripheral blood counts with no circulating blasts, and/or normal cytogenetics (if applicable) may still be eligible; reasonable attempts must be made to obtain an adequate specimen for morphologic assessment, including possible repeat procedures - Chronic myelogenous leukemia (CML) excluding refractory blast crisis; to be eligible in first chronic phase (CP1) patient must have failed or be intolerant to imatinib mesylate - Advanced myelofibrosis - Myelodysplasia (MDS) International Prognostic Scoring System (IPSS) Int-2 or High risk (i.e., refractory anemia with excess blasts [RAEB], RAEB in transformation [RAEBt]) or refractory anemia with severe pancytopenia or high risk cytogenetics; blasts must be < 10% by a representative bone marrow aspirate morphology - Lymphoblastic lymphoma, Burkitt's lymphoma, and other high-grade NHL after initial therapy if stage III/IV in first partial response (PR1) or after progression if stage I/II < 1 year; stage III/IV patients are eligible after progression in CR/PR - Chronic lymphocytic leukemia /small lymphocytic lymphoma (CLL/SLL), marginal zone B-cell lymphoma, lymphoplasmacytic lymphoma or follicular lymphoma that have progressed after at least two different prior therapies; patients with bulky disease (nodal mass greater than 5 cm) should be considered for debulking chemotherapy before transplant; these patients must be presented at primary care center (PCC) prior to enrollment, given potential competing eligibility on autotransplant protocols *Mantle-cell lymphoma, prolymphocytic leukemia: -- Eligible after initial therapy in >= CR1 or >= PR1 *Large cell Non-Hodgkin lymphoma (NHL): -- Patients in CR2/second partial response (PR2) with initial short remission (< 6 months) are eligible -- These patients must be presented at PCC prior to enrollment, given potential competing eligibility on autotransplant protocols - Multiple myeloma beyond PR2: Patients with chromosome 13 abnormalities, first response lasting less than 6 months, or beta-2 microglobulin > 3 mg/L, may be considered for this protocol after initial therapy - Performance status score: Karnofsky (for adults) >= 70% or Lansky (for children) >= 50% - Creatinine < 2.0 mg/dL (for adults) or creatinine clearance > 60 ml/min (for children) - Patients with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, histology, and the degree of portal hypertension; patients with fulminant liver failure, cirrhosis with evidence of portal hypertension or bridging fibrosis, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, or correctable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3mg/dL, and symptomatic biliary disease will be excluded - Diffusion capacity for carbon monoxide corrected (DLCOcorr) > 50% normal - Left ventricular ejection fraction > 45% or shortening fraction > 26% Other eligibility criteria may apply. Exclusion Criteria: - Uncontrolled viral or bacterial infection at the time of study enrollment - Active or recent (prior 6 month) invasive fungal infection without interdisciplinary (ID) consult and approval - History of human immunodeficiency virus (HIV) infection - Pregnant or breastfeeding - Chemotherapy refractory large cell and high grade NHL (i.e., progressive disease after > 2 salvage regimens) - Prior myeloablative transplant containing full dose TBI (greater than 8 Gray [Gy]) - Any prior myeloablative transplant within the last 6 months - Extensive prior therapy including > 12 months alkylator therapy or > 6 months alkylator therapy with extensive radiation - Patients who have received Y-90 ibritumomab (Zevalin) or I-131 tositumomab (Bexxar), as part of their salvage therapy are not eligible for myeloablative umbilical cord blood transplant Other exclusion criteria may apply. a4f992a3c5f0b01ec544efb427de2c57 6459 A Pilot Study to Evaluate the Co-Infusion of Ex Vivo Expanded Cord Blood Cells With an Unmanipulated Cord Blood Unit in Patients Undergoing Cord Blood Transplant for Hematologic Malignancies I Colleen Delaney, MD, MSc 2044.00 1; 2; 3; 11; 15; 19; 36; 38; 43; 48; 55; 57; 61; 64; 121 Acute Lymphoid Leukemia (ALL); Acute Myeloid Leukemia (AML); Acute Promyeloid Leukemia (APL); Bone Marrow and Hematopoietic Stem Cell Transplant (BMT and HSCT); Burkitt's Lymphoma; Chronic Myeloid Leukemia (CML); Hematologic Malignancies; Hodgkin's Lymphoma; Leukemia; Lymphoma; Childhood Cancers, Miscellaneous; Multiple Myeloma (MM); Myelodysplastic and Myeloproliferative Syndromes (MDS and MPD); Non-Hodgkin's Lymphoma (NHL); Umbilical Cord Blood Transplant (UCBT) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/about/pubs/center_news/2005/may19/sart1.html http://www.fhcrc.org/en/treatment/clinical-trials/detail.6459.html http://www.clinicaltrials.gov/ct/search?term=NCT00343798 NCT00343798 For some patients with hematologic malignancies, the best chance for survival or cure may be a bone-marrow transplant, yet many of these patients cannot find a suitable blood-stem-cell donor (either a "matched" relative or an unrelated donor). This is particularly true for minority patients and patients of mixed ethnicity. For those patients who do not have a suitable donor, umbilical cord blood can be used as an alternative source of blood stem cells for bone-marrow transplant. However, the use of cord blood is relatively new and is still considered to be an alternative type of transplant. Furthermore, the use of cord blood for bone-marrow transplant is limited in adults and larger children due to the low number of cells available in a single cord blood unit. The purpose of this study is to evaluate the safety of giving study participants umbilical-cord-blood cells that have been grown (expanded) in the laboratory to increase the number of cells available for the transplant. In the case of this study, two separate, unrelated umbilical-cord-blood units are used - one unit that has been expanded in the lab to increase the number of cells, and one that has not been expanded or manipulated in any way. This second, unmanipulated unit of cord-blood cells is given as a measure of safety, to ensure that the participant will receive adequate numbers of cells. Giving the expanded cells to study participants is experimental, and the safety of this treatment has not yet been determined. Participants will be hospitalized for the transplant. Adult participants will be hospitalized in Seattle at the University of Washington Medical Center, and pediatric participants at the Children’s Hospital and Regional Medical Center. Once discharged from the hospital, care will be given at the Seattle Cancer Care Alliance (SCCA) outpatient clinic. The participant will be discharged from the hospital when medically ready. It will be necessary to return for follow-up to the clinic frequently initially (1-3 times per week), and subsequently at specific dates as determined by the participant’s physician. Follow-up care after transplantation (after about three months) will be according to the participant’s specific type of disease. Physical exams and tests will likely occur at 3 and 6 months, 1 year, and 2 years after the transplantation. We may request that additional bone marrow or blood samples be drawn at various time points for up to 5 years after the transplant. 1. Participant is between the ages of 6 months and 45 years of age. 2. Participant does not have a suitably-matched, related or unrelated donor. 3. Participant has adequate heart, lung, kidney and liver function. 4. Participant has one of the following diseases: a. Acute leukemia in complete remission (high risk CR1 or subsequent CR); b. Chronic myelogenous leukemia (except refractory blast crisis); c. Myelodysplastic syndrome (MDS) with severe pancytopenia or complex cytogenetics; d. Large-cell lymphoma, Hodgkin’s lymphoma, multiple myeloma, chronic lymphocytic leukemia/small lymphocytic lymphoma, marginal zone b-cell lymphoma, follicular lymphoma, lymphoplasmacytic lymphoma, mantle-cell lymphoma, and prolymphocytic leukemia may be eligible according to study guidelines. e. Refractory leukemia or MDS in aplasia after chemotherapy or radiolabeled antibody. Other eligibility criteria may apply. 1. A suitable donor is available (5-6/6 HLA-A, B, DRB1 matched sibling donor). 2. Pregnancy or breastfeeding. 3. Evidence of HIV infection. 4. Uncontrolled viral, or bacterial infection at the time of study enrollment. 5. Active or recent (prior 6 months) invasive fungal infection without ID consult and approval. 6. Presence of acute leukemia that has returned or is persistent. 7. Presence of chronic myelogenous leukemia (CML) in refractory blast crisis. 8. Presence of large-cell lymphoma, mantle-cell lymphoma and Hodgkin’s lymphoma that is progressive on salvage therapy. Stable disease is acceptable to move forward provided it is non-bulky. Other exclusion criteria may apply. 2a9aa8318cdb35a1b1f537831b25d2f4 7076 Iodine I 131 Monoclonal Antibody BC8, Fludarabine Phosphate, Cyclophosphamide, Total-Body Irradiation and Donor Bone Marrow Transplant in Treating Patients With Advanced Acute Myeloid Leukemia or Acute Lymphoblastic Leukemia or High-Risk Myelodysplastic Syndrome II John Pagel, MD, PhD 2186.00 1; 2; 11; 36; 43; 61 Acute Lymphoid Leukemia (ALL); Acute Myeloid Leukemia (AML); Bone Marrow and Hematopoietic Stem Cell Transplant (BMT and HSCT); Hematologic Malignancies; Leukemia; Myelodysplastic and Myeloproliferative Syndromes (MDS and MPD) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.7076.html http://www.clinicaltrials.gov/ct/search?term=NCT00589316 NCT00589316 The purpose of this study is to learn more about an experimental, two-part treatment for patients with advanced acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or high-risk myelodysplastic syndrome (MDS). This study will look at the effects, good or bad, that this combined treatment has on the body and leukemia or MDS. The study will also help us determine the highest dose of radiation we can give safely. The two parts of the treatment are: • targeted radiolabeled antibody therapy, followed by • bone marrow transplant from a related, mismatched donor The type of bone marrow transplant in this study has been used before to treat leukemia, MDS and other similar diseases. It has been effective in getting the donor’s stem cells to “take hold” in the recipient, but many patients relapse (the disease returns) after transplant. We want to find out if using the radiolabeled antibody before the transplant will reduce the number of patients who relapse after transplant. Participants will receive treatment as outpatients at the Seattle Cancer Care Alliance (SCCA) and as inpatients at the University of Washington Medical Center (UWMC). The radiation used in the study requires participants to stay in a “radiation isolation” room at UWMC for about 5 to 10 days. Participants in this study will need to be in Seattle for about 4 months. This includes about 3 weeks from the start of study participation until the bone marrow transplant, and then about 3 months of follow-up after the transplant. - 1) Males or females with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL) or myelodysplastic syndrome (MDS) - AML or ALL patients must have disease that has either: - a) come back after first remissi - b) did not respond to initial treatmtent OR - c) evolved from myelodysplastic or myeloproliferative syndrome - MDS patients must have one of the following: - a) refractory anemia with excess blasts (RAEB), - b) RAEB in transformation (RAEBT), - c) refractory cytopenia with multilineage dysplasia (RCMD), - d) RCMD with ringed sideroblasts (RCMD-RS OR - e) chronic myelomonocytic leukemia (CMML) - 2) . Must be 18 years of age or older - 3) Must have normal liver and kidney function - 4) Must be physically able to meet study requirements - 5) Must not have active infection - 6) Must have a related donor who meets study guidelines Other eligibility criteria may apply. - 1) Already received maximum radiation to any organ - 2) Severe heart problems requiring medication, or symptoms of coronary artery disease - 3) Severe lung or liver problems - 4) HIV positive - 5) Medical or other condition that may prevent the patient from finishing the study - 6) Pregnant or breast feeding Other exclusion criteria may apply. 476303542c8996481f823f1893dc2df2 8478 Sirolimus, Cyclosporine, and Mycophenolate Mofetil In Preventing Graft-Versus-Host Disease in Treating Patients With Hematologic Malignancies Undergoing Donor Peripheral Blood Stem Cell Transplant II Brenda Sandmaier, MD 2206.00 11; 36; 43; 48; 57; 61 Bone Marrow and Hematopoietic Stem Cell Transplant (BMT and HSCT); Hematologic Malignancies; Leukemia; Lymphoma; Multiple Myeloma (MM); Myelodysplastic and Myeloproliferative Syndromes (MDS and MPD) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8478.html http://www.clinicaltrials.gov/ct/search?term=NCT01251575 NCT01251575 This phase II trial studies how well giving sirolimus together with cyclosporine and mycophenolate mofetil works in preventing graft-vs-host disease (GVHD) in patients with hematologic malignancies undergoing donor peripheral blood stem cell (PBSC) transplant. Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving total-body irradiation together with sirolimus, cyclosporine, and mycophenolate mofetil before and after transplant may stop this from happening Genders Eligible for Study: Both - Ages > 50 years with hematologic malignancies treatable by related or unrelated HCT - Ages =< 50 years of age with hematologic diseases treatable by allogeneic HCT who through pre-existing medical conditions or prior therapy are considered to be at high risk for regimen related toxicity associated with a high dose transplant (> 40% risk of transplant-related mortality [TRM]); this criterion can include patients with a HCT-comorbidity index (CI) score of >= 1; transplants should be approved for these inclusion criteria by both the participating institutions' patient review committees such as the Patient Care Conference (PCC) at the Fred Hutchinson Cancer Research Center (FHCRC) and by the principal investigators at the collaborating centers; patients =< 50 years of age who have received previous high-dose transplantation do not require patient review committee approvals; all children < 12 years must be discussed with the FHCRC Principal Investigator (PI) prior to registration - Ages =< 50 years of age with chronic lymphocytic leukemia (CLL) (these patients do not require patient review committee approvals) - Ages =< 50 years of age with hematologic diseases treatable by allogeneic HCT who refuse a high-dose HCT; transplants must be approved for these inclusion criteria by both the participating institutions' patient review committee such as PCC at the FHCRC and by the principal investigators at the collaborating centers - Aggressive non-Hodgkin lymphomas (NHL) and other histologies such as diffuse large B cell NHL: not eligible for autologous HCT, not eligible for high-dose allogeneic HCT, or after failed autologous HCT - Mantle Cell NHL: may be treated in first complete remission (CR); (diagnostic LP required pre-transplant) - Low grade NHL: with < 6 month duration of CR between courses of conventional therapy - CLL: must have either: --- 1) failed to meet National Cancer Institute (NCI) Working Group criteria for complete or partial response after therapy with a regimen containing FLU (or another nucleoside analog, e.g. 2-CDA, pentostatin) or experience disease relapse within 12 months after completing therapy with a regimen containing fludarabine (FLU) (or another nucleoside analog); OR --- 2) failed FLU-cyclophosphamide (CY)-Rituximab (FCR) combination chemotherapy at any time point; OR --- 3) have "17p deletion" cytogenetic abnormality; patients should have received induction chemotherapy but could be transplanted in 1st CR; --- 4) patients with a diagnosis of CLL (or small lymphocytic lymphoma) that progresses to prolymphocytic leukemia (PLL); OR --- 5) patients with T-cell CLL or PLL - Hodgkin Lymphoma: must have received and failed frontline therapy - Multiple Myeloma: must have received prior chemotherapy; consolidation of chemotherapy by autografting prior to nonmyeloablative HCT is permitted - Acute Myeloid Leukemia (AML): must have < 5% marrow blasts at the time of transplant - Acute Lymphocytic Leukemia (ALL): must have < 5% marrow blasts at the time of transplant - Chronic Myeloid Leukemia (CML): patients in chronic phase 1 (CP1) must have failed or be intolerant of tyrosine kinase inhibitors (TKIs); patients beyond CP1 will be accepted if they have < 5% marrow blasts at time of transplant - Myelodysplasia(MDS)/Myeloproliferative Syndrome (MPS): Patients must have < 5% marrow blasts at time of transplant - Waldenstrom's Macroglobulinemia: must have failed 2 courses of therapy - Patients with related or unrelated donors for whom the best available donor is: -- a) Mismatched at antigen level for any single class I locus (HLA-A, -B, -C) +/- an additional class I mismatch at the allele level OR mismatched at the allele level for any 2 class I loci (if typed at the molecular level) OR mismatched at the antigen or allele level for class II loci HLA-DRB1 and/or - DQB1; must be matched for at least one DRB1 allele and one DQB1 allele; -- b) there is a likelihood of rapid disease progression while HLA typing and results of a preliminary search and the donor pool suggests that a 10/10 HLA-A, B, C, DRB1 and DQB1 matched donor will not be found; c) there is no HLA-A, -B or -C one locus allelic mismatched donor available - DONOR: Related or unrelated volunteer donors who are mismatched with the recipient within one of the following limitations: --- Mismatch for one HLA class I antigen with or without an additional mismatch for one HLA-class I allele, but matched for HLA-DRB1 and HLA-DQ, OR --- Mismatched for two HLA class I alleles, but matched for HLA-DRB1 and HLA-DQ, OR --- Mismatched for one HLA-DRB1 antigen or allele with or without an additional mismatch for HLA-DQ, but matched for HLA-class I alleles - DONOR: HLA-matching must be based on results of high resolution typing at HLA-A, -B, -C, -DRB1, and -DQB - DONOR: Two mismatches at a single HLA- locus is not allowed - DONOR: Donors are excluded when preexisting immunoreactivity is identified that would jeopardize donor hematopoietic cell engraftment; this determination is based on the standard practice of the individual institution; the donor should be excluded if any of the flow cytometric B and T cell cytotoxic cross match assays are positive - DONOR: Only filgrastim (G-CSF) mobilized PBSC only will be permitted as a hematopoietic stem cell (HSC) source on this protocol Other eligibility criteria may apply. - Patients who are homozygous at the mismatched major histocompatibility complex (MHC) class I locus or II locus - Patients for whom the best available donor is mismatched at both HLA class I and class II - A positive cross-match exists between the donor and recipient - Patients with rapidly progressive intermediate or high grade NHL - Patients with a diagnosis of chronic myelomonocytic leukemia (CMML) - Patients with refractory anemia with excess blasts (RAEB) who have not received myelosuppressive chemotherapy i.e. induction chemotherapy - Presence of circulating leukemic blasts (in the peripheral blood) detected by standard pathology for patients with AML, MDS, ALL or CML - Central nervous system (CNS) involvement with disease refractory to intrathecal chemotherapy - Fertile men or women unwilling to use contraceptives during and for up to 12 months following treatment - Female patients who are pregnant or breast-feeding - Human immunodeficiency virus (HIV) positive patients - Patients with active non-hematologic malignancies (except non-melanoma skin cancers) or those with non-hematologic malignancies (except non-melanoma skin cancers) who have been rendered with no evidence of disease, but have a greater than 20% chance of having disease recurrence within 5 years; this exclusion does not apply to patients with non-hematologic malignancies that do not require therapy - Fungal infections with radiological progression after receipt of amphotericin B or active triazole for greater than 1 month - Patients with active bacterial or fungal infections unresponsive to medical therapy - Cardiac ejection fraction < 35% (or, if unable to obtain ejection fraction, shortening fraction of < 26%); ejection fraction is required if the patient is > 50 years of age, or history of cardiac disease or anthracycline exposure; patients with a shortening fraction < 26% may be enrolled if approved by a cardiologist - Corrected diffusion capacity of carbon monoxide (DLCO) < 40%, total lung capacity (TLC) < 40%, forced expiratory volume in one second (FEV1) < 40% and/or receiving supplementary continuous oxygen - The FHCRC PI of the study must approve of enrollment of all patients with pulmonary nodules - Patients with clinical or laboratory evidence of liver disease would be evaluated for the cause of liver disease, its clinical severity in terms of liver function, and the degree of portal hypertension; patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bridging fibrosis, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, or symptomatic biliary disease - Patients with poorly controlled hypertension on multiple antihypertensives - Karnofsky scores < 60 or Lansky Score < 50 - All patients receiving antifungal therapy voriconazole, posaconazole, or fluconazole must have sirolimus reduced according to the Standard Practice Antifungal Therapy Guidelines - The addition of cytotoxic agents for "cytoreduction" with the exception of tyrosine kinase inhibitors (such as imatinib), cytokine therapy, hydroxyurea, low dose cytarabine, chlorambucil, or rituxan will not be allowed within three weeks of the initiation of conditioning - DONOR: Donor (or centers) who will exclusively donate marrow - DONOR: Donors who are HIV-positive and/or, medical conditions that would result in increased risk for G-CSF mobilization and harvest of PBSC Other exclusion criteria may apply. babb72e7e8d86db47b0b19b36a42703d 7575 Immune Response After Stem Cell Transplant in HIV-Positive Patients With Hematologic Cancer II Ann Woolfrey, MD 2212.00 11; 36; 39 Bone Marrow and Hematopoietic Stem Cell Transplant (BMT and HSCT); Hematologic Malignancies; Immunodeficiency Syndromes Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.7575.html http://www.clinicaltrials.gov/ct/search?term=NCT00968630 NCT00968630 This phase II trial studies the immune response after stem cell transplant in human immunodeficiency virus (HIV)-positive patients with hematologic cancer. Studying samples of blood from HIV-positive patients with cancer in the laboratory may help doctors learn more about changes that occur in the immune system after stem cell transplant. Ages Eligible for Study: up to 75 Years Genders Eligible for Study: Both - HIV positive - Treatment with HAART for at least 1 month - Viral load has decreased by >= 1.5 logs or viral load < 5000 copies/ml plasma on HAART therapy - Hematologic malignancy associated with a poor prognosis with medical therapy alone - diagnoses to be included: - 1) Acute Myeloid Leukemia in first remission, second remission, or relapse - 2) Acute Lymphoblastic Leukemia in first remission, second remission, or relapse - 3) Chronic Myeloid Leukemia in accelerated phase or blast phase. Chronic phase is allowed if patient has not achieved a cytogenetic remission or has developed unacceptable toxicity to medical therapy, such as tyrosine kinase inhibitor therapy - 4) Myelodysplastic syndrome (MDS) with International Prognostic Scoring System (IPSS) score > 1 - 5) Myeloproliferative disorders, including Chronic Myelomonocytic Leukemia (CMML), Agnogenic Myeloid Metaplasia with Myelofibrosis, Juvenile CML, or unclassified myeloproliferative disorders - 6) Hodgkin's Lymphoma beyond first remission; first remission allowed if approved by Patient Care Conference - 7) Non-Hodgkin Lymphoma beyond first remission; first remission allowed if approved by Patient Care Conference - Approval for allogenic regimen given at Patient Care Conference - Additional inclusion criteria may apply if the patient is also enrolled on a Primary Research Protocol; please refer to the Primary Research Protocol for additional required inclusion criteria; eligibility criteria for patients enrolled at other institutions may be determined by the Institutional Primary Research protocol in lieu of criteria listed above - DONOR: Autologous peripheral blood with CD34+ cell dose of > 3.0 x 10^6 cells per kilogram recipient weight; autologous recipients are allowed to proceed to nonmyeloablative allogeneic HCT on protocol 1410 - DONOR: Related donor matched for at least 9 of 10 human leukocyte antigen (HLA)-A, B, C, DRB1, and DQB1 alleles - DONOR: Unrelated donor matched for at least 9 of 10 HLA-A, B, C, DRB1, and DQB1 alleles and willing to donate either marrow or peripheral blood stem cells; the acceptable level of the single mismatch is defined as an allele level mismatch at HLA-DRB1 or an antigen level mismatch at HLA-A, B, C, or DQB1 - DONOR: Donor inclusion criteria may be expanded in the case where the patient is also enrolled on a separate Institutional Review Board (IRB)-approved Primary Research Protocol; please refer to the Primary Research Protocol for Donor Inclusion Criteria Other eligibility criteria may apply. - Positive serology for toxoplasma gondii AND requiring treatment or with evidence of active infection - A medical history of noncompliance with HAART or medical therapy - Serum creatinine > 2 times upper limit of normal (ULN) - Serum bilirubin greater than 3 times the ULN unless determined to be a result of the primary hematologic malignancy or attributed to Gilbert's Syndrome - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) greater than 3 times the ULN, unless determined to be a result of the primary hematologic malignancy or attributed to Gilbert's Syndrome - Forced vital capacity (FVC), forced expiratory volume (FEV)1 or diffusing capacity of the lung for carbon monoxide (DLCO) parameters < 60% predicted (corrected for hemoglobin) - Cardiac insufficiency or coronary artery disease requiring treatment - Active infection requiring systemic antibiotic therapy with antibacterial, antifungal, or antiviral agents (excluding HIV) - Karnofsky performance score < 70 - Cardiac insufficiency or coronary artery disease requiring treatment - Active infection requiring systemic antibiotic therapy with antibacterial, antifungal, or antiviral agents (excluding HIV) - Karnofsky performance score < 70 - Patients capable of conceiving a child and unwilling to use procedures to prevent conception - Pregnancy or patients actively breastfeeding - Additional exclusion criteria may apply if the patient is also enrolled on a Primary Research Protocol; please refer to the Primary Research Protocol for additional exclusion criteria - DONOR: HIV positive - DONOR: Medical or psychological reason that would make donor procedure intolerable - DONOR: Age > 75 years - DONOR: Medical history, physical exam, or laboratory findings that indicate donation would entail excess risk to donor or patient; this includes, but is not limited to pregnancy, history of autoimmune disorder, thromboembolism, serious adverse reaction to anesthesia, current treatment with lithium or monoclonal antibodies or any experimental drug, laboratory findings of hemoglobinopathy, thrombocytopenia, or blood borne pathogens; any unrelated donor must have approval by the Donor Center after evaluation by history and physical Other exclusion criteria may apply. 55b4d97b7eab3997da7a5cfa50a37cbd 7340 Fludarabine Phosphate, Cyclophosphamide, Total-Body Irradiation, and Donor Bone Marrow Transplant Followed by Donor Natural Killer Cell Therapy, Mycophenolate Mofetil, and Tacrolimus in Treating Patients With Hematologic Cancer II Brenda Sandmaier, MD 2230.00 1; 2; 11; 18; 19; 36; 38; 43; 48; 57; 61; 64 Acute Lymphoid Leukemia (ALL); Acute Myeloid Leukemia (AML); Bone Marrow and Hematopoietic Stem Cell Transplant (BMT and HSCT); Chronic Lymphoid Leukemia (CLL); Chronic Myeloid Leukemia (CML); Hematologic Malignancies; Hodgkin's Lymphoma; Leukemia; Lymphoma; Multiple Myeloma (MM); Myelodysplastic and Myeloproliferative Syndromes (MDS and MPD); Non-Hodgkin's Lymphoma (NHL) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.7340.html http://www.clinicaltrials.gov/ct/search?term=NCT00789776 NCT00789776 Purpose: This phase I/II trial is studying the side effects and best dose of donor natural killer (NK) cell therapy and to see how well it works when given together with fludarabine phosphate, cyclophosphamide, total-body irradiation, donor bone marrow transplant, mycophenolate mofetil, and tacrolimus in treating patients with hematologic cancer. Giving chemotherapy, such as fludarabine phosphate and cyclophosphamide, and total-body irradiation before a donor bone marrow transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Giving an infusion of the donor's T cells (donor lymphocyte infusion) may help the patient's immune system see any remaining cancer cells as not belonging in the patient's body and destroy them (called graft-versus-tumor effect). Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving mycophenolate mofetil and tacrolimus after the transplant may stop this from happening. Genders Eligible for Study: Both - Patients with the following hematologic malignancies will be permitted although other diagnoses can be considered if approved by Patient Care Conference (PCC) and the principal investigators: -- Aggressive non-Hodgkin Lymphomas (NHL) and other histologies such as Diffuse Large B cell (DLBC) NHL - * a) not eligible for autologous HCT, - * b) not eligible for high-dose HCT, - * c) after failed autologous HCT, or - * d) be part of a tandem auto-allo approach for high risk patients -- Mantle Cell NHL must be beyond first complete response (CR) -- Low-grade NHL with < 6 month duration of CR between courses of conventional therapy - Chronic lymphocytic leukemia (CLL) must have either: -- 1) Failed to meet National Cancer Institute (NCI) Working Group criteria for complete or partial response after therapy with a regimen containing FLU (fludarabine phosphate) (or another nucleoside analog, e.g. 2-Chlorodeoxyadenosine [2-CDA], pentostatin) or experience disease relapse within 12 months after completing therapy with a regimen containing FLU (or another nucleoside analog) -- 2) Failed FLU- CY (cyclophosphamide)-Rituximab (FCR) combination chemotherapy at any time point; or -- 3) Have "17p deletion" cytogenetic abnormality and relapsed at any time point after any initial chemotherapy - Hodgkin Lymphoma - must have received and - * a) failed frontline therapy, - * b) not be eligible for autologous HCT, or - * c) or be part of a tandem auto-allo approach for high risk patients - Multiple Myeloma must have received more than one line of prior chemotherapy; consolidation of chemotherapy by autografting prior to nonmyeloablative HCT is permitted - Acute Myeloid Leukemia (AML) must have < 5% marrow blasts at the time of HCT - Acute Lymphocytic Leukemia (ALL) must have < 5% marrow blasts at the time of HCT - Chronic Myeloid Leukemia (CML) accepted if they are beyond chronic phase (CP)1 and if they have received previous myelosuppressive chemotherapy or HCT and have < 5% marrow blasts at time of transplant - Myelodysplasia (MDS)/Myeloproliferative Syndrome (MPS) - ( > intermediate 1 (int-1) per International Prognostic Scoring System [IPSS]) after > or = 1 prior cycle of induction chemotherapy; must have < 5% marrow blasts at time of transplant - Waldenstrom's Macroglobulinemia must have failed 2 courses of therapy - Patients must be expected to have disease controlled for at least 60 days after HCT - Patients for whom HLA-matched unrelated donor search could not be initiated or completed due to insurance reasons, concerns of rapidly progressive disease, and/or discretion of attending physician are eligible for this protocol - DONOR: Related, HLA-haploidentical donors who are identical for one HLA haplotype and mismatched for any number of HLA-A, -B, -C, DRB1 or DQB1 loci of the unshared haplotype - DONOR: Marrow will be the only allowed hematopoietic stem cell source - DONOR: Haploidentical donor selection will be based on standard institutional criteria, otherwise no specific prioritization will be made amongst the suitable available donors; donors will not be selected based on killer cell immunoglobulin-like receptor (KIR) status Other eligibility criteria may apply. - Patients with available HLA-matched related donors - Patients eligible for a curative autologous HCT - Significant organ dysfunction that would prevent compliance with conditioning, GHVD prophylaxis, or would severely limit the probability of survival: -- 1) Symptomatic coronary artery disease or ejection fraction < 35% or other cardiac failure requiring therapy (or, if unable to obtain ejection fraction, shortening fraction of < 26%); if shortening fraction is < 26% a cardiology consult is required with the principal investigator (PI) having final approval of eligibility -- 2) Diffusion capacity of the lung for carbon monoxide (DLCO) < 40% total lung capacity (TLC) < 40%, forced expiratory volume in one second (FEV1) < 40% and/or receiving supplementary continuous oxygen; the Fred Hutchinson Cancer Research Center (FHCRC) study PI must approve enrollment of all patients with pulmonary nodules -- 3) Liver function abnormalities: patient with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, bridging fibrosis, and the degree of portal hypertension; the patient will be excluded if he/she is found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3mg/dL, or symptomatic biliary disease - Human immunodeficiency virus (HIV) seropositive patients - Patients with poorly controlled hypertension despite multiple antihypertensive medications - Fertile females who are unwilling to use contraceptive techniques during and for the twelve months following treatment, as well as females who are pregnant or actively breast feeding - Fertile males who are unwilling to use contraceptive techniques during and for the twelve months following treatment - Patients with active non-hematologic malignancies (except non-melanoma skin cancers) or those with non-hematologic malignancies (except non-melanoma skin cancers) who have been rendered with no evidence of disease, but have a greater than 20% chance of having disease recurrence within five years; this exclusion does not apply to patients with non-hematologic malignancies that do not require therapy - Active infectious disease concerns - Karnofsky performance score < 60 Lansky performance score < 60 - Life expectancy severely limited by diseases other than malignancy - Patients with a diagnosis of chronic myelomonocytic leukemia (CMML) - Central nervous system (CNS) involvement with disease refractory to intrathecal chemotherapy - Patients with AML, MDS, ALL, or CML must not have presence of circulating leukemic blasts detected by standard pathology - Patients with aggressive lymphomas (such as DLBC) must not have bulky, rapidly progressive disease immediately prior to HCT - Patients who have received a prior allogeneic HCT must have no active GVHD requiring immunosuppressive therapy for at least 21 days prior to start of conditioning - DONOR: Children less than 12 years of age. - DONOR: Children greater than or equal to 12 years of age who have not provided informed assent in the presence of a parent and an attending physician who is not a member of the recipient's care team - DONOR: Children greater than or equal to 12 years of age who have inadequate peripheral vein access to safely undergo apheresis - DONOR: Donors unable or unwilling to undergo marrow harvest for the initial HCT, storage of autologous blood prior to marrow harvest or apheresis one week after marrow harvest - DONOR: Donors who are not expected to meet the minimum target dose of marrow cells (1 x 10^8 nucleated cells/kg recipient ideal body weight [IBW]) for the initial HCT; the average nucleated cell content of harvested marrow is 22 x 10^6 nucleated cells/mL or 220 x 10^8 nucleated cells/Liter - DONOR: HIV-positive donors - DONOR: Donors who are cross-match positive with recipient Other exclusion criteria may apply. 3dad78a5eddedc8a36b5528517433f14 7505 Iodine I 131 Monoclonal Antibody BC8 Before Autologous Stem Cell Transplant in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma or Non-Hodgkin I Ajay Gopal, MD 2238.00 11; 36; 48 Bone Marrow and Hematopoietic Stem Cell Transplant (BMT and HSCT); Hematologic Malignancies; Lymphoma Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.7505.html http://www.clinicaltrials.gov/ct/search?term=NCT00860171 NCT00860171 Purpose This phase I trial is studying the side effects and best dose of iodine I 131 monoclonal antibody BC8 when given before autologous stem cell transplant in treating patients with relapsed or refractory Hodgkin lymphoma or non-Hodgkin lymphoma. Radiolabeled monoclonal antibodies, such as iodine I 131 monoclonal antibody BC8, can find cancer cells and carry cancer-killing substances to them without harming normal cells. Giving iodine I 131 monoclonal antibody BC8 before an autologous stem cell transplant may kill more cancer cells Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Patients must have a histologically confirmed diagnosis of B-NHL, T-NHL, or HL; CD45 antigen expression must be documented on tumor specimens in all cases except HL, in whom histologic demonstration of CD45+ cells adjacent to the Reed Sternberg cells is required - Patients must have received at least one prior standard systemic therapy with documented recurrent or refractory disease - Mantle cell lymphoma (MCL), T-NHL, or other high-risk malignancies may be enrolled/transplanted in complete remission (CR)/first partial remission (PR1) - Patients are preferred to have either a tumor mass amenable to core needle biopsy during the dosimetry phase, or a measurable tumor mass with at least one site of involvement measuring 2.0 cm in largest dimension on computed tomography (CT) imaging for purposes of planar and/or single-photon emission CT (SPECT)/CT tumor dosimetry (patients with disease that does not allow tumor dosimetry will be allowed on study since they still can contribute toward achieving the primary endpoint, but these patients will be given a lower priority over those with evaluable disease) - Patients must have normal renal function (creatinine [Cr] < 2.0) - Patients must have normal hepatic function (bilirubin < 1.5 mg/dL), with the exception of patients thought to have Gilbert's syndrome, who may have a total bilirubin above 1.5 mg/dL - All patients eligible for therapeutic study must have a minimum of >= 4 x10^6 CD34/kg autologous hematopoietic stem cells harvested and cryopreserved and divided into 2 aliquots of at least >= 2 x10^6 CD34/kg each; patients with a history of prior autologous hematopoietic cell transplant (HCT) are only required to have >= 2x10^6 CD34/kg stored - Patients must have an expected survival of > 60 days and must be free of major infection Other eligibility criteria may apply. - Circulating human anti-mouse antibody (HAMA), to be determined before each infusion - Systemic anti-lymphoma therapy given in the previous 30 days before the scheduled therapy dose with the exception of rituximab - Inability to understand or give an informed consent - Lymphoma involving the central nervous system - Other serious medical conditions considered to represent contraindications to bone marrow transplant (BMT) (e.g. abnormally decreased cardiac ejection fraction, diffusion capacity of the lung for carbon monoxide (DLCO) < 50% predicted, forced expiratory volume in one second (FEV1) < 70% predicted, acquired immune deficiency syndrome [AIDS], etc.) - Known human immunodeficiency virus (HIV) seropositivity - Pregnancy or breast feeding - Prior allogeneic bone marrow or stem cell transplant - Prior autologous bone marrow or stem cell transplant or prior radiation therapy (RT) > 20Gy to a critical organ within 1 year of enrollment - Presence of circulating lymphoma cells by morphology or flow cytometry (> 0.1%) at or near the time of peripheral blood stem cell (PBSC) collection if unpurged/unselected PBSC are to be used (patients with cryopreserved stem cells which are negative (=< 0.1% involved) by flow cytometry will also be considered eligible) - Southwest Oncology Group (SWOG) performance status >= 2.0 - Unable to perform self-care during radiation isolation - Expected survival if untreated less than 60 days Other exclusion criteria may apply. 8ad940024d79ba7a5ae32b23f846afd2 7293 Donor Umbilical Cord Blood Transplant in Treating Patients With Hematologic Cancer II Colleen Delaney, MD, MSc 2239.00 1; 2; 18; 19; 36; 38; 43; 48; 57; 61; 121 Acute Lymphoid Leukemia (ALL); Acute Myeloid Leukemia (AML); Chronic Lymphoid Leukemia (CLL); Chronic Myeloid Leukemia (CML); Hematologic Malignancies; Hodgkin's Lymphoma; Leukemia; Lymphoma; Multiple Myeloma (MM); Myelodysplastic and Myeloproliferative Syndromes (MDS and MPD); Umbilical Cord Blood Transplant (UCBT) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.7293.html http://www.clinicaltrials.gov/ct/search?term=NCT00723099 NCT00723099 This phase II trial is studying how well umbilical cord blood transplant from a donor works in treating patients with hematological cancer. Giving chemotherapy and total-body irradiation (TBI) before a donor umbilical cord blood transplant helps stop the growth of cancer and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from an unrelated donor, that do not exactly match the patient's blood, are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cell from a donor can make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil before and after transplant may stop this from happening Ages Eligible for Study: up to 70 Years Genders Eligible for Study: Both - Patients > 70 may be considered if Performance Status > 80% and Comorbidity Score < 3 - Adequate cardiac function defined as absence of decompensated congestive heart failure, or uncontrolled arrhythmia - AND - left ventricular ejection fraction >= 35% - OR - Fractional shortening > 22% - Adequate pulmonary function defined as diffusion capacity of carbon monoxide (DLCO) > 30% predicted, and absence of oxygen (O2) requirements - Adequate hepatic function - Patients with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, histology, and the degree of portal hypertension - Adequate renal function defined as creatinine =< 2.0 mg/dl (adults) or creatinine clearance > 40 ml/min (pediatrics) - All adults with a creatinine > 1.2 or a history of renal dysfunction must have estimated creatinine clearance > 40 ml/min - Performance status score: Karnofsky (for adults) >= 60; Lansky (for children) score >= 50 - If recent mold infection, e.g., Aspergillus, must be cleared by infectious disease - Second hematopoietic cell transplant: Must be >= 3 months after prior myeloablative transplant - Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia: Must have < 5% morphologic marrow blasts in an evaluable marrow (> 25% of normal cellularity for age) collected less than one month prior to start of conditioning; patients persistently aplastic for greater than one month since completing last chemotherapy are also eligible with the approval of the principal investigator (PI) or designee - Chronic myelogenous leukemia: All types, except refractory blast crisis; chronic phase patients must have failed or been intolerant to Gleevec or other tyrosine kinase inhibitors; at time of transplant, patients must have < 5% blasts in an evaluable marrow (> 25% of normal cellularity for age) by morphology within the bone marrow - Myelodysplastic syndrome (MDS): Any subtype; morphologic blasts must be less than 5% in an evaluable marrow (> 25% of normal cellularity for age); if blasts are 5% or more, patient requires induction chemotherapy pre-transplant to reduce blast count to =< 5%; patients who have a hypocellular marrow in the absence of excess blasts that is related to the underlying disease or as a result of treatment for MDS may also be eligible with the approval of the principal investigator (PI) or designee - Large-cell lymphoma and aggressive T-cell lymphoma: With chemotherapy sensitive disease that has failed autologous transplant or patients who are ineligible for an autologous transplant; chemotherapy sensitive disease is defined as >= 50% reduction in the size of the tumor with the chemotherapy regimen immediately preceding transplant - Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL): Must be refractory to fludarabine or fail to have a complete or partial response after therapy with a regimen containing fludarabine (or another nucleoside analog, e.g. cladribine [2-CDA], pentostatin) or experience disease relapse within 12 months after completing therapy with a regimen containing fludarabine (or another nucleoside analog) - Hodgkin Disease: Must have received and failed frontline therapy - Follicular lymphoma, marginal zone B-Cell lymphoma, lymphoplasmacytic lymphoma, mantle-cell lymphoma, and indolent T-cell lymphomas: Must have progressed with the most recent remission duration being < 6 months - Follicular lymphoma, marginal zone B-Cell lymphoma, lymphoplasmacytic lymphoma, mantle-cell lymphoma, and indolent T-cell lymphomas: Patients with bulky disease should be considered for debulking chemotherapy before transplant; patients with refractory disease are eligible, unless they have bulky disease and an estimated tumor doubling time of less than one month - Multiple Myeloma: Must have received prior chemotherapy; consolidation of chemotherapy by autografting prior to nonmyeloablative HCT is permitted - Myeloproliferative syndromes - DONOR: Unit selection is based on the cryopreserved total nucleated cell (TNC) dose and matching at HLA-A, B antigen level and DRB1 allele level typing; while HLA-C antigen/allele level typing is not considered in the matching criteria, if available, may be used to optimize unit selection - DONOR: The patient and the cord blood unit(s) must be matched for at least 4 of 6 loci as defined above - DONOR: Selection of two umbilical cord blood (UCB) units is allowed to provide sufficient cell dose Other eligibility criteria may apply. - Patients with fulminant liver failure, cirrhosis with evidence of portal hypertension or bridging fibrosis, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, or correctable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time will be excluded - Patients with ascites related to portal hypertension, bacterial or fungal abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3mg/dL, and symptomatic biliary disease will be excluded - Patients with an available 5-6/6 human leukocyte antigen (HLA)-A, B, DRB1 matched sibling donor - Pregnancy or breastfeeding - Evidence of human immunodeficiency virus (HIV) infection or known HIV positive serology - Uncontrolled viral or bacterial infection at the time of study enrollment - Active or recent (prior 6 month) invasive fungal infection without infectious disease (ID) consult and approval - Active central nervous system malignancy - DONOR: Any cord blood units with < 1.5 x 10^7 total nucleated cells per kilogram recipient weight - DONOR: Any cord blood units without the full maternal testing and negative results for hepatitis A, B, C, HIV, and human T-lymphotropic virus (HTLV-1) viruses Other exclusion criteria may apply. c026b3b20ee9bbfa6c3ea4636dcb090e 7888 Autologous Peripheral Blood Stem Cell Transplant Followed by Donor Bone Marrow Transplant in Treating Patients With High-Risk Hodgkin Lymphoma, Non-Hodgkin Lymphoma, Multiple Myeloma, or Chronic Lymphocytic Leukemia II Mohamed Sorror, MD, MSc 2241.00 11; 18; 36; 38; 43; 48; 57; 64 Bone Marrow and Hematopoietic Stem Cell Transplant (BMT and HSCT); Chronic Lymphoid Leukemia (CLL); Hematologic Malignancies; Hodgkin's Lymphoma; Leukemia; Lymphoma; Multiple Myeloma (MM); Non-Hodgkin's Lymphoma (NHL) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.7888.html http://www.clinicaltrials.gov/ct/search?term=NCT01008462 NCT01008462 This study was designed to combine two types of stem cell transplant. The first would be the use of high-dose chemotherapy and autologous stem cell transplantation (using your own stem cells). This type of stem cell transplant has the advantage of no graft-versus-host disease (GVHD) and very low risk of death, while minimizing the number of cancer cells. Then, the investigators will wait for a period between 40-120 days to allow your body to recover from the high-dose chemotherapy. Then, you will receive the second type of transplant "nonmyeloablative transplant" from your haploidentical family donor. The investigators hope that the donor cells will then eliminate any remaining tumor cells. The investigators are doing this study: - To see if the combined stem cell transplant will help prevent the blood or lymph nodes' cancer from coming back. - To see if the combined stem cell transplant will be safe with no increased toxicities or deaths compared to "nonmyeloablative transplant" alone. Peripheral blood stem cell (PBSC) transplant using stem cells from the patient or a donor may be able to replace immune cells that were destroyed by chemotherapy used to kill cancer cells. These donated stem cells may help destroy cancer cells (graft-versus-tumor effect) Ages Eligible for Study: up to 75 Years Genders Eligible for Study: Both - Must have the capacity to give informed consent - Detectable tumor prior to mobilization regimen - Patients for whom human leukocyte antigens (HLA)-matched unrelated donor search could not be initiated or completed due to insurance reasons, concerns of rapidly progressive disease, and/or discretion of attending physician are eligible for this protocol - Patients with stored autologous stem cells will be allowed - Stem cells from an identical donor could be used for autologous hematopoietic cell transplant (HCT) - Marrow is the preferred source of stem cells from the HLA-haploidentical donor, however, peripheral blood mononuclear cells (PBMC) could be used as stem cell source, after clearance with the Fred Hutchinson Cancer Research Center (FHCRC) principal investigator (PI), in the case of difficulties or contraindications to bone marrow harvest from the donor - Cross-over to other tandem autologous-allogeneic research protocol (#1409) will be allowed if a suitable HLA-matched related or unrelated donor is identified before receiving the allogeneic transplantation and if the patient meets the eligibility criteria of the subsequent study - Cross-over from other tandem autologous-allogeneic research protocol (#1409) will be allowed if the patient loses the suitable HLA-matched related or unrelated donor but has an available HLA-haploidentical donor before receiving the allogeneic transplantation and if the patient meets the eligibility criteria of the subsequent study - Lymphoma: Patients with -- a) Diagnosis of non-Hodgkin lymphoma (NHL) or Hodgkin's lymphoma (HL), of any histological grade, -- b) Refractory or relapsed disease after standard chemotherapy, -- c) High risk of early relapse following autograft alone - Waldenstrom's Macroglobulinemia: must have failed 2 courses of therapy - CLL: - Patients with either a: -- a) Diagnosis of T-cell CLL or T-cell prolymphocytic leukemia (PLL) who have failed initial chemotherapy, patients with T cell CLL or PLL or -- b) Diagnosis of B-cell CLL, B-cell small lymphocytic lymphoma, or B-cell CLL that progressed to PLL who either: - 1.) Failed to meet National Cancer Institute (NCI) Working Group criteria for complete or partial response after therapy with a regimen containing fludarabine (or another nucleoside analog, e.g. 2-chlorodeoxyadenosine [CDA], pentostatin) or experience disease relapse within 12 months after completing therapy with a regimen containing fludarabine (or another nucleoside analog) - 2.) Failed any aggressive chemotherapy regimen, such as fludarabine, cyclophosphamide and rituximab (FCR), at any time point - 3.) Have "17p deletion" cytogenetic abnormality and relapsed at any time point after initial chemotherapy - Harvesting criteria for autologous HCT: -- a) Previously collected PBMC may be used -- b) Circulating CLL cells < 5000 - Marrow involvement with CLL cells < 50% - Multiple myeloma (MM): Patients who - Have received induction therapy for a minimum of 4 cycles - In addition, patients must meet at least one of the following criteria I-IX (I-VII at time of diagnosis or pre-autograft): -- a) Any abnormal karyotype by metaphase analysis except for isolated t(11,14), -- b) Fluorescent in situ hybridization (FISH) translocation 4:14, -- c) FISH translocation 14:16, -- d) FISH deletion 17p, -- e) Beta2-microglobulin > 5.5 mg/ml, -- f) Cytogenetic hypodiploidy -- g) Plasmablastic morphology (>= 2%), -- h) Recurrent or non-responsive (less than partial remission [PR]) MM after at least two different lines of conventional chemotherapy, -- i) Progressive MM after a previous autograft (provided stored autologous CD34 cells are available) - Plasma cell leukemia: after induction chemotherapy - DONOR: Related donors who are genotypically identical for one HLA haplotype and who may be mismatched at the HLA-A, -B, -C or DRB1 loci of the unshared haplotype with the exception of single HLA-A, -B or -C allele mismatches - DONOR: Marrow is the preferred source of stem cells from the HLA-haploidentical donor, however PBMC could be used as stem cell source, after clearance with the FHCRC principal investigator, in the case of difficulties or contraindications to bone marrow harvest from the donor - DONOR: In the case that PBMC will be used as stem cell source, ability of donors < 18 years of age to undergo apheresis without use of a vascular access device; vein check must be performed and verified by an apheresis nurse prior to arrival at the Seattle Cancer Care Alliance (SCCA) - DONOR: Age >= 12 years of age Other eligibility criteria may apply. - Life expectancy severely limited by disease other than malignancy - Seropositive for the human immunodeficiency virus (HIV) - Female patients who are pregnant or breastfeeding - Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment - Patients with available HLA matched related donors - Central nervous system (CNS) involvement with disease refractory to intrathecal chemotherapy - Patients with active non-hematological malignancies (except non-melanoma skin cancers) or those with non-hematological malignancies (except non-melanoma skin cancers) who have been rendered with no evidence of disease, but have a greater than 20% chance of having disease recurrence within 5 years - This exclusion does not apply to patients with non-hematologic malignancies that do not require therapy - Patients with fungal infection and radiological progression after receipt of amphotericin B or active triazole for greater than 1 month - Symptomatic coronary artery disease or ejection fraction < 40% or other cardiac failure requiring therapy (or, if unable to obtain ejection fraction, shortening fraction of < 26%); ejection fraction is required if the patient has a history of anthracyclines or history of cardiac disease; patients with a shortening fraction < 26% may be enrolled if approved by a cardiologist - requiring therapy (or, if unable to obtain ejection fraction, shortening fraction of < 26%); ejection fraction is required if the patient has a history of anthracyclines or history of cardiac disease; patients with a shortening fraction < 26% may be enrolled if approved by a cardiologist - Corrected diffusion capacity of carbon monoxide (DLCO) < 50% of predicted, forced expiratory volume in one second (FEV1) < 50% of predicted, and/or receiving supplementary continuous oxygen; the FHCRC PI of the study must approve of enrollment of all patients with pulmonary nodules - Patient with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, bridging fibrosis, and the degree of portal hypertension; the patient will be excluded if he/she is found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy; the patient will be excluded if he/she is found to have uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3mg/dL, and symptomatic biliary disease - Karnofsky score < 50% for adult patients - Lansky Play-Performance score < 40 for pediatric patients - Patient with poorly controlled hypertension despite multiple antihypertensives - DONOR: Donor-recipient pairs in which the HLA-mismatch is only in the host-versus-graft (HVG) direction - DONOR: Infection with HIV - DONOR: Weight < 20 kg - DONOR: A positive anti-donor cytotoxic crossmatch Other exclusion criteria may apply. 84a1fb6658040fb356aa7209ae0f9bb0 7303 Carmustine, Etoposide, Cytarabine, Melphalan, and Antithymocyte Globulin Followed by Peripheral Blood Stem Cell Transplant in Treating Patients With Autoimmune Neurologic Disease That Did Not Respond to Previous Therapy I/II George Georges, MD 2260.00 7; 11; 16; 60; 127 Autoimmune Diseases; Bone Marrow and Hematopoietic Stem Cell Transplant (BMT and HSCT); Central Nervous System (CNS); Myasthenia Gravis; Non-malignant Condition Bernadette McLaughlin bmclaugh@fhcrc.org 206/667-4916 http://www.fhcrc.org/en/treatment/clinical-trials/detail.7303.html http://www.clinicaltrials.gov/ct/search?term=NCT00716066 NCT00716066 The purpose of this study is to test the safety and effect of an experimental treatment for severe cases of neurological autoimmune diseases. We want to learn what effects, good or bad, this treatment has on study participants’ diseases. We are studying high-dose chemotherapy (drugs called carmustine, etoposide, cytosine arabinoside and melphalan) and antithymocyte globulin, followed by autologous or syngeneic stem cell transplant. (Autologous transplant is a procedure in which a patient receives his or her own stem cells; syngeneic transplant is a procedure in which a patient receives stem cells donated by his or her healthy identical twin.) Treatment on this study will last about 2-3 months. Study participants will be admitted to the University of Washington Medical Center and stay in the hospital for about 3 weeks following the transplant. After that, participants will have follow-up visits at the Seattle Cancer Care Alliance outpatient clinic for about 1-2 months. Study participants will be expected to remain in Seattle for approximately 3 months after treatment for study follow-up. Although preferable, not all study testing will need to be completed at the transplant center. Participants will return to the transplant center or be seen by their doctors for follow-up exams every 3 months for the first year after transplant, then annually for 5 years. Diseases included in this study (patients with other related diseases may also be eligible): • Primary CNS Vasculitis • Rasmussen’s Encephalitis • Autoimmune Peripheral Neuropathy • Autoimmune Cerebellar Degeneration • Gait Ataxia with Late Age Onset Polyneuropathy (GALOP) • Stiff Person Syndrome • Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) • Myasthenia Gravis • Lambert Eaton Myasthenic Syndrome (LEMS) • HTLV-1- Associated Myelopathy (HAM)/ Tropical Spastic Paraparesis (TSP) • Opsoclonus/ Myoclonus (OM ; Anti-Ri) • Neuromyelitis Optica (NMO) • Multiple Sclerosis (MS) 1. Age 70 years or younger 2. Diagnosed with an autoimmune disorder of the central or peripheral nervous system 3. Evidence of disease activity 4. Must have had at least 2 previous lines of standard treatment that failed Other eligibility criteria may apply. 1. Age 71 years or older 2. Pregnant or planning to become pregnant within 1 year of the procedure 3. Tested positive for HIV antibodies (HIV-positive) 4. Lung, heart, liver or kidney impairment (according to study guidelines) 5. Active uncontrolled infection 6. Evidence of myelodysplasia Other exclusion criteria may apply. 8cf9df59f255a86da8da4a92e31b02d2 7432 Treosulfan, Fludarabine Phosphate, and Total-Body Irradiation in Treating Patients With Hematological Cancer Who Are Undergoing Donor Umbilical Cord Blood Transplant II Colleen Delaney, MD, MSc 2275.00 1; 2; 36; 61; 121 Acute Lymphoid Leukemia (ALL); Acute Myeloid Leukemia (AML); Hematologic Malignancies; Myelodysplastic and Myeloproliferative Syndromes (MDS and MPD); Umbilical Cord Blood Transplant (UCBT) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.7432.html http://www.clinicaltrials.gov/ct/search?term=NCT00796068 NCT00796068 This phase II trial studies how well giving treosulfan together with fludarabine phosphate and total-body irradiation (TBI) works in treating patients with hematological cancer who are undergoing donor umbilical cord blood transplant (UCBT). Giving chemotherapy, such as treosulfan and fludarabine phosphate, and TBI before a donor UCBT helps stop the growth of cancer cells and helps stop the patient's immune system from rejecting the donor's stem cells. When the stem cells from a related or unrelated donor, that do not exactly match the patient's blood, are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening Ages Eligible for Study: up to 65 Years Genders Eligible for Study: Both - Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL): Must have < 20% morphologic marrow blasts in an evaluable marrow sample (> 25% of normal cellularity for age) collected less than one month prior to start of conditioning; patients in which adequate marrow/biopsy specimens cannot be obtained to determine remission status by morphologic assessment, but have fulfilled criteria of remission by flow cytometry, recovery of peripheral blood counts with no circulating blasts, and/or normal cytogenetics (if applicable) may still be eligible; reasonable attempts must be made to obtain an adequate specimen for morphologic assessment, including possible repeat procedures; these patients must be discussed with the Principal Investigator prior to enrollment; patients persistently aplastic for greater than one month since completing last chemotherapy are also eligible - Myelodysplastic syndrome (MDS): Any 2001 World Health Organization (WHO) classification subtype; refractory anemia with excess blasts (RAEB)-2 patients may proceed directly to transplant but may also be considered for induction chemotherapy before transplant; patients with >= 20% morphologic marrow blasts require induction therapy to reduce morphologic marrow blasts below 5% before transplant - Chronic myelogenous leukemia: All types, except refractory blast crisis; chronic phase patients must have failed or been intolerant to Gleevec or other tyrosine kinase inhibitors - Patients =< 50 must have performance status score: Karnofsky (for adults) >= 70; Lansky (for children) score >= 50 - Patients > 50 must have Karnofsky performance score >= 70 and comorbidity index < 5 - Adequate cardiac function defined as absence of decompensated congestive heart failure or uncontrolled arrhythmia AND left ventricular ejection fraction >= 35% OR fractional shortening > 22% - Adequate hepatic function; patients with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, histology, and the degree of portal hypertension; patients with fulminant liver failure, cirrhosis with evidence of portal hypertension or bridging fibrosis, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, or correctable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3mg/dL, and symptomatic biliary disease will be excluded - Adequate renal function defined as creatinine =< 2.0 mg/dl (adults) or creatinine clearance > 40 ml/min (pediatrics); all adults with a creatinine > 1.2 or a history of renal dysfunction must have estimated creatinine clearance > 40 ml/min - If recent mold infection, e.g., Aspergillus, must be cleared by infectious disease to proceed - Second hematopoietic cell transplant: must be >= 3 months after prior myeloablative transplant Other eligibility criteria may apply. - Patients =< 65 years with an available 5-6/6 human leukocyte antigen (HLA)-A, B, DRB1 matched sibling donor - Pregnancy or breastfeeding - Evidence of human immunodeficiency virus (HIV) infection or known HIV positive serology - Uncontrolled viral or bacterial infection at the time of study enrollment - Active or recent (prior 6 month) invasive fungal infection without ID consult and approval - Central nervous system (CNS) leukemic involvement not clearing with intrathecal chemotherapy and/or cranial radiation prior to initiation of conditioning (day - 6) - AML in first complete response (CR1) with favorable prognostic cytogenetics (t8;21, t15;17, inv16) and low risk MDS (International Prognostic Scoring System [IPSS] score 0) - Impaired pulmonary function as evidenced by oxygen partial pressure (pO2) < 70 mm Hg and diffusion capacity of carbon monoxide (DLCO) corrected < 70% or pO2 < 80 mm Hg and DLCO corrected < 60%; or receiving supplementary continuous oxygen Other exclusion criteria may apply. 9542fcdc9a7591227d8498409b9959d2 7499 Clofarabine and Low Dose Total Body Irradiation as a Preparative Regimen for Stem Cell Transplant in Leukemia. I Ann Woolfrey, MD 2284.00 11; 36 Bone Marrow and Hematopoietic Stem Cell Transplant (BMT and HSCT); Hematologic Malignancies Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.7499.html http://www.clinicaltrials.gov/ct/search?term=NCT00884572 NCT00884572 Stem cell transplant is an important therapeutic option for pediatric patients with relapsed or refractory leukemia. Although, full myeloablative transplants are widely used for patients with acute leukemia, myeloablative chemo-radiotherapy may not be feasible in some specific settings. These settings include 1) patients with pre-existing health issues and organ toxicities; 2) patients who have relapsed post-ablative transplant and need a second stem cell transplant; and 3) leukemia patients with advanced disease who have been heavily pre-treated. Clofarabine, a new purine nucleoside anti-metabolite, has the advantage of significant antileukemic activity in addition to its possible immuno-suppressive properties. In this study we plan to determine the maximum feasible dose (MFD) of Clofarabine in combination with total body irradiation that can achieve durable donor engraftment without causing excessive toxicity. Ages Eligible for Study: 1 Year to 21 Years Genders Eligible for Study: Both 1. Patients must be greater than or equal to 1 and less than or equal to 21 years of age at the of study entry. 2. Patients must have a diagnosis of ALL or AML. 3. ALL patients must be in clinical remission defined as BM morphology <5% blasts and CNS 1 status. 4. AML patients must be in M1 (<5% blasts) or M2 (<20% blasts) marrow status with CNS 1 status. 5. Patient must have an ANC greater than or equal to 750/ul. 6. Patient must have one of the appropriate donor types as described below: - HLA identical sibling donor - Complete matched unrelated donor, (matched at A, B, C, DR B1 and DQ, B1 at the allelic level based on high resolution typing for Class I and II antigens, 10/10 match) - 1 allelic mis-matched unrelated donor (antigen mis-matches are not allowed) 7. The stem cell source from the donor must be one of the following: - Bone Marrow or Peripheral blood stem cells (PBSC) from a matched related donor - PBSC from an unrelated donor. (Bone marrow is not acceptable for unrelated donors) 8. Karnofsky > 50% for patients > 10 years of age and Lansky > 50% for patients less than or equal to 10 years of age. 9. Female patients of childbearing potential must have a negative serum pregnancy test confirmed within 2 weeks prior to enrollment. 10. Female patients with infants must agree not to breastfeed their infants while on this study. 11. Male and female patients of child-bearing potential must agree to use an effective method of contraception approved by the investigator during the study. 12. Patients must have a calculated creatinine clearance = 70mL/min/m2 as calculated by the Schwartz formula for estimated glomerular filtration rate (GFR) where GFR (ml/min/1.73 m2) = k * Height (cm)/serum creatinine (mg/dl). K is a proportionality constant which varies with age and is a function of urinary creatinine excretion per unit of body size; 0.45 up to 12 months of age; 0.55 children and adolescent girls; and 0.70 adolescent boys. 13. Total serum bilirubin < 2 mg/dL. 14. Aspartate transaminase (AST) and alanine transaminase (ALT) less than or equal to 5 × ULN. 15. Patient must have a shortening fraction (SF) > 25%. If the SF is <25%, patient must have an ejection fraction (EF) by MUGA of >30%. 16. Patient must have pulmonary function as defined below: - DLCO >30% - FVC/TLC >30% - FEV1 > 30% of predicted - Patient is not on continuous oxygen If patient is not old enough or unable to comply with pulmonary function tests, they must have a pulse ox >92% in room air and not be on continuous oxygen. 17. Patient must have signed informed consent Other eligibility criteria may apply. 1. Patients will be excluded if they have evidence of an active, progressive invasive infection. All patients with existing infections at the time study entry should be discussed with the study chair. - Patients may have stable invasive infections and still be eligible. - Patients with infections that are responsive to medical or surgical treatment as shown by radiographic and or microbial assessment may still be eligible. 2. Patients will be excluded if they have an active, uncontrolled systemic fungal, bacterial, viral or other infection. All patients with existing infections at the time of study entry should be discussed with the study chair. - An active uncontrolled infection is defined as exhibiting ongoing signs and symptoms related to the infection (fevers, positive blood cultures, chills, tachycardia, etc) despite appropriate antibiotics or other treatment. 3. Patient has a diagnosis of CML or MDS. 4. Patient has CNS 2 or CNS 3 status. 5. Patient is HIV positive. 6. Current or planned treatment with chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol. 7. Use of investigational agents within 30 days or any anticancer therapy within 2 weeks before study entry. 8. Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney (including dialysis patients), liver, or other organ system that may place the patient at undue risk to undergo treatment. 9. Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment). 10. Any significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance, study participation, follow up, or interpretation of study results. Other exclusion criteria may apply. 4442556617e96feedfdfdcb0519e6d21 7715 Immune Mediated Disorders After Allogeneic Hematopoietic Cell Transplantation NA Stephanie Lee, MD, MPH 2342.00 85; 96; 135 Systemic Sclerosis; Chronic Graft Versus Host Disease (cGVHD); Bronchioloalveolar Carcinoma (BAC) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.7715.html http://www.clinicaltrials.gov/ct/search?term=NCT01206309 NCT01206309 Purpose: The purpose of this research study is to better understand the onset and course of graft versus host disease (GVHD) after stem cell transplant. Genders Eligible for Study: Both - Planned or completed first allogeneic stem cell transplant (any conditioning regimen, graft source, donor type and GVHD prophylaxis regimen) - Signed, informed consent and, if applicable, child assent Other eligibility criteria may apply. - Inability to comply with study procedures - Anticipated survival less than 6 months due to co-morbid disease - Autoimmune disorder or inherited immunodeficiency before HCT - Hematologic relapse or chemotherapy refractory disease at restaging within 1 month of HCT or at the time of enrollment (e.g., > 5% blasts for leukemia; poorly responsive lymphoma) Other exclusion criteria may apply. 563e580248c133da625b60a08ef9e793 8468 Fluticasone Propionate, Azithromycin, and Montelukast Sodium in Treating Patients With Bronchiolitis Obliterans Who Previously Underwent Stem Cell Transplant II Paul Martin, MD 2367.00 36; 96 Hematologic Malignancies; Chronic Graft Versus Host Disease (cGVHD) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8468.html http://www.clinicaltrials.gov/ct/search?term=NCT01307462 NCT01307462 This phase II trial studies how well giving fluticasone propionate, azithromycin, and montelukast sodium (FAM) together works in treating patients with bronchiolitis obliterans who previously underwent stem cell transplant. FAM may be an effective treatment for bronchiolitis obliterans Ages Eligible for Study: 6 Years and older Genders Eligible for Study: Both - New diagnosis of bronchiolitis obliterans syndrome (BOS) after HCT within 3 months of study enrollment: for this study, BOS is defined as: - Forced expiratory volume in 1 second (FEV1) < 75% of the predicted normal and FEV1 to slow or inspiratory vital capacity ratio (FEV1/SVC or FEV1/IVC) =< 0.7, both measured before and after administration of bronchodilator OR - Pathologic diagnosis of BOS demonstrated by lung biopsy - The baseline absolute FEV1 must be >= 10% lower than the pre-transplant absolute FEV1 as defined by the pre-transplant FEV1 minus the baseline FEV1, both measured before administration of a bronchodilator - Participant (or parent/guardian) has the ability to understand and willingness to sign a written consent document Other eligibility criteria may apply. - Recurrent or progressive malignancy requiring anticancer treatment - Known history of allergy to or intolerance of montelukast, zafirlukast, azithromycin, erythromycin, or clarithromycin - Pregnancy or nursing; all females of childbearing potential must have a negative serum or urine pregnancy test < 7 days before study drug administration - Transaminases > 5 X upper limit of normal (ULN) - Total bilirubin > 3 X ULN - Chronic treatment with any inhaled steroid for > 1 month in the past three months - Treatment with montelukast or zafirlukast for > 1 month during the past three months - Treatment with prednisone at > 1.2 mg/kg/day (or equivalent steroid) - Treatment with rifampin or phenobarbital, aspirin at doses > 325 mg/day, or ibuprofen at doses > 1200 mg/day - Treatment with any Food and Drug Administration (FDA) non approved study medication within the past 4 weeks; off-label treatment with an FDA-approved medication is allowed - Chronic oxygen therapy - Evidence of any viral, bacterial or fungal infection involving the lung and not responding to appropriate treatment - Clinical asthma (variable and recurring symptoms of airflow obstruction and bronchial hyper-responsiveness) - Any condition that, in the opinion of the enrolling investigator, would interfere with the subject's ability to comply with the study requirements - Uncontrolled substance abuse or psychiatric disorder - Inability to perform pulmonary function tests (PFT) reliably, as determined by the enrolling investigator or PFT lab - Life expectancy < 6 months at the time of enrollment as judged by the enrolling investigator - Baseline post-bronchodilator FEV1 < 20% of predicted normal before or after albuterol Other exclusion criteria may apply. 0c786c42cee900adfd829dc97cd0dec8 8019 Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies II Paul O'Donnell, MD, PhD 2372.00 36 Hematologic Malignancies Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8019.html http://www.clinicaltrials.gov/ct/search?term=NCT01028716 NCT01028716 This phase II trial is studying how well donor peripheral blood stem cell (PBSC) transplant works in treating patients with hematologic malignancies. Cyclophosphamide when added to tacrolimus and mycophenolate mofetil is safe and effective in preventing severe graft-versus-host disease (GVHD) in most patients with hematologic malignancies undergoing transplantation of bone marrow from half-matched (haploidentical) donors. This approach has extended the transplant option to patients who do not have matched related or unrelated donors, especially for patients from ethnic minority groups. The graft contains cells of the donor's immune system which potentially can recognize and destroy the patient's cancer cells (graft-versus-tumor effect). Rejection of the donor's cells by the patient's own immune system is prevented by giving low doses of chemotherapy (fludarabine phosphate and cyclophosphamide) and total-body irradiation before transplant. Patients can experience low blood cell counts after transplant. Using stem cells and immune cells collected from the donor's circulating blood may result in quicker recovery of blood counts and may be more effective in therapy of the patient's disease than using bone marrow Genders Eligible for Study: Both - Molecular based human leukocyte antigens (HLA) typing will be performed for the HLA-A, -B, -Cw, -DRB1 and -DQB1 loci to the resolution adequate to establish haplo-identity; a minimum match of 5/10 is required - An unrelated donor search is not required for a patient to be eligible for this protocol if the clinical situation dictates an urgent transplant; clinical urgency is defined as 6-8 weeks from referral or low-likelihood of finding a matched, unrelated donor - Acute leukemias (includes T lymphoblastic lymphoma) in remission - Remission is defined as < 5% blasts with no morphological characteristics of acute leukemia (e.g., Auer Rods) in a bone marrow with > 20% cellularity, peripheral blood counts showing ANC > 1000/ul, including patients in complete remission with incomplete platelet recovery (CRp) - Acute Lymphoblastic Leukemia in high risk first complete remission (CR1) as defined by at least one of the following: --- Adverse cytogenetics such as t(9;22), t(1;19), t(4;11), mixed lineage leukemia (MLL) rearrangements --- White blood cell counts > 30,000/mcL --- Patients over 30 years of age --- Time to complete remission > 4 weeks --- Presence of extramedullary disease - Acute Myelogenous Leukemia in high risk CR1 as defined by at least one of the following: --- Greater than 1 cycle of induction therapy required to achieve remission --- Preceding myelodysplastic syndrome (MDS) --- Presence of fms-like tyrosine kinase receptor-3 (Flt3) abnormalities; or French-American-British (FAB) M6 or M7 leukemia OR - adverse cytogenetics for overall survival such as: --- Those associated with MDS --- Complex karyotype (>= 3 abnormalities); or --- Any of the following: inv(3) or t(3;3), t(6;9), t(6;11), + 8 [alone or with other abnormalities except for t(8;21), t(9;11), inv(16) or t(16;16)], t(11;19)(q23;p13.1) - Acute Leukemias in 2nd or subsequent remission - Biphenotypic/Undifferentiated Leukemias in 1st or subsequent CR - High-risk MDS status-post cytotoxic chemotherapy - Burkitt's lymphoma: second or subsequent CR - Chemotherapy-sensitive (complete or partial response) large cell, Mantle Cell or Hodgkin's lymphomas that have failed at least 1 prior regimen of multi-agent chemotherapy and are ineligible for an autologous transplant - Marginal zone B-cell lymphoma or follicular lymphoma that has progressed after at least two prior therapies (excluding single agent Rituxan) - Multiple myeloma (MM) Stage II or III patients who have progressed after an initial response to chemotherapy or autologous hematopoietic stem cell transplantation (HSCT) or MM patients with refractory disease who may benefit from tandem autologous-nonmyeloablative allogeneic transplant - Left ventricular ejection fraction at rest must be >= 35% - Bilirubin =< 2.5 mg/dL - Alanine aminotransferase (ALT) < 5 x upper limit of normal (ULN) - Aspartate aminotransferase (AST) < 5 x ULN - Alkaline phosphatase < 5 x ULN - Serum creatinine within normal range for age, or if serum creatinine outside normal range for age, then renal function (creatinine clearance or glomerular filtration rate [GFR]) > 40 mL/min/1.73m^2 - Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), diffusion capacity of carbon monoxide (DLCO) (diffusion capacity) >= 40% predicted (corrected for hemoglobin); if unable to perform pulmonary function tests, then oxygen (O2) saturation > 92% on room air - Karnofsky/Lansky score >= 60% - Patients who have received a prior allogeneic HSCT and who have either rejected their grafts or who have become tolerant of their grafts with no active GVHD requiring immunosuppressive therapy - DONOR: Donors must be HLA-haploidentical first-degree relatives of the patient; eligible donors include biological parents, siblings, or children, or half-siblings - DONOR: Age >= 12 years - DONOR: Weight >= 40 kg - DONOR: Ability of donors < 18 years of age to undergo apheresis without use of a vascular access device; vein check must be performed and verified by an apheresis nurse prior to arrival at the Seattle Cancer Care Alliance (SCCA) - DONOR: Donors must meet the selection criteria as defined by the Foundation for the Accreditation of Cell Therapy (FACT) and will be screened per the American Association of Blood Banks (AABB) guidelines Other eligibility criteria may apply. - HLA-matched or single allele-mismatched donor able to donate - Pregnancy or breast-feeding - Current uncontrolled bacterial, viral or fungal infection (currently taking medication with evidence of progression of clinical symptoms or radiologic findings) - Patients with primary idiopathic myelofibrosis - DONOR: Positive anti-donor HLA antibody Other exclusion criteria may apply. 41a76d991caba3bd4d39429f43f2806e 8430 Graft-Versus-Host Disease Prophylaxis in Treating Patients With Hematologic Malignancies Undergoing Unrelated Donor Peripheral Blood Stem Cell Transplant III Brenda Sandmaier, MD 2448.00 11; 36; 43; 48 Bone Marrow and Hematopoietic Stem Cell Transplant (BMT and HSCT); Hematologic Malignancies; Leukemia; Lymphoma Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8430.html http://www.clinicaltrials.gov/ct/search?term=NCT01231412 NCT01231412 This randomized phase III trial is studying how well graft-vs-host disease (GVHD) prophylaxis works in treating patients with hematologic malignancies undergoing unrelated donor peripheral blood stem cell transplant. Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant (PBSCT) helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving total-body irradiation (TBI) together with fludarabine phosphate (FLU), cyclosporine (CSP), mycophenolate mofetil (MMF), or sirolimus before transplant may stop this from happening. Genders Eligible for Study: Both - Ages > 50 years with hematologic malignancies treatable by unrelated hematopoietic cell transplant (HCT) - Ages =< 50 years of age with hematologic diseases treatable by allogeneic HCT who through pre-existing medical conditions or prior therapy are considered to be at high risk for regimen related toxicity associated with a high dose transplant (> 40% risk of transplant related mortality [TRM]); this criterion can include patients with a HCT-comorbidity index (CI) score of >= 1; transplants should be approved for these inclusion criteria by both the participating institutions' patient review committees such as the Patient Care Conference (PCC) at the Fred Hutchinson Cancer Research Center (FHCRC) and by the principal investigators at the collaborating centers; patients =< 50 years of age who have received previous high-dose transplantation do not require patient review committee approvals; all children < 12 years must be discussed with the FHCRC principal investigator (PI) prior to registration - Ages =< 50 years of age with chronic lymphocytic leukemia (CLL) (these patients do not require patient review committee approvals) - Ages =< 50 years of age with hematologic diseases treatable by allogeneic HCT who refuse a high-dose HCT; transplants must be approved for these inclusion criteria by both the participating institutions' patient review committee such as PCC at the FHCRC and by the principal investigators at the collaborating centers - The following diseases will be permitted although other diagnoses can be considered if approved by PCC or the participating institutions' patient review committees and the principal investigators: - 1) Aggressive non-Hodgkin lymphomas (NHL) and other histologies such as diffuse large B cell NHL: not eligible for autologous HCT, not eligible for high-dose allogeneic HCT, or after failed autologous HCT - 2) Mantle Cell NHL: may be treated in first complete remission (CR) (Diagnostic lumbar puncture [LP] required pre-transplant) - 3) Low grade NHL: with < 6 month duration of CR between courses of conventional therapy - 4) CLL: must have either: - a) failed to meet National Cancer Institute (NCI) Working Group criteria for complete or partial response after therapy with a regimen containing FLU (or another nucleoside analog, e.g. 2-Chlorodeoxyadenosine [2-CDA], pentostatin) or experience disease relapse within 12 months after completing therapy with a regimen containing FLU (or another nucleoside analog); - b) failed FLU-cyclophosphamide (CY)-Rituximab (FCR) combination chemotherapy at any time point; or - c) have "17p deletion" cytogenetic abnormality; patients should have received induction chemotherapy but could be transplanted in 1st CR; or - d) patients with a diagnosis of CLL (or small lymphocytic lymphoma) or diagnosis of CLL that progresses to prolymphocytic leukemia (PLL), or T-cell CLL or PLL - 5) Hodgkin Lymphoma: must have received and failed frontline therapy - 6) Multiple Myeloma: must have received prior chemotherapy; consolidation of chemotherapy by autografting prior to nonmyeloablative HCT is permitted - 7) Acute Myeloid Leukemia (AML): must have < 5% marrow blasts at the time of transplant - 8) Acute Lymphocytic Leukemia (ALL): must have < 5% marrow blasts at the time of transplant - 9) Chronic Myeloid Leukemia (CML): Patients in CP1 must have failed or be intolerant of tyrosine-kinase inhibitors (TKI); patients beyond CP1 will be accepted if they have < 5% marrow blasts at time of transplant - 10) Myelodysplasia (MDS)/Myeloproliferative Syndrome (MPS): Patients must have < 5% marrow blasts at time of transplant - 11) Waldenstrom's Macroglobulinemia: must have failed 2 courses of therapy - DONOR: FHCRC matching allowed will be grades 1.0 to 2.1: Unrelated donors who are prospectively: - i) Matched for human leukocyte antigen (HLA)-A, B, C, DRB1 and DQB1 by high resolution typing - ii) Only a single allele disparity will be allowed for HLA-A, B, or C as defined by high resolution typing - DONOR: Donors are excluded when preexisting immunoreactivity is identified that would jeopardize donor hematopoietic cell engraftment; this determination is based on the standard practice of the individual institution; the recommended procedure for patients with 10 of 10 HLA allele level (phenotypic) match is to obtain a panel reactive antibody (PRA) screens to class I and class II antigens for all patients before HCT; if the PRA shows > 10% activity, then flow cytometric or B and T cell cytotoxic cross matches should be obtained; the donor should be excluded if any of the cytotoxic cross match assays are positive; for those patients with an HLA Class I allele mismatch, flow cytometric or B and T cell cytotoxic cross matches should be obtained regardless of the PRA results; a positive anti-donor cytotoxic crossmatch is an absolute donor exclusion - DONOR: Patient and donor pairs homozygous at a mismatched allele in the graft rejection vector are considered a two-allele mismatch, i.e., the patient is A*0101 and the donor is A*0102, and this type of mismatch is not allowed - DONOR: Only filgrastim (G-CSF) mobilized PBSC only will be permitted as a hematopoietic stem cell (HSC) source on this protocol Other eligibility criteria may apply. - Patients with rapidly progressive intermediate or high grade NHL - Patients with a diagnosis of chronic myelomonocytic leukemia (CMML) - Patients with refractory anemia with excess blasts (RAEB) who have not received myelosuppressive chemotherapy i.e. induction chemotherapy - Central nervous system (CNS) involvement with disease refractory to intrathecal chemotherapy - Presence of circulating leukemic blasts (in the peripheral blood) detected by standard pathology for patients with AML, MDS, ALL or CML - Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment - Females who are pregnant or breast-feeding - Patients with active non-hematological malignancies (except non-melanoma skin cancers) or those with non-hematological malignancies (except non-melanoma skin cancers) who have been rendered with no evidence of disease, but have a greater than 20% chance of having disease recurrence within 5 years; this exclusion does not apply to patients with non-hematologic malignancies that do not require therapy - Fungal infections with radiological progression after receipt of amphotericin B or active triazole for greater than 1 month - Cardiac ejection fraction < 35% (or, if unable to obtain ejection fraction, shortening fraction of < 26%); ejection fraction is required if age > 50 years or there is a history of anthracycline exposure or history of cardiac disease; patients with a shortening fraction < 26% may be enrolled if approved by a cardiologist - Diffusing capacity of carbon monoxide (DLCO) < 40%, total lung capacity (TLC) < 40%, forced expiratory volume in one second (FEV1) < 40% and/or receiving supplementary continuous oxygen - The FHCRC PI of the study must approve of enrollment of all patients with pulmonary nodules - Patients with clinical or laboratory evidence of liver disease would be evaluated for the cause of liver disease, its clinical severity in terms of liver function, and the degree of portal hypertension; patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bridging fibrosis, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, or symptomatic biliary disease - Karnofsky scores < 60 or Lansky Score < 50 - Patient has poorly controlled hypertension and on multiple antihypertensives - Human immunodeficiency virus (HIV) positive patients - Active bacterial or fungal infections unresponsive to medical therapy - All patients receiving antifungal therapy voriconazole, posaconazole, or fluconazole and who are then randomized to ARM 2 must have sirolimus reduced according to the Standard Practice Antifungal Therapy Guidelines - The addition of cytotoxic agents for "cytoreduction" with the exception of tyrosine kinase inhibitors (such as imatinib), cytokine therapy, hydroxyurea, low dose cytarabine, chlorambucil, or rituxan will not be allowed within three weeks of the initiation of conditioning - DONOR: Donor (or centers) who will exclusively donate marrow - DONOR: Donors who are HIV-positive and/or, medical conditions that would result in increased risk for G-CSF mobilization and harvest of PBSC Other exclusion criteria may apply. 71417c9c915915675cb0fa16a0a051bf 8787 CD19 CAR T Cells for B Cell Malignancies After Allogeneic Transplant I/II Cameron Turtle, PhD, MBBS 2494.00 36; 43; 48; 64 Hematologic Malignancies; Leukemia; Lymphoma; Non-Hodgkin's Lymphoma (NHL) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8787.html http://www.clinicaltrials.gov/ct/search?term=NCT01475058 NCT01475058 This phase I/II trial studies the safety and toxicity of post-transplant treatment with donor T cells engineered to express a chimeric antigen receptor (CAR) targeting CD19 in patients who have had a matched related allogeneic hematopoietic stem cell transplant for a CD19+ B cell malignancy. Ages Eligible for Study: 18 Years to 75 Years Genders Eligible for Study: Both - 1. Patients with - a) CD19+ B cell malignancy who have persistent, relapsed or progressive disease after peripheral blood stem cell transplant from an HLA-matched related donor -OR - b) CD19+ B cell malignancy who are planned for or have had a peripheral blood stem cell transplant from an HLA-matched related donor after myeloablative or non-myeloablative conditioning on a FHCRC transplant protocol and are at high risk of relapse after HCT defined by any one of the disease-specific criteria listed below: -- a. Philadelphia chromosome negative acute lymphoblastic leukemia: --- i. Beyond first complete remission (CR) at the time of pre-transplant evaluation --- ii. First morphologic CR but with evidence of minimal residual disease by flow cytometry, conventional cytogenetics, fluorescence in situ hybridization (FISH) or polymerase chain reaction (PCR) prior to transplant --- iii. First CR with poor risk cytogenetics (t(4:11), t(8;14), hypodiploidy, near triploidy or > 5 cytogenetic abnormalities) at diagnosis -- b. Chronic lymphocytic leukemia, or low grade B cell lymphoma: Lymph nodes greater than or equal to 5 cm at the time of pre-transplant evaluation -- c. Mantle cell lymphoma: Lymph nodes greater than or equal to 2 cm at the time of pre-transplant evaluation -- d. Diffuse large B cell lymphoma, large B cell transformation of an indolent lymphoma or other large B cell lymphoma: Not in CR by conventional computed tomography (CT) criteria or in CR by conventional criteria but with evidence of residual disease by a positive positron emission tomography (PET) scan - 2. Confirmation of tumor diagnosis and expression of CD19 after review by University of Washington Medical Center (UWMC) or Seattle Cancer Care Alliance (SCCA) pathology services - 3. The patient has signed the informed consent form for this study - DONOR: Genotypic or phenotypic HLA-identical family members - DONOR: Express one or more of the following combinations of viral serostatus and HLA allele: - CMV seropositive and HLA-A*0101 positive - CMV seropositive and HLA-A*0201 positive - CMV seropositive and HLA-B*0702 positive - CMV seropositive and HLA-B*0801 positive - EBV seropositive and HLA-A*0201 positive - EBV seropositive and HLA-B*0801 positive - DONOR: Hematocrit >= 35% at enrollment - DONOR: Age >= 18 years - DONOR: The donor has signed the informed consent form for the study Other eligibility criteria may apply. - Philadelphia chromosome positive acute lymphocytic leukemia - Known central nervous system (CNS) tumor (CNS2 or CNS3) that is refractory to intrathecal chemotherapy and/or cranio-spinal radiation; patients with a history of CNS disease that has been effectively treated to CNS1 or lower evidence of disease will be eligible - Human immunodeficiency virus (HIV) seropositive - Significant medical or psychological conditions that would make them unsuitable candidates for T cell therapy - Fertile patients unwilling to use contraception during and for 12 months after protocol enrollment - Pregnant or breast-feeding - DONOR: G-CSF administered within one month prior to the blood draw for T cell collection - DONOR: Unable for any reason to provide a 400 ml blood draw - DONOR: Inadequate peripheral veins for blood collection - DONOR: HIV-1, HIV-2, human T-lymphotropic virus (HTLV)-1 or HTLV-2 seropositive - DONOR: Active hepatitis B or hepatitis C virus infection - DONOR: Positive serologic test for syphilis - DONOR: Aberrant CD45RA isoform expression on all T cells - DONOR: Systolic blood pressure (BP) < 80 or > 200 - DONOR: Heart rate < 50 or > 120, if considered due to cardiac disease - DONOR: Oxygen (O2) saturation < 88% on room air - DONOR- Serum creatinine (Cr) > 3.0 - DONOR: Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 4 x the upper limit of normal - DONOR: Unable to provide informed consent to participate - DONOR: Significant medical conditions (e.g. immunosuppressive therapy) that would make them unsuitable T cell donors - DONOR: Pregnant or nursing Other exclusion criteria may apply. 880cdce597ed1f479764448c0408f671 8826 A Multicenter Access and Distribution Protocol for Unlicensed Cryopreserved Cord Blood Units (CBUs) NA Ann Woolfrey, MD 2531.00 36 Hematologic Malignancies Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8826.html http://www.clinicaltrials.gov/ct/search?term=NCT01351545 NCT01351545 This study is an access and distribution protocol for unlicensed cryopreserved cord blood units (CBUs) in pediatric and adult patients with hematologic malignancies and other indications. Genders Eligible for Study: Both Study Population Recipients of unlicensed cryopreserved cord blood units who are being treated as U.S. transplant centers. Inclusion Criteria: - Patients with FDA-specified indications: Hematological malignancies, Certain lysosomal storage and peroxisomal enzyme deficiency disorders (Hurler syndrome (MPS I), Krabbe Disease (Globoid Leukodystrophy),and X-linked Adrenoleukodystrophy), Primary immunodeficiency diseases, Bone marrow failure, and Beta-thalassemia - Signed informed consent (and signed assent, if applicable) - Pediatric and adult patients of any age Other eligibility criteria may apply. - Patients who are receiving only licensed CBUs - Cord blood transplant recipients at international transplant centers Other exclusion criteria may apply. f2be8eb670d2fb0b080c8b3e4ee5a693 8988 Donor Atorvastatin Treatment for Preventing Severe Acute Graft-Versus-Host Disease in Patients Undergoing Allogeneic Peripheral Blood Stem Cell Transplantation II Marco Mielcarek, MD 2545.00 2; 13; 15; 36; 38; 43; 48; 57; 64; 83 Acute Myeloid Leukemia (AML); Breast Cancer; Burkitt's Lymphoma; Hematologic Malignancies; Hodgkin's Lymphoma; Leukemia; Lymphoma; Multiple Myeloma (MM); Non-Hodgkin's Lymphoma (NHL); Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8988.html http://www.clinicaltrials.gov/ct/search?term=NCT01525407 NCT01525407 This clinical trial studies donor atorvastatin treatment for the prevention of severe acute graft-versus-host disease (GVHD) in patients undergoing myeloablative peripheral blood stem cell (PBSC) transplantation. Giving chemotherapy and total-body irradiation (TBI) before a donor PBSC transplant helps stop the growth of cancer cells. It may also prevent the patient's immune system reject the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving atorvastatin to the donor before transplant may prevent this from happening Genders Eligible for Study: Both Accepts Healthy Volunteers: No - Human leukocyte antigen (HLA)-identical sibling donor - Myeloablative preparative regimen (i.e., >= TBI 12.0 Gy, >= busulfan (BU) 8.0 mg/kg PO, >= BU 6.4 mg/kg intravenously (IV), >= treosulfan 42 g/m^2 IV) according to investigational study or standard treatment plan - Transplantation of PBSC - Cyclosporine (CSP)-based postgrafting immunosuppression - Willingness to give informed consent - DONOR: Age >= 18 years - DONOR: HLA genotypically identical sibling - DONOR: Willingness to give informed consent Other eligibility criteria may apply. - Nonmyeloablative preparative regimen - Participation in an investigational study that has acute GVHD as the primary endpoint - The allogeneic PBSC donor has a contraindication to statin treatment - DONOR: Age < 18 years - DONOR: Active liver disease (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] levels > 2 times the upper limit of normal [ULN]) - DONOR: History of myopathy - DONOR: Hypersensitivity to atorvastatin - DONOR: Pregnancy - DONOR: Nursing mother - DONOR: Current serious systemic illness - DONOR: Concurrent treatment with strong inhibitors of hepatic cytochrome P450 (CYP) 3A4 (i.e. clarithromycin, erythromycin, protease inhibitors, azole antifungals) - DONOR: Current use of statin drug - DONOR: Failure to meet Fred Hutchinson Cancer Research Center (FHCRC) criteria for stem cell donation Other exclusion criteria may apply. d2c3ee3627ec6416fd6077bac7d22121 8989 Donor Atorvastatin -Treatment for Prevention of Severe Acute GVHD After Nonmyeloablative Peripheral Blood Stem Cell Transplantation II Marco Mielcarek, MD 2546.00 2; 15; 36; 38; 43; 48; 57; 64 Acute Myeloid Leukemia (AML); Burkitt's Lymphoma; Hematologic Malignancies; Hodgkin's Lymphoma; Leukemia; Lymphoma; Multiple Myeloma (MM); Non-Hodgkin's Lymphoma (NHL) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8989.html http://www.clinicaltrials.gov/ct/search?term=NCT01527045 NCT01527045 This phase II trial studies how well donor atorvastatin treatment works in preventing severe graft-versus-host disease (GVHD) after nonmyeloablative peripheral blood stem cell (PBSC) transplantation in patients with hematological malignancies. Giving low doses of chemotherapy, such as fludarabine, before a donor PBSC transplantation slows the growth of cancer cells and may also prevent the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also cause an immune response against the body's normal cells (GVHD). Giving atorvastatin to the donor before transplant may prevent severe GVHD. - Ages Eligible for Study: up to 75 Years - Genders Eligible for Study: Both - Availability of human leukocyte antigen (HLA)-identical sibling donor - Transplantation with PBSC - CSP-based postgrafting immunosuppression - Willingness to give informed consent - Patient is enrolled on an investigational nonmyeloablative hematopoietic cell transplant (HCT) protocol or a nonmyeloablative treatment plan with postgrafting CSP that does not use acute GVHD as its primary endpoint (protocol 2546 serves as adjunct protocol) - OR patient is not enrolled on an investigational nonmyeloablative HCT protocol, in which case protocol 2546 serves as an independent primary treatment protocol with the following inclusion and exclusion criteria: - Patients must have a hematologic malignancy treatable by nonmyeloablative HCT; the following diseases will be permitted although other diagnoses can be considered if approved by PCC and the principal investigator: - Aggressive non-Hodgkin lymphomas (NHL) and other histologies such as diffuse large B-cell NHL - not eligible for autologous HCT, not eligible for high-dose allogeneic HCT, or after failed autologous HCT - Mantle-cell NHL - may be treated in first complete remission (CR); (diagnostic lumbar puncture [LP] required pre-transplant) - Low grade NHL - with < 6 month duration of CR between courses of conventional therapy - Chronic lymphocytic leukemia (CLL) - must have either: - a) Failed to meet National Cancer Institute (NCI) Working Group criteria for complete or partial response after therapy with a regimen containing fludarabine phosphate (FLU) (or another nucleoside analog) or experience disease relapse within 12 months after completing therapy with a regimen containing FLU (or another nucleoside analog) - b) Failed FLU-cyclophosphamide (CY)-Rituximab (FCR) combination chemotherapy at any time point; or - c) Have "17p deletion" cytogenetic abnormality; patients should have received induction chemotherapy but could be transplanted in 1st CR - d) Patients with a diagnosis of CLL (or small lymphocytic lymphoma) that progresses to prolymphocytic leukemia (PLL); or - e) Patients with T-cell CLL or PLL - Hodgkin lymphoma - must have received and failed frontline therapy - Multiple myeloma - must have received prior chemotherapy; consolidation of chemotherapy by autografting prior to nonmyeloablative HCT is permitted - Acute myeloid leukemia (AML) - must have < 5% marrow blasts at the time of transplant - Acute lymphocytic leukemia (ALL) - must have < 5% marrow blasts at the time of transplant - Chronic myeloid leukemia (CML) - Patients will be accepted if they are beyond CP1 and if they have received previous myelosuppressive chemotherapy or HCT, and have < 5% marrow blasts at time of transplant - Myelodysplasia (MDS)/ myeloproliferative syndrome (MPS) - Patients must have < 5% marrow blasts at time of transplant - Waldenstrom's macroglobulinemia - must have failed 2 courses of therapy - Patients < 12 years of age must be approved by the principal investigator and by a relevant patient review committee, such as the Fred Hutchinson Cancer Research Center (FHCRC) Patient Care Conference (PCC) - Patients must have either relapsed after previous high-dose chemotherapy and autologous or allogeneic HCT, or else be ineligible for such an approach due to age, failure to mobilize sufficient hematopoietic stem cells, medical comorbidities, or patient refusal - Patients who refuse to be treated on a conventional autologous or allogeneic HCT protocol - DONOR: Age >= 18 years - DONOR: HLA genotypically identical sibling - DONOR: Willingness to give informed consent Other eligibility criteria may apply. - Myeloablative preparative regimen - Participation in an investigational study that has acute GVHD as the primary endpoint - The allogeneic PBSC donor has a contraindication to statin treatment - Patients eligible for and willing to receive potentially curative high-dose chemotherapy and autologous HCT - Cardiac ejection fraction < 30% on multi gated acquisition scan (MUGA) scan or cardiac echo or active symptomatic coronary artery disease; patients with cardiac disease should be evaluated with appropriate cardiac studies and/or cardiology consultation as clinically indicated - Diffusion capacity of carbon monoxide (DLCO) corrected < 40% of predicted, total lung capacity (TLC) < 30% of predicted, forced expiratory volume in one second (FEV1) < 30% of predicted, or receiving continuous supplementary oxygen - Patients with clinical or laboratory evidence of liver disease should be evaluated in conjunction with the gastrointestinal (GI) consult service for the cause of the liver disease, its clinical severity, and the degree of portal hypertension; patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, bridging fibrosis, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, refractory ascites related to portal hypertension, bacterial or fungal liver abscess, chronic viral hepatitis with total serum bilirubin > 3mg/dl, or actively symptomatic biliary disease - Patients with renal failure are eligible; however, patients with pre-existing renal insufficiency will likely have further compromise in renal function and may require dialysis - Patients who are seropositive for human immunodeficiency virus (HIV) - Women who are pregnant or breast-feeding - Fertile men or women unwilling to use contraception during HCT and for 12 months afterward - Patients with active non-hematological malignancies (except for localized non-melanoma skin malignancies); patients with clinically indolent non-hematologic malignancies not requiring active treatment may be eligible, but must be approved by the relevant patient care committee (e.g. FHCRC PCC) and the principal investigator - Karnofsky score < 60 for adult patients - Lansky-Play Performance Score < 50 for pediatric patients - Patients with fungal pneumonia with radiological progression after receipt of amphotericin formulation or mold-active azoles for greater than 1 month - DONOR: Age < 18 years - DONOR: Active liver disease (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] levels > 2 times the upper limit of normal [ULN]) - DONOR: History of myopathy - DONOR: Hypersensitivity to atorvastatin - DONOR: Pregnancy - DONOR: Nursing mother - DONOR: Current serious systemic illness - DONOR: Concurrent treatment with strong inhibitors of hepatic CYP 3A4 (i.e. clarithromycin, erythromycin, protease inhibitors, azole antifungals) - DONOR: Current use of statin drug - DONOR: Failure to meet FHCRC criteria for stem cell donation Other exclusion criteria may apply. 16f306fa762b5f7c141e2eb40edc955a 8996 Double Cord vs. Haploidentical (BMT CTN #1101) III Paul O'Donnell, MD, PhD 2580.00 15; 36; 38; 43; 48; 64 Burkitt's Lymphoma; Hematologic Malignancies; Hodgkin's Lymphoma; Leukemia; Lymphoma; Non-Hodgkin's Lymphoma (NHL) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8996.html http://www.clinicaltrials.gov/ct/search?term=NCT01597778 NCT01597778 Hematopoietic cell transplants (HCT)are one treatment option for people with leukemia or lymphoma. Family members,unrelated donors or banked umbilical cordblood units with similar tissue type can be used for HCT. This study will compare the effectiveness of two new types of bone marrow transplants in people with leukemia or lymphoma: one that uses bone marrow donated from family members with only partially matched bone marrow; and, one that uses two partially matched cord blood units. - Ages Eligible for Study: 18 Years to 70 Years - Genders Eligible for Study: Both - Patients 18 to 70 years old - Patients must be HLA typed at high resolution using DNA based typing at the following HLA-loci: HLA-A, -B, -C and -DRB1 and have available both: a)A related haploidentical BM donor with 2, 3, or 4 HLA-mismatches. The donor and recipient must be HLA identical for at least one allele of the following genetic loci: HLA-A, HLA-B, HLA-C, and HLA-DRB1. b)two UCB units. Each unit must have a minimum of 1.5 x 10^7/kg pre-cryopreserved total nucleated cell dose. For non-red blood cell depleted units, the minimum pre-cryopreserved total nucleated cell dose of each unit must be at least 2.0 x 10^7/kg. Units must be HLA matched at a minimum of 4/6 to the recipient at HLA-A, HLA-B (at low resolution using DNA based typing) and HLA-DRB1 (at high resolution using DNA based typing). Units must be HLA matched at a minimum of 4/6 to each other at HLA-A, HLA-B (at low resolution using DNA based typing) and HLA-DRB1 (at high resolution using DNA based typing), but not necessarily at the same HLA-loci as with the recipient. - Patients must have received either: a) At least one cycle of a cytotoxic chemotherapy regimen or, b) Autologous HCT greater than 6 months and less than 2 years prior to enrollment. - ALL in first complete remission (CR1) that is NOT considered favorable-risk as defined by the presence of at least one of the following: Adverse cytogenetics such as t(9;22), t(1;19), t(4;11), other MLL rearrangements; White blood cell counts of greater than 30,000/mcL at diagnosis; Recipient age older than 30 years at diagnosis; Time to CR greater than 4 weeks - AML in CR1 that is NOT considered as favorable-risk as defined by the presence of at least one of the following: Greater than 1 cycle of induction therapy required to achieve remission; Preceding myelodysplastic syndrome (MDS); Treatment-related AML; Presence of Flt3 abnormalities; FAB M6 or M7 leukemia; or, Adverse cytogenetics for overall survival - Acute Leukemias in 2nd or subsequent CR - Biphenotypic/Undifferentiated Leukemias in first or subsequent CR - Burkitt's lymphoma: second or subsequent CR - Lymphoma fulfilling the following criteria: a) Chemotherapy-sensitive (complete or partial response; large cell, Mantle cell or Hodgkin lymphomas that have failed at least 1 prior regimen of multi-agent chemotherapy and are INELIGIBLE for an autologous transplant; b) Marginal zone B-cell lymphoma or follicular lymphoma that has progressed after at least at least two prior therapies (excluding single agent Rituxan). - Patients with adequate physical function as measured by: 1) Cardiac: Left ventricular ejection fraction at rest must be greater than or equal to 40%, or shortening fraction greater than 25%. 2) Hepatic: Bilirubin less than or equal to 2.5 mg/dL, except for patients with Gilbert's syndrome or hemolysis; ALT, AST, and Alkaline Phosphatase less than 5 x ULN. 3) Renal: Serum creatinine within normal range, or if serum creatinine outside normal range, then renal function (measured or estimated creatinine clearance or GFR) greater than 40 mL/min/1.73m^2. 4) Pulmonary: DLCO (corrected for hemoglobin), FEV1, and FVC greater than 50% predicted. - Karnofsky score greater than or equal to 70%. - Donors must be HLA-haploidentical first-degree relatives of the patient. Eligible donors include biological parents, siblings or half siblings, or children. - For donors less than 18 years old, the maximum recipient weight (kg IBW) should not exceed 1.25 times the donor weight (kg IBW) Other eligibility criteria may apply. - Patients with an 8/8 or 7/8 high resolution HLA-matched (HLA-A, -B, -C, -DRB1) RELATED donor suitable to donate or an 8/8 high resolution HLA-matched UNRELATED donor suitable to donate. HLA matching for both related and unrelated donors to be determined using DNA based typing. - Autologous hematopoietic stem cell transplant less than 6 months prior to enrollment. - Pregnancy or breast-feeding. - Evidence of HIV infection or known HIV positive serology. - Current uncontrolled bacterial, viral or fungal infection (currently taking medication with evidence of progression of clinical symptoms or radiologic findings). - Prior allogeneic HCT. - Patients with history of primary idiopathic myelofibrosis or any severe marrow fibrosis. - Planned use of prophylactic donor lymphocyte infusion (DLI) therapy. - Anti-donor HLA antibodies. Other exclusion criteria may apply. 2bd81f316e74a5934597c883e2a73d49 9144 Bandage Lenses in Treating Patients With Ocular Graft-Versus-Host Disease II Stephanie Lee, MD, MPH 2617.00 96 Chronic Graft Versus Host Disease (cGVHD) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9144.html http://www.clinicaltrials.gov/ct/search?term=NCT01616056 NCT01616056 Researchers are doing this study to see if eye graft-versus-host disease (GVHD) symptoms have improved after two weeks of therapy with bandage lenses. A bandage lens is a disposable soft contact lens used for a diseased or injured part of the eye, called a cornea, to protect or treat it. It is often used after corneal surgery in ophthalmology clinics. Researchers want to know if bandage lenses are helpful in relieving eye symptoms and damage caused by eye GVHD. In this study, researchers want to learn what effects, good or bad, bandage lenses have on people with eye GVHD. They will give the bandage lenses to patients and watch carefully for any side effects Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Diagnosis of chronic GVHD as defined by the National Institutes of Health (NIH) criteria - Ocular symptoms of NIH eye score 2 or greater: - Score 2: Moderate dry eye symptoms partially affecting activities of daily living (ADL) (requiring drops > 3 x per day or punctal plugs), WITHOUT vision impairment - Score 3: Severe dry eye symptoms significantly affecting ADL (special eyewear to relieve pain) OR unable to work because of ocular symptoms OR loss of vision caused by keratoconjunctivitis - No new systemic immunosuppressive medications within 1 month prior to enrollment - Subject has the ability to understand and willingness to sign a written informed consent document Other eligibility criteria may apply. - Absolute neutrophil count < 1000/ul - Known hypersensitivity or allergy to contact lenses - Evidence of any active viral, bacterial, or fungal infection in the eyes that is progressive despite appropriate treatment - Treatment with contact lenses within the previous 3 months for any indication - Active psychiatric disorder, substance abuse or any other reason that would interfere with compliance with the study protocol Other exclusion criteria may apply. c91a25978e78854d8c5ef87c339b51cc 9456 Laboratory Treated T Cells in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Non-Hodgkin Lymphoma, or Acute Lymphoblastic Leukemia I/II David Maloney, MD, PhD 2639.00 15; 36; 43; 48 Burkitt's Lymphoma; Hematologic Malignancies; Leukemia; Lymphoma Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9456.html http://www.clinicaltrials.gov/ct/search?term=NCT01865617 NCT01865617 Purpose This phase I/II trial studies the side effects and best dose of laboratory treated T cells and to see how well they work in treating patients with relapsed or refractory chronic lymphocytic leukemia, non-Hodgkin lymphoma, or acute lymphoblastic leukemia. T cells that are treated in the laboratory before being may make the body build an immune response to kill cancer cells Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both Inclusion Criteria: - Patients with: --- Chronic lymphocytic leukemia (CLL) who are beyond first remission and who have failed combination chemoimmunotherapy with regimens containing a purine analogue and anti-CD20 antibody or who were not eligible for such therapy; patients with fludarabine refractory disease are eligible --- Indolent non-Hodgkin lymphoma (NHL) or mantle cell NHL who are beyond first remission and previously treated with chemoimmunotherapy; patients who have relapsed following autologous hematopoietic cell transplantation (HCT) are eligible --- Aggressive NHL such as diffuse large B-cell lymphoma (DLBCL) who have relapsed or have residual disease following treatment with curative intent; patients must have relapsed disease following high-dose therapy and autologous HCT or not be candidates for high-dose therapy due to inability to collect autologous peripheral blood stem cell (PBSC), advanced age or other co-morbid medical conditions; patients with CD19 expressing, relapsed acute lymphoblastic leukemia (ALL) without higher priority treatment options may be considered for inclusion in this cohort after discussion with the principal investigator (PI) - Confirmation of diagnosis by internal pathology review of initial or subsequent biopsy or other pathologic material at the Fred Hutchinson Cancer Research Center (FHCRC)/Seattle Cancer Care Alliance (SCCA) - Evidence of CD19 expression by immunohistochemistry or flow cytometry on any prior or current tumor specimen - Karnofsky performance status > 70% - Negative pregnancy test for women of childbearing potential - Female patients of childbearing potential must be willing to use a physician approved contraceptive method before, during, and for at least two months after the T cell infusion - Ability to understand and provide informed consent Other eligibility criteria may apply. Exclusion Criteria: - Treatment with other investigational agent(s) within 30 days of enrollment - Patients requiring corticosteroid therapy at a dose of > 15 mg of prednisone per day (or equivalent) - Active autoimmune disease requiring immunosuppressive therapy - Serum creatinine > 2.5 mg/dL - Serum glutamic oxaloacetic transaminase (SGOT) > 5 x upper limit of normal - Bilirubin > 3.0 mg/dL - Forced expiratory volume in one second (FEV1) of < 2.0 L - Diffusing capacity of the lung for carbon monoxide (DLCO) (corrected) < 40% - Significant cardiovascular abnormalities as defined by any one of the following: congestive heart failure, clinically significant hypotension, symptomatic coronary artery disease, or a documented ejection fraction of < 35% - Patients who are human immunodeficiency virus (HIV) seropositive or who have active hepatitis B or C - Men or women of reproductive ability who are unwilling to use effective contraception or abstinence - Uncontrolled active infection (bacterial, viral, fungal, mycobacterial) requiring treatment with intravenous antibiotics, antiviral or antifungal agents, or long-term treatment with oral agents - Anticipated survival of < 3 months Other exclusion criteria may apply. a5e9930ee9f71444b522b77f4e8f17b9 8246 Bendamustine Hydrochloride, Dexamethasone, and Filgrastim For Peripheral Blood Stem Cell Mobilization in Treating Patients With Refractory or Recurrent Lymphoma or Multiple Myeloma II Ajay Gopal, MD 7176 36; 38; 43; 48; 57 Hematologic Malignancies; Hodgkin's Lymphoma; Leukemia; Lymphoma; Multiple Myeloma (MM) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8246.html http://www.clinicaltrials.gov/ct/search?term=NCT01110135 NCT01110135 This phase II trial is studying how well giving bendamustine hydrochloride, etoposide, dexamethasone, and filgrastim together for peripheral stem cell mobilization works in treating patients with refractory or recurrent lymphoma or multiple myeloma. Giving chemotherapy, such as bendamustine hydrochloride, etoposide, and dexamethasone, before a peripheral stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. Giving colony-stimulating factors, such as filgrastim, and certain chemotherapy drugs helps stem cells move from the bone marrow to the blood so they can be collected and stored. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Patients must have relapsed or primary refractory lymphoid malignancy (including B-cell, T-cell, or Hodgkin lymphoma), or multiple myeloma; other transplant eligible diagnoses (e.g. germ cell tumor) can be included with principal investigator (PI) approval - World Health Organization (WHO) classification of patients' malignancies must be provided - Patients with lymphoid malignancies must have a computed tomography (CT) of chest, abdomen, and pelvis within six weeks of enrollment; patients with evidence of lymphadenopathy in the neck must have a CT of neck - Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 - Absolute neutrophil count (ANC) >= 1,500/mm^3 - Platelets >= 100,000/mm^3 (without transfusion or growth factor support) - Creatinine clearance (CrCl) greater than 50/ml per minute (all tests must be performed within 28 days prior to registration) - Total bilirubin < 1.5 times upper limit of normal - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 times upper limit of normal - All patients must be informed of the investigational nature of this study and have given written consent in accordance with institutional and federal guidelines - Adequate venous access plan in place for apheresis procedure - Three or fewer prior myelotoxic treatment regimens (specific regimens include ifosfamide, carboplatin and etoposide [ICE]; cisplatin, cytarabine, and dexamethasone [DHAP]; methotrexate [MTX]/high-dose cytarabine [HiDAC]; cyclophosphamide, vincristine, doxorubicin, and dexamethasone [hyperCVAD]; bortezomib, thalidomide, dexamethasone and 4-day continuous infusions of cisplatin, doxorubicin, cyclophosphamide, and etoposide [VTD-PACE]) Other eligibility criteria may apply. - Patients known positive for human immunodeficiency virus (HIV), or infectious hepatitis type B or C - Pregnant or nursing women; men or women of reproductive potential may not participate unless they have agreed to use an effective contraceptive method - Greater than six prior cycles of lenalidomide therapy - Patients who have previously demonstrated resistance to bendamustine therapy (i.e. no response or progression w/in 6 months) - Fludarabine or other nucleoside analog (except gemcitabine or cytarabine) therapy within 24 months of registration; patients with limited exposure to fludarabine/other nucleoside analog therapy within 24 months may be considered eligible with review and approval by the PI or Co-PI prior to study entry - Symptomatic cardiopulmonary disease - Prior autologous or allogeneic transplantation - Prior radioimmunotherapy within 12 weeks of registration - Prior failed (< 5 x 10^6 CD34/kg) PBSC collection due to inability to mobilize stem cells - Prior pelvic or spinal irradiation - Previous systemic chemotherapy/immunotherapy within 3 weeks before study entry - Concurrent use of other anti-cancer agents or experimental treatments - Known allergy or intolerance to bendamustine, mannitol, GCSF or dexamethasone - More than 3 cycles of myelotoxic salvage chemotherapy within the past 4 months (specific regimens include ICE, DHAP, MTX/HiDAC, hyperCVAD, VTD-PACE) Other exclusion criteria may apply. f978293735b032fbe72e69b3fc85611f 8405 NA Monique Cherrier, PhD 7279 99; 114 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8405.html http://www.clinicaltrials.gov/ct/search?term=7279 7279 KEYWORDS: - Memory - Cognition - Survivor - Dysfunction - Thinking problems - Attention problems Contact Email: wellness@u.washington.edu Contact Phone: 1-888-577-1913 Other eligibility criteria may apply. Other exclusion criteria may apply. 9387a9c48d3a4a9d800b0327670d21cc 8870 PPX and Concurrent Radiation for Newly Diagnosed Glioblastoma Without MGMT Methylation II Maciej Mrugala, MD, PhD 7591 6; 12; 16; 32; 83 Astrocytomas; Brain Cancer; Central Nervous System (CNS); Glioblastoma Multiforme; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8870.html http://www.clinicaltrials.gov/ct/search?term=NCT01402063 NCT01402063 To obtain preliminary data in a randomized phase II study whether PPX/RT improves progression-free survival as compared to temozolomide/RT for patients with GBM without MGMT methylation. - Ages Eligible for Study: 18 Years and older - Genders Eligible for Study: Both - Histologically proven diagnosis of glioblastoma or gliosarcoma (WHO grade IV) - GBM must have unmethylated MGMT as determined by central laboratory - Diagnosis of GBM must be made by biopsy or surgical excision, either partial or complete; as long as there is sufficient tissue to determine MGMT status - No prior chemotherapy or radiation for brain tumor - Must be able to tolerate brain MRIs. - *A diagnostic contrast-enhanced MRI must be performed postoperatively within 42 days prior to study registration. - KPS >60. - Age > 18 - Life expectancy of at least 3 months. - Absolute neutrophil count > 1500/mm3, Platelets > 100,000/mm, - Creatinine < 2 x ULN - ALT or AST < 3 x upper limit of normal (ULN) and total bilirubin < 1.5x ULN. - Patients with a prior history of low grade glioma who did not receive prior radiation or chemotherapy with transformation to grade IV brain tumor are eligible. - Women must be non-lactating, and surgically sterile, post-menopausal or have a negative serum pregnancy test and agree to use adequate birth control. Males must agree to use adequate birth control. - Voluntary, signed informed consent. Other eligibility criteria may apply. - Acute infection or other medical condition that would impair study treatment - No other active invasive malignancy unless disease free for at least 3 years. - Prior temozolomide or PPX. - Prior use of Gliadel wafers or any other intratumoral or intracavitary treatment are not permitted. - Prior radiotherapy to the head or neck (except for T1 glottic cancer), resulting in overlap of radiation fields. - No diffuse leptomeningeal disease, or gliomatosis cerebri. - Use of any other experimental chemotherapy drug within the 60 days prior to randomization and during the trial. (Use of a non-chemotherapy investigational agent must be approved by the Brown University Oncology Group) Other exclusion criteria may apply. 048d2bb65bf2e3f3c08030a2391eb350 9006 Eribulin Mesylate in Treating Patients With Recurrent or Metastatic Salivary Gland Cancer II Renato Martins, MD, MPH 7674 35; 56; 76; 83 Head and Neck Cancer; Mouth Cancer; Salivary Gland Cancer; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9006.html http://www.clinicaltrials.gov/ct/search?term=NCT01613768 NCT01613768 Researchers are doing a research study to examine the use of eribulin (eribulin mesylate) in patients with salivary gland cancer. Researchers want to know if eribulin is safe and effective in treating salivary gland cancer Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Patients must have histologically or cytologically documented salivary gland cancers; patients that do not have a salivary gland primary must have one of the following histologies - adenoid cystic carcinoma, mucoepidermoid carcinoma, acinic cell carcinoma - Patients must have recurrent and/or metastatic disease that is progressive and not amenable to surgery or curative radiotherapy occurring within 6 months of study entry, as evidenced by: at least a 20% increase in radiographically or clinically measurable disease, appearance of any new lesions, or deterioration in clinical status - Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 - Patients with measurable disease per RECIST 1.1 criteria ----- * At least one lesion of >= 1.5 cm in long-axis diameter for non lymph nodes or >= 1.5 cm in short-axis diameter for lymph nodes which is serially measurable according to RECIST 1.1 using either computerized tomography (CT) or magnetic resonance imaging (MRI) ----- * Lesions that have had radiotherapy must show evidence of progressive disease (PD) based on RECIST 1.1 to be deemed a target lesion - Absolute neutrophil count >= 1,500/µL - Platelets >= 100,000/µL - Creatinine clearance >= 40 mL/min - Bilirubin =< 1.5 upper limit of normal (ULN) - Alkaline phosphatase =< 3 ULN; if total ALP is > 3 x ULN (in the absence of liver metastasis) or > 5 x ULN in subjects with liver metastasis AND the subject is known to have bone metastases, then liver ALP iso-enzyme should be used to assess liver function rather than total ALP - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 X ULN - Women of child-bearing potential (WOCP) and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of study participation - Life expectancy of > 12 weeks - Signed and dated informed consent document indicating that the patient has been informed of all the pertinent aspects of the trial prior to enrollment Other eligibility criteria may apply. - Patients with symptomatic central nervous system (CNS) metastases must have stable disease after treatment with surgery or radiation therapy - Second primary malignancy that is clinically detectable or clinically significant at the time of consideration for study enrollment - Radiotherapy within 14 days of study treatment - Major surgery within 21 days of study treatment; minor surgery within 2 weeks of study treatment; placement of vascular access device and biopsies allowed and is not considered major or minor surgery - Treatment with any chemotherapy or investigational agents within 4 weeks of the start of study treatment; subjects must have recovered from toxicities of prior therapy - Patients with peripheral neuropathy >= grade 2 - Significant cardiovascular impairment: congestive heart failure > class II according to the New York Heart Association (NYHA), unstable angina or myocardial infarction within 6 months of enrollment, or serious cardiac arrhythmia (> grade 2) - Concomitant severe or uncontrolled medical disease - Significant psychiatric or neurologic disorder which would compromise participation in the study - Pregnant or breast-feeding females Other exclusion criteria may apply. e266bf15c8b796cfb68ba23e9bb74f80 8279 Bendamustine Hydrochloride, Rituximab, Etoposide, and Carboplatin in Treating Patients With Relapsed or Refractory Lymphoid Malignancies and Select Untreated Lymphomas I Ajay Gopal, MD PSOC 2502 36; 48 Hematologic Malignancies; Lymphoma Jennifer Roden 206/288-6721 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8279.html http://www.clinicaltrials.gov/ct/search?term=NCT01165112 NCT01165112 This phase I/II trial is studying the side effects and best dose of bendamustine hydrochloride when given together with carboplatin, etoposide, and rituximab in treating patients with relapsed or refractory lymphoid malignancies and select untreated lymphomas. Drugs used in chemotherapy, such as bendamustine hydrochloride, etoposide, and carboplatin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving bendamustine hydrochloride together with carboplatin, etoposide, and rituximab may kill more cancer cells Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Patients must have relapsed or primary refractory lymphomas: diffuse large B cell lymphoma (DLBCL) or Hodgkin's lymphoma (HL); patients with other lymphoid malignancies such as T- cell, or lymphomas that are not curable with anthracycline based therapy (e.g. mantle cell lymphoma [MCL], follicular lymphoma [FL], marginal zone lymphoma [MZL], lymphoplasmacytic lymphoma [LPL]) are eligible with protocol Chair review and approval; note: the goal is to have a minimum of 20 patients with DLBCL and 20 patients with HL - World Health Organization (WHO) classification of patient's malignancies must be provided - Patients must have measurable disease defined as lesions that can be accurately measured in two dimensions by computed tomography (CT), magnetic resonance imaging (MRI), medical photograph (skin or oral lesion), plain x-ray, or other conventional technique and a greatest transverse diameter of 1 cm or greater; or palpable lesions with both diameters >= 2 cm; (Note: CT scans remain the standard for evaluation of nodal disease) - Patients must have a CT of chest, abdomen, and pelvis within 28 days of enrollment; patients with evidence of lymphadenopathy in the neck must have a CT of neck - Patients should not have evidence of active central nervous system lymphoma - Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 - Absolute neutrophil count (ANC) >= 1,500/mm^3 (without transfusion or growth factor support); exception: patients with cytopenias due to disease, that do not meet these criteria, will be considered eligible with review and approval by the principal investigator (PI) or Co-PI prior to study entry - Platelets >= 100,000/mm^3 (without transfusion or growth factor support); exception: patients with cytopenias due to disease, that do not meet these criteria, will be considered eligible with review and approval by the PI or Co-PI prior to study entry - Serum creatinine < 1.5 mg/dl or creatinine clearance greater than 50/ ml per minute - Total bilirubin < 1.5 times upper limit of normal - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 times upper limit of normal - Patients must have a serum lactate dehydrogenase (LDH) performed within 14 days prior to registration - All patients must be informed of the investigational nature of this study and have given written consent in accordance with institutional and federal guidelines - Patients must be anticipated to complete at least 2 cycles of chemotherapy Other eligibility criteria may apply. - Patients known positive for human immunodeficiency virus (HIV), or infectious hepatitis type B or C - Pregnant or nursing women; men or women of reproductive potential may not participate unless they have agreed to use an effective contraceptive method - Patients with other prior malignancies except for adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, breast or cervical cancer in situ, or other cancer from which the patient has been disease-free for 5 years or greater, unless approved by the protocol Chair or Co-Chair - Patients who are refractory (i.e. not responded or progressed within 6 months) to a carboplatin, cisplatin, bendamustine, or etoposide-based regimen - Patients who have other medical conditions that would contraindicate treatment with aggressive chemotherapy (including active infection, uncontrolled hypertension, congestive heart failure, unstable angina pectoris, or myocardial infarction within the past 6 months, uncontrolled arrhythmia); if the patient's cardiac history is questionable, a measurement of left ventricular ejection fraction should be obtained within 42 days prior to registration; patients with left ventricular ejection fraction < 50% are not eligible - Autologous or allogeneic transplantation within 12 months or radioimmunotherapy within 6 months of registration; prior failed (< 5x10^6 CD34/kg) peripheral blood stem cell (PBSC) collection - Patients who had pelvic radiation within 12 months or received more than 2 prior therapies with myelotoxic regimens; single agent monoclonal antibody treatment is not considered as one therapy; radiation treatment following chemotherapy is not considered as one separated therapy; consolidative therapy will be considered one regimen e.g. salvage therapy followed by conditioning regimen and transplant - Previous chemotherapy/immunotherapy within 3 weeks before study entry - Concurrent use of other anti-cancer agents or experimental treatments - Known hypersensitivity to bendamustine, mannitol, etoposide, carboplatin, or rituximab Other exclusion criteria may apply. af9c09289c36855151c741b72e4b77d2 7603 III George Laramore, MD, PhD 6864 30; 71; 83 Genitourinary Cancer; Prostate Cancer; Solid Tumors Marge Koe 206/598-4127 http://www.fhcrc.org/en/treatment/clinical-trials/detail.7603.html http://www.clinicaltrials.gov/ct/search?term=NCT00567580 NCT00567580 fd9e8059912996fefed857af0629660c 8420 Radiation Therapy With or Without Temozolomide in Treating Patients With Low-Grade Glioma III George Laramore, MD, PhD 7294 12; 33; 83 Brain Cancer; Glioma; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8420.html http://www.clinicaltrials.gov/ct/search?term=NCT00978458 NCT00978458 5ced17a79a865dde56a558db166bedc4 8853 III George Laramore, MD, PhD 7428 35; 42; 44; 56; 62; 76; 89; 90 Head and Neck Cancer; Laryngeal Cancer; Lip and Oral Cavity Cancer; Mouth Cancer; Nasopharyngeal Cancer; Salivary Gland Cancer; Thyroid Cancer; Tongue Cancer Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8853.html http://www.clinicaltrials.gov/ct/search?term=NCT01311063 NCT01311063 c7176ec865900245eb6eace59fea876b 8925 III George Laramore, MD, PhD 7585 13; 83 Breast Cancer; Solid Tumors http://www.fhcrc.org/en/treatment/clinical-trials/detail.8925.html http://www.clinicaltrials.gov/ct/search?term=NCT01349322 NCT01349322 ba1c4afc9bd31cc98559e16f37196ef6 9328 Recombinant Interleukin-15 in Treating Patients With Advanced Melanoma, Kidney Cancer, Non-Small Cell Lung Cancer, or Head and Neck Cancer I John Thompson, MD 7637a 35; 52; 74; 76; 83; 90 Head and Neck Cancer; Melanoma; Renal Cancer; Salivary Gland Cancer; Solid Tumors; Tongue Cancer Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9328.html http://www.clinicaltrials.gov/ct/search?term=NCT01727076 NCT01727076 ccf4d42442de90069384f7ed474edb21 9226 II George Laramore, MD, PhD 7684 9; 83 Bladder Cancer; Solid Tumors George Laramore, MD, PhD (206) 598-4110 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9226.html http://www.clinicaltrials.gov/ct/search?term=NCT00981656 NCT00981656 c7fc47930fe69255d38a9d507ea2efd6 9465 III George Laramore, MD, PhD 7880 83 Solid Tumors http://www.fhcrc.org/en/treatment/clinical-trials/detail.9465.html http://www.clinicaltrials.gov/ct/search?term=NCT00626990 NCT00626990 34ab9dd5b55d5672800d6273a192c894 7054 III Blythe Thomson, MD COG AALL0434 1; 36; 43 Acute Lymphoid Leukemia (ALL); Hematologic Malignancies; Leukemia Seattle Children’s Outpatient Attending MD (206) 987-2106 http://curesearch.org/; http://cancer.seattlechildrens.org/ http://www.fhcrc.org/en/treatment/clinical-trials/detail.7054.html http://www.clinicaltrials.gov/ct/search?term=NCT00408005 NCT00408005 cbc6721f6bb18f16b7d21364ca4c310c 7072 NA Doug Hawkins, MD COG AALL06N1 1; 36; 43 Acute Lymphoid Leukemia (ALL); Hematologic Malignancies; Leukemia Seattle Children’s Outpatient Attending MD (206) 987-2106 http://curesearch.org/; http://cancer.seattlechildrens.org/ http://www.fhcrc.org/en/treatment/clinical-trials/detail.7072.html http://www.clinicaltrials.gov/ct/search?term=NCT00437060 NCT00437060 9c1de6c068368e82ffc822f860d69feb 5873 III J. Russell Geyer, MD COG ACNS0331 12; 33; 51; 70; 83 Brain Cancer; Glioma; Medulloblastoma; Primitive Neuroectodermal Tumor (PNET); Solid Tumors Seattle Children’s Outpatient Attending MD (206) 987-2106 http://www.curesearch.org; http://cancer.seattlechildrens.org/home/ http://www.fhcrc.org/en/treatment/clinical-trials/detail.5873.html http://www.clinicaltrials.gov/ct/search?term=COG+ACNS0331 COG+ACNS0331 46e2c3ad6e7d99127d6fef1bd7a884ab 6839 I Julie Park, MD COG ADVL0413 1; 2; 6; 10; 12; 15; 16; 20; 28; 29; 30; 32; 33; 35; 36; 38; 40; 41; 43; 45; 48; 51; 55; 63; 64; 70; 72; 74; 75; 77; 83; 89; 95; 96 Acute Lymphoid Leukemia (ALL); Acute Myeloid Leukemia (AML); Astrocytomas; Bone Cancer; Brain Cancer; Burkitt's Lymphoma; Central Nervous System (CNS); Colon Cancer; Gastrointestinal Cancer; Gastrointestinal Stromal Tumor (GIST); Genitourinary Cancer; Glioblastoma Multiforme; Glioma; Head and Neck Cancer; Hematologic Malignancies; Hodgkin's Lymphoma; Juvenile Myeloid Leukemia (JML); Kidney Cancer; Leukemia; Liver Cancer; Lymphoma; Medulloblastoma; Childhood Cancers, Miscellaneous; Neuroblastoma; Non-Hodgkin's Lymphoma (NHL); Primitive Neuroectodermal Tumor (PNET); Rare Cancers; Renal Cancer; Retinoblastoma; Sarcoma; Solid Tumors; Thyroid Cancer; Wilms' Tumor; Chronic Graft Versus Host Disease (cGVHD) Seattle Children’s Outpatient Attending MD (206) 987-2106 http://curesearch.org/; http://cancer.seattlechildrens.org/home/ http://www.fhcrc.org/en/treatment/clinical-trials/detail.6839.html http://www.clinicaltrials.gov/ct/search?term=NCT00343694 NCT00343694 ed5d6a37354082255344a5bb5469492a 6549 I Julie Park, MD COG ADVL0414 6; 10; 12; 15; 16; 20; 28; 29; 30; 32; 33; 35; 36; 38; 41; 45; 48; 51; 55; 63; 64; 70; 72; 74; 75; 77; 83; 89; 95 Astrocytomas; Bone Cancer; Brain Cancer; Burkitt's Lymphoma; Central Nervous System (CNS); Colon Cancer; Gastrointestinal Cancer; Gastrointestinal Stromal Tumor (GIST); Genitourinary Cancer; Glioblastoma Multiforme; Glioma; Head and Neck Cancer; Hematologic Malignancies; Hodgkin's Lymphoma; Kidney Cancer; Liver Cancer; Lymphoma; Medulloblastoma; Childhood Cancers, Miscellaneous; Neuroblastoma; Non-Hodgkin's Lymphoma (NHL); Primitive Neuroectodermal Tumor (PNET); Rare Cancers; Renal Cancer; Retinoblastoma; Sarcoma; Solid Tumors; Thyroid Cancer; Wilms' Tumor Seattle Children’s Outpatient Attending MD (206) 987-2106 http://curesearch.org/; http://cancer.seattlechildrens.org/home/ http://www.fhcrc.org/en/treatment/clinical-trials/detail.6549.html http://www.clinicaltrials.gov/ct/search?term=NCT00138216 NCT00138216 c8f546eac3938e3d0c62c3ef467a4c83 2831 III Julie Park, MD COG ANBL0032 63; 83 Neuroblastoma; Solid Tumors Seattle Children’s Outpatient Attending MD (206) 987-2106 http://www.curesearch.org; http://cancer.seattlechildrens.org/home/ http://www.fhcrc.org/en/treatment/clinical-trials/detail.2831.html http://www.clinicaltrials.gov/ct/search?term=COG+ANBL0032 COG+ANBL0032 5ed0c4d83c6e49927648874d8fa55ff1 6726 III Julie Park, MD COG ANBL00P3 63; 83 Neuroblastoma; Solid Tumors Seattle Children’s Outpatient Attending MD (206) 987-2106 http://curesearch.org/; http://cancer.seattlechildrens.org/home/ http://www.fhcrc.org/en/treatment/clinical-trials/detail.6726.html http://www.clinicaltrials.gov/ct/search?term=NCT00033293 NCT00033293 b91a64fb4bf0b381c284cacb97157366 7308 III Doug Hawkins, MD COG ARAR0332 83 Solid Tumors Seattle Children’s Outpatient Attending MD (206) 987-2106 http://curesearch.org/; http://cancer.seattlechildrens.org/ http://www.fhcrc.org/en/treatment/clinical-trials/detail.7308.html http://www.clinicaltrials.gov/ct/search?term=NCT00304070 NCT00304070 71245e66d17808ed5f95ff6b89b9bc93 6789 II Doug Hawkins, MD COG AREN0321 30; 41; 55; 74; 77; 83; 95; 129; 130 Genitourinary Cancer; Kidney Cancer; Childhood Cancers, Miscellaneous; Renal Cancer; Sarcoma; Solid Tumors; Wilms' Tumor; Malignant Rhabdoid Tumors (MRT); Clear Cell Sarcoma of the Kidney (CCSK) Seattle Children’s Outpatient Attending MD (206) 987-2106 http://curesearch.org/; http://cancer.seattlechildrens.org/ http://www.fhcrc.org/en/treatment/clinical-trials/detail.6789.html http://www.clinicaltrials.gov/ct/search?term=NCT00335556 NCT00335556 ab6a79a3e4dd92e63f97d52605a1f68d 6975 III Doug Hawkins, MD COG AREN0532 30; 41; 83; 95 Genitourinary Cancer; Kidney Cancer; Solid Tumors; Wilms' Tumor Seattle Children’s Outpatient Attending MD (206) 987-2106 http://curesearch.org/; http://cancer.seattlechildrens.org/ http://www.fhcrc.org/en/treatment/clinical-trials/detail.6975.html http://www.clinicaltrials.gov/ct/search?term=NCT00352534 NCT00352534 eef50b47cb42db4929e5c3a24f152b57 7061 III Doug Hawkins, MD COG AREN0533 30; 41; 74; 83; 95 Genitourinary Cancer; Kidney Cancer; Renal Cancer; Solid Tumors; Wilms' Tumor Seattle Children’s Outpatient Attending MD (206) 987-2106 http://curesearch.org/; http://cancer.seattlechildrens.org/ http://www.fhcrc.org/en/treatment/clinical-trials/detail.7061.html http://www.clinicaltrials.gov/ct/search?term=NCT00379340 NCT00379340 eb356b4235a626564d2b02357ab77d43 7296 III Doug Hawkins, MD COG ARET0231 24; 75; 83 Eye Cancer; Retinoblastoma; Solid Tumors Seattle Children’s Outpatient Attending MD (206) 987-2106 http://www.childrensoncologygroup.org/ http://www.fhcrc.org/en/treatment/clinical-trials/detail.7296.html http://www.clinicaltrials.gov/ct/search?term=NCT00072384 NCT00072384 2fbb8790a1043d60ea36cb609e7c2212 7064 III Doug Hawkins, MD COG ARST0332 77; 83; 131; 132 Sarcoma; Solid Tumors; Dermatofibrosarcoma Protuberans (DFSP); Non-rhabdomyosarcoma Soft Tissue Sarcomas (NRSTS) Seattle Children’s Outpatient Attending MD (206) 987-2106 http://curesearch.org/; http://cancer.seattlechildrens.org/ http://www.fhcrc.org/en/treatment/clinical-trials/detail.7064.html http://www.clinicaltrials.gov/ct/search?term=NCT00346164 NCT00346164 abe6923a8497a7e2a0049dc48f7143b8 6213 III Benjamin Greer, MD GOG 0212 34; 65; 83; 125 Gynecological Cancer; Ovarian Cancer; Solid Tumors; Primary Peritoneal Cancer (PPC) Monica Dherin mdherin@fhcrc.org 206/667-4696 http://www.fhcrc.org/en/treatment/clinical-trials/detail.6213.html http://www.clinicaltrials.gov/ct/search?term=GOG+0212 GOG+0212 850b383eb1ad08a145f64936db030a77 7563 II/III Benjamin Greer, MD GOG 0213 25; 34; 65; 83; 125 Fallopian Cancer; Gynecological Cancer; Ovarian Cancer; Solid Tumors; Primary Peritoneal Cancer (PPC) Monica Dherin 206/667-4696 http://www.fhcrc.org/en/treatment/clinical-trials/detail.7563.html http://www.clinicaltrials.gov/ct/search?term=NCT00565851 NCT00565851 20b5c9c319ef626db13f10a0ad9b7df3 9447 II Benjamin Greer, MD GOG 0229-N 22; 83; 92 Endometrial Cancer; Solid Tumors; Uterine Cancer Monica Dherin 206/667-4696 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9447.html http://www.clinicaltrials.gov/ct/search?term=NCT01642082 NCT01642082 526fbfe101ddb10fb4e9201583fe4b78 7961 II/III Benjamin Greer, MD GOG 0249 22; 34; 83; 92 Endometrial Cancer; Gynecological Cancer; Solid Tumors; Uterine Cancer http://www.fhcrc.org/en/treatment/clinical-trials/detail.7961.html http://www.clinicaltrials.gov/ct/search?term=NCT00807768 NCT00807768 c024b83c36f6457f2fb38aeb73aa6007 8301 III Benjamin Greer, MD GOG 0258 22; 83; 92 Endometrial Cancer; Solid Tumors; Uterine Cancer Monica Dherin 206/667-4696 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8301.html http://www.clinicaltrials.gov/ct/search?term=NCT00942357 NCT00942357 78e48e05cfca456d96d81a8923f785a0 8776 III Benjamin Greer, MD GOG 0261 34; 65; 83; 92 Gynecological Cancer; Ovarian Cancer; Solid Tumors; Uterine Cancer Monica Dherin 206/667-4696 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8776.html http://www.clinicaltrials.gov/ct/search?term=GOG+0261 GOG+0261 9fe56c5c69f01ea4fd42e334acc6478f 8742 II Benjamin Greer, MD GOG 0268 34; 65; 83 Gynecological Cancer; Ovarian Cancer; Solid Tumors Monica Dherin mdherin@fhcrc.org 206/667-4696 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8742.html http://www.clinicaltrials.gov/ct/search?term=NCT01196429 NCT01196429 984216b321cbf00401a9be930b9dccce 6808 I Julie Park, MD NANT 2004-04 63; 83 Neuroblastoma; Solid Tumors Seattle Children’s Outpatient Attending MD (206) 987-2106 http://nant.org/; http://cancer.seattlechildrens.org/ http://www.fhcrc.org/en/treatment/clinical-trials/detail.6808.html http://www.clinicaltrials.gov/ct/search?term=NCT00295919 NCT00295919 1b1b3a9c3462eedabed0a862738bf5e0 6939 I Julie Park, MD NANT 9902 11; 63; 83 Bone Marrow and Hematopoietic Stem Cell Transplant (BMT and HSCT); Neuroblastoma; Solid Tumors Seattle Children’s Outpatient Attending MD (206) 987-2106 http://nant.org/; http://cancer.seattlechildrens.org/ http://www.fhcrc.org/en/treatment/clinical-trials/detail.6939.html http://www.clinicaltrials.gov/ct/search?term=NCT00005835 NCT00005835 a08b8f08bf9e554a85b93972bec73e21 6059 III Tanya Wahl, MD NSABP B-39 13; 83 Breast Cancer; Solid Tumors Nancy Knudsen, RN nknudsen@fhcrc.org 206/667-4692 http://www.fhcrc.org/en/treatment/clinical-trials/detail.6059.html http://www.clinicaltrials.gov/ct/search?term=NCT00103181 NCT00103181 f5a4de3bd1eefb49a2900349a01b8ce8 7621 III Tanya Wahl, MD NSABP B-43 13; 83 Breast Cancer; Solid Tumors Nancy Knudsen, RN 206/667-4692 http://www.fhcrc.org/en/treatment/clinical-trials/detail.7621.html http://www.clinicaltrials.gov/ct/search?term=NCT00769379 NCT00769379 cc1c490769f627c4b93d4d6b9fead266 8615 III Tanya Wahl, MD NSABP B-47 13; 83 Breast Cancer; Solid Tumors Nancy Knudsen, RN 206/667-4692 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8615.html http://www.clinicaltrials.gov/ct/search?term=NCT01275677 NCT01275677 16173c12343c6ce659bc77a7a285acc8 8295 III Tanya Wahl, MD NSABP P-5 20; 28; 83 Colon Cancer; Gastrointestinal Cancer; Solid Tumors Joelle Machia, RN, BA, BSN 206/667-6544 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8295.html http://www.clinicaltrials.gov/ct/search?term=NCT01011478 NCT01011478 a4a113dfa3232a47cc02ef4a9f6099a2 7501 Trabectedin for Patients With Locally Advanced or Metastatic Soft Tissue Sarcoma III Robin Jones 20051530 77; 83 Sarcoma; Solid Tumors Cristina Galer 206/288-7537 http://www.fhcrc.org/en/treatment/clinical-trials/detail.7501.html http://www.clinicaltrials.gov/ct/search?term=NCT00707109 NCT00707109 The objective of this study is to facilitate access to trabectedin for eligible previously treated subjects with soft tissue sarcoma (STS), who cannot be expected to benefit from currently available therapeutic options for treatment of STS but who may benefit from treatment with trabectedin. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Male or female subject aged =18 years. - Unresectable advanced or metastatic histologically proven STS. Eligibility will include desmoplastic small round cell tumor, Ewing's sarcoma, and osteosarcoma. - Subjects must have relapsed or had progressive disease following standard of care treatment with chemotherapy prior to enrollment or intolerant to prior standard of care treatment with chemotherapy due to safety issues. - Recovery from toxic effects of prior therapies to Grade 1 or better according to National Cancer Institute-Common Terminology Criteria of Adverse Events (NCI-CTCAE, Version 3). - Hematologic test results: - Hemoglobin =8 g/dL - Absolute neutrophil count (ANC) =1,500/µL - Platelet count =100,000/µL - Clinical chemistry test results: - If serum creatinine =1.5 times the upper limit of normal (ULN), or if serum creatinine is >1.5 times the ULN, then 24 hour creatinine clearance of >50 cc/min, creatine phosphokinase (CPK) =2.5 times the ULN - Hepatic function test results: - Total bilirubin =ULN, if increased then measure indirectly to rule out Gilbert's syndrome. If direct bilirubin is within normal limits, subject may be considered eligible. - Total alkaline phosphatase =1.5 times the ULN, or if liver metastases are present, then alkaline phosphatase may be =2.5 times the ULN. - AST and ALT must be =2.5 times the ULN. - Female subjects must be surgically sterile, abstinent, or, if sexually active, be practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch) before entry and throughout the study, and have a negative urine or serum pregnancy test result at screening. For male subjects and partners, acceptable methods of birth control include sterilization, barrier contraception, and abstinence. - Subjects must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study. Other eligibility criteria may apply. - Less than 3 weeks from the last dose of radiation therapy; last dose or 4 half lives of systemic cytotoxic therapy; therapy with any investigational agent; less than 2 weeks from the last dose of radiation therapy with any investigational agent or systemic therapy, provided all side effects from those therapies have resolved to Grade 1 or less. - Active viral hepatitis or chronic liver disease. - Unstable cardiac condition, including congestive heart failure or angina pectoris, myocardial infarction within 1 year before enrollment, uncontrolled arterial hypertension or arrhythmias. - Active infection. - Female subject who is pregnant or breast-feeding. Other exclusion criteria may apply. 5cabf09789aaf459448644892e34a051 8232 A First in Man Study to Determine the Safety at Various Dose Levels of AGS-16M8F in Advanced Kidney Cancer I John Thompson, MD 20100220 30; 41; 74; 83 Genitourinary Cancer; Kidney Cancer; Renal Cancer; Solid Tumors Phase 1 Program, Study Line phase1@u.washington.edu 206/288-7551 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8232.html http://www.clinicaltrials.gov/ct/search?term=NCT01114230 NCT01114230 Purpose The purpose of this dose escalation study is to examine the safety and pharmacokinetics (PK) of AGS-16M8F administered in subjects with advanced renal cell carcinoma. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Histologic or cytologic diagnosis (recent or remote) of metastatic renal cell carcinoma (including papillary, clear cell, and excluding transitional cell types) that is not amenable to cure by surgery or other means. - Non-measurable or measurable disease according to Response Criteria for Solid Tumors (RECIST Version 1.1) - Eastern Cooperative Group (ECOG) performance status of 0-1 - Negative pregnancy test (women of childbearing potential) - Hematologic function, as follows: 1) Absolute neutrophil count (ANC) = 1.5 x 109/L 2) Platelet count = 100 x 109/L 3) Hemoglobin = 9 g/dL (transfusions are allowed) - Renal function, as follows: Creatinine = 1.5 x upper limit of normal (ULN), or calculated glomerular filtration rate (GFR) > 50 mL/min if creatinine > 1.5x ULN - Hepatic function, as follows: 1) Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) = 2.5 x ULN or = 5x ULN if known liver metastases 2) Total bilirubin = 1.5 x ULN - International Normalized Ratio (INR) < 1.3 (or = 3.0 if on therapeutic anticoagulation) - Women and men of childbearing potential must be advised and agree to practice effective methods of contraception during the course of the study and for four weeks after the last AGS-16M8F infusion administration Other eligibility criteria may apply. - Past or present documented central nervous system (CNS) tumor or CNS metastasis - Use of any investigational drug (including marketed drugs not approved for this indication) within 4 weeks prior to screening - History of thromboembolic events and bleeding disorders = 3 months (e.g., DVT or PE) - Active angina or Class III or IV Congestive Heart Failure (New York Heart Association CHF Functional Classification System) or clinically significant cardiac disease within 12 months of study enrollment, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, congestive heart failure, uncontrolled hypertension, or arrythmias not controlled by outpatient medication - Major surgery (that requires general anesthesia) within 4 weeks of study enrollment - Women who are pregnant (confirmed by positive pregnancy test) or lactating - Known positive test for human immunodeficiency virus (HIV), hepatitis C, or hepatitis B surface antigen - Active infection requiring treatment with systemic (intravenous or oral) anti-infectives (antibiotic, antifungal, or antiviral agent) within 72 hours of screening Other exclusion criteria may apply. 966f019cd9d7a2e42437c7872555d1e5 8189 Study of MLN8237 in Patients With Castration-Resistant Prostate Cancer Receiving a Standard Docetaxel/Prednisone Regimen II Tia Higano, MD 20100481 30; 71; 83 Genitourinary Cancer; Prostate Cancer; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8189.html http://www.clinicaltrials.gov/ct/search?term=NCT01094288 NCT01094288 Purpose This is a randomized, open-label, multicenter, Phase 2, two-arm study that will evaluate the efficacy and safety of MLN8237 given orally in combination with docetaxel and prednisone as a treatment for castration-resistant prostate cancer (CRPC). It will be preceded by a Phase 1 portion to determine tolerable doses and schedules of MLN8237 and docetaxel to be evaluated in the Phase 2 portion. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Male Each patient must meet all of the following inclusion criteria to be enrolled in the study: - Males 18 years or older - Pathologically confirmed adenocarcinoma of the prostate - PSA > 5 ng/mL or radiographically measurable disease - Evidence of metastatic disease on bone scan or other imaging - Progressive disease after at least 1 hormonal treatment - Concurrent use of an agent for testosterone suppression is required if the patient has not been surgically castrated - Eastern Cooperative Oncology Group (ECOG) performance status 0-2 - Recovered to less than or equal to Grade 1 toxicity (CTCAE), to patient's baseline status (except alopecia) or deemed irreversible from the effects of prior cancer therapy and must have evidence of progressive or persistent disease - Adequate bone marrow, liver and renal function - Any use of opiates must be stable for at least 2 weeks prior to study entry - Patients who agree to practice effective barrier contraception or agree to abstain from heterosexual intercourse - Voluntary written consent - Willing to comply with scheduled visits, treatment plan, laboratory tests and other trial procedures - Suitable venous access for blood sampling Other eligibility criteria may apply. Patients meeting any of the following exclusion criteria are not to be enrolled in the study: - Prior treatment with antineoplastic chemotherapy or radioisotopes for metastatic prostate cancer - Prior or current investigational therapies within 4 weeks before the first dose of MLN8237 - Radiotherapy or antiandrogen therapy for prostate cancer within 4 weeks prior to enrollment - Use of products known to affect PSA levels within 4 weeks of enrollment - Radiotherapy to greater than 25% of bone marrow - Localized radiation within 4 weeks of enrollment - Compromised bone marrow including patients with a superscan result on a bone scan - Major surgery within 4 weeks of study enrollment - Uncontrolled high blood pressure - Patients receiving chronic steroid therapy other than the following: low dose steroid for the control of nausea and vomiting, topical steroid, inhaled steroid or use of dexamethasone - Known severe hypersensitivity to docetaxel or other drugs formulated in polysorbate 80 - Comorbid condition or unresolved toxicity that would preclude administration of docetaxel and prednisone - Medical contraindication to any of the docetaxel pre-medications - Prior history of Grade 2 or greater neurotoxicity or any toxicity that has not resolved to Grade 1 or below - Symptomatic brain or other CNS metastasis - Diagnosis or treatment of another malignancy within 2 years preceding first dose of study drug except nonmelanoma skin cancer or in situ malignancy completely resected - Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C - Patients requiring full systemic anticoagulation - Prior allogeneic bone marrow or other organ transplant - Active infection requiring systemic therapy within 14 days preceding first dose, or other serious infection - History of hemorrhagic or thrombotic cerebrovascular event in the past 12 months - Serious medical or psychiatric illness that could interfere with protocol completion - Inability to swallow oral medication - Uncontrolled pain at baseline, impending complication from bone metastasis and/or presence of urinary obstruction Other exclusion criteria may apply. 29db8beff74cab4283543ce0ed809be2 7955 First in Human Study to Determine the Safety, Tolerability and Preliminary Effectiveness of MDX-1338 (BMS 936564) in Subjects With Acute Myelogenous Leukemia (AML) I Pamela Becker, MD, PhD 20100803 2; 36; 43 Acute Myeloid Leukemia (AML); Hematologic Malignancies; Leukemia Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.7955.html http://www.clinicaltrials.gov/ct/search?term=NCT01120457 NCT01120457 Purpose To determine 1) the safety and tolerability of multiple IV doses of MDX-1338 (BMS-936564) as monotherapy, and 2) the maximum tolerated dose (MTD) of MDX-1338 (BMS-936564) as monotherapy (monotherapy MTD) in subjects with relapsed/refractory AML. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Relapsed/refractory AML (M3 excluded) for which no standard therapies are anticipated to result in a durable remission or are unsuitable for standard therapy. If relapsed, no more than 2 relapses are allowed. If refractory, must be primary refractory to at least 1 induction regimen. Secondary AML subjects from MDS or prior chemotherapy are eligible. MDS-only subjects are not eligible - Life expectancy at least 12 weeks - ECOG Performance Status of 0-2 Other eligibility criteria may apply. - Acute promyelocytic leukemia (M3) - Myelodysplastic syndrome (MDS) - Any other malignancy, excluding basal or squamous cell carcinoma of the skin, cervical carcinoma in situ, localized prostate cancer, or superficial bladder cancer stage 0, from which the subject has not been disease-free for at least 3 years - History of severe hypersensitivity reactions to other monoclonal antibodies - Known central nervous system (CNS) involvement Other exclusion criteria may apply. 23b0db371de15e8ed55dfa86c3ec5fad 8579 A Study in Second Line Metastatic Colorectal Cancer III Veena Shankaran 20101327 20; 28; 73; 83 Colon Cancer; Gastrointestinal Cancer; Rectal Cancer; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8579.html http://www.clinicaltrials.gov/ct/search?term=NCT01183780 NCT01183780 The purpose of this study is to compare overall survival in patients with metastatic colorectal cancer treated with either ramucirumab and FOLFIRI or placebo and FOLFIRI. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Histologically or cytologically confirmed metastatic colorectal cancer (patients are eligible to enroll irrespective of KRAS mutation status) - Confirmed metastatic colorectal cancer - The patient has received first-line combination therapy of bevacizumab, oxaliplatin, and a fluoropyrimidine for metastatic disease and a)Experienced radiographic disease progression during first-line therapy, or b)Experienced radiographic disease progression within 6 months after the last dose of first-line therapy, or c)Discontinued part or all of first-line therapy due to toxicity and experienced radiographic disease progression within 6 months after the last dose of first-line therapy; Note that a patient must have received a minimum of 2 doses of bevacizumab as part of a first-line regimen containing chemotherapy; Note that a patient must not have received more than 2 different fluoropyrimidines as part of a first-line regimen; disease progression is not an acceptable reason for discontinuing one fluoropyrimidine and starting a second fluoropyrimidine - Receipt of no more than 2 prior systemic chemotherapy regimens in any setting (only 1 prior regimen for metastatic disease is permitted); For patients with rectal cancer, sequential neoadjuvant and adjuvant therapy will count as a single systemic regimen - Measurable or nonmeasurable disease based on the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v. 1.1) - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 - Adequate hematologic, renal, hepatic and coagulation function - Consent to provide a historical colorectal cancer tissue sample for assessment of biomarkers and the tumor tissue sample is available - Ability to provide signed informed consent Other eligibility criteria may apply. - Receipt of bevacizumab within 28 days prior to randomization - Receipt of any investigational therapy within 28 days prior to randomization - Receipt of any previous systemic therapy, other than a combination of bevacizumab, oxaliplatin, and a fluoropyrimidine, for first-line treatment of metastatic colorectal cancer Known leptomeningeal disease or brain metastases or uncontrolled spinal cord compression - Experience of any arterial thrombotic or arterial thromboembolic events, including, but not limited to myocardial infarction, transient ischemic attack, or cerebrovascular accident, within 12 months prior to randomization - Pregnant (confirmed by serum beta human chorionic gonadotropin [ß HCG] test within 7 days prior to randomization) or lactating - History of inflammatory bowel disease or Crohn's disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) in the 12 months prior to randomization - Acute or subacute bowel obstruction or history of chronic diarrhea which is considered clinically significant in the opinion of the investigator - Grade 3 or higher bleeding event within 3 months prior to randomization - Experience of any of the following during first-line therapy with a bevacizumab-containing regimen: an arterial thrombotic/thromboembolic event, Grade 4 hypertension, Grade 4 proteinuria, a Grade 3-4 bleeding event, or bowel perforation - Known history or clinical evidence of Gilbert's Syndrome, or is known to have any of the following genotypes: UGT1A1*6/*6, UGT1A1*28/*28, or UGT1A1*6/*28 - Known allergy to any of the study treatment components, including any components used in the preparation of ramucirumab, or other contraindication to receive the study treatments Other exclusion criteria may apply. ae2d0102008f0c31634c36a9b2125c24 8553 Study of Ramucirumab or IMC-18F1 With Docetaxel or Docetaxel Alone as Second-Line Therapy in Participants With Bladder,Urethra, Ureter, or Renal Pelvis Carcinoma II Evan Yu, MD 20101692 9; 74; 83; 91 Bladder Cancer; Renal Cancer; Solid Tumors; Urethral Cancer Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8553.html http://www.clinicaltrials.gov/ct/search?term=NCT01282463 NCT01282463 This multicenter trial will enroll participants with metastatic transitional cell carcinoma of the bladder, urethra, ureter, or renal pelvis who have had disease progression on first-line platinum-based chemotherapy regimens. Participants will be enrolled into 1 of 3 treatment arms: docetaxel; docetaxel and ramucirumab; or docetaxel and IMC-18F1. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Histologically or cytologically confirmed transitional cell carcinoma of the bladder, urethra, ureter, or renal pelvis - Locally advanced or metastatic and unresectable transitional cell carcinoma of the bladder, urethra, ureter, or renal pelvis - Had treatment with a platinum-containing regimen - Disease progression within 12 months of after receiving the last dose of a platinum containing regimen in the neoadjuvant or adjuvant setting, and/or had disease progression while on a platinum-containing regimen or within 12 months after the last dose of therapy in the locally advanced or metastatic setting - Life expectancy of = 3 months - Received no more than 2 prior systemic chemotherapy regimens in any setting - Adequate hematologic function - Adequate coagulation function - Adequate hepatic function - Adequate renal function - If female, is surgically sterile, postmenopausal, or compliant with a highly effective contraceptive method during and for 12 weeks after the treatment period - If male, the patient is surgically sterile or compliant with a contraceptive regimen during and for 12 weeks after the treatment period Other eligibility criteria may apply. - Received more than one prior systemic treatment regimen for metastatic disease - Received prior systemic taxane therapy (except for prior paclitaxel therapy) for Transitional Cell Carcinoma of the bladder, urethra, ureter, or renal pelvis in any setting (neoadjuvant, adjuvant, metastatic). Prior intravesical taxane therapy is allowed - Has received more than one prior anti-angiogenic agent for Transitional Cell Carcinoma of the bladder, urethra, ureter, or renal pelvis - Has received radiation therapy within 4 weeks prior to randomization - Has a history of uncontrolled hereditary or acquired bleeding or thrombotic disorders - Has experienced a Grade = 3 bleeding event (eg, via gastric ulcers, gastric varices, or gross hematuria) within 3 months prior to randomization - Has uncontrolled intercurrent illness including, but not limited to symptomatic anemia, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, psychiatric illness/social situations, or any other serious uncontrolled medical disorders - Has experienced any arterial thrombotic or thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack or cerebrovascular accident, within 6 months prior to randomization - Has known brain metastases, uncontrolled spinal cord compression, or leptomeningeal disease - Has an ongoing or active infection requiring parenteral antibiotic, antifungal, or antiviral therapy - Has known human immunodeficiency virus infection or acquired immunodeficiency syndrome - Has received a prior autologous or allogeneic organ or tissue transplantation - Received chemotherapy within 21 days prior to randomization; and/or is currently enrolled in, or discontinued within 21 days prior to randomization from, a clinical trial involving an investigational product or nonapproved use of a drug or device (other than the study drug[s] used in this study), or is concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study; and/or was treated with anti-angiogenic therapy within 28 days prior to randomization - Has undergone major surgery within 28 days prior to randomization, or subcutaneous venous access device placement within 7 days prior to randomization - Has had a serious nonhealing wound, ulcer, or bone fracture within 28 days prior to randomization - Has an elective or planned major surgery to be performed during the course of the trial - Is pregnant or lactating - Has a concurrent active malignancy other than adequately treated non-melanomatous skin cancer, curatively treated cervical carcinoma in-situ, other noninvasive carcinoma or in-situ neoplasm, or prostate cancer with an undetectable prostate specific antigen (PSA) and no current treatment with hormone therapy - Has an acute/subacute bowel obstruction or history of chronic diarrhea requiring ongoing medical intervention - History of gastrointestinal perforation and/or fistula within 6 months prior to randomization - Has active diverticulitis - Known hypersensitivity to docetaxel or other drugs formulated with polysorbate 80 - Known hypersensitivity to agents of similar biologic composition as ramucirumab DP, IMC-18F1, or other agents that specifically target VEGF Other exclusion criteria may apply. 75b19042d251fd432440d2d212163dc8 8488 A Dose Finding Study With Oral LDK378 in Patients With Tumors Characterized by Genetic Abnormalities in Anaplastic Lymphoma Kinase (ALK) I Laura Chow 20110186 36; 48 Hematologic Malignancies; Lymphoma Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8488.html http://www.clinicaltrials.gov/ct/search?term=NCT01283516 NCT01283516 This study will assess the safety and early efficacy of LDK378 in patients with genetic abnormalities in anaplastic lymphoma kinase (ALK) Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Tumor must be confirmed to be ALK positive Other eligibility criteria may apply. - Pregnant - Active pancreatitis - Active or chronic liver disease - Other protocol-defined inclusion/exclusion criteria may apply Other exclusion criteria may apply. d572998f1f3e3f8cf9956a9b702f8c26 8671 A Study of Trabectedin or Dacarbazine for the Treatment of Patients With Advanced L-sarcoma III Robin Jones 20110545 77; 83 Sarcoma; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8671.html http://www.clinicaltrials.gov/ct/search?term=NCT01343277 NCT01343277 Purpose The purpose of this study is to evaluate whether overall survival for the trabectedin group is superior to the dacarbazine group for patients with advanced L-sarcoma (liposarcoma or leiomyosarcoma) who were previously treated with an anthracycline and ifosfamide. Ages Eligible for Study: 15 Years and older Genders Eligible for Study: Both - Locally advanced or spreading liposarcoma or leiomyosarcoma that has been diagnosed through tissue analysis and is unable to be removed by surgery - Treated with an anthracycline and ifosfamide administered either in combination or as sequential regimens - Measurable disease at baseline in accordance with Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 - Pathology specimens (eg, tumor blocks or unstained slides) for potential centralized pathology review and biomarker studies - Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 Other eligibility criteria may apply. - Prior exposure to trabectedin or dacarbazine - Less than 3 weeks from last dose of systemic cytotoxic therapy, radiation therapy, or therapy with any investigational agent - Other malignancy within past 3 years (exceptions: basal or nonmetastatic squamous cell carcinoma of the skin, cervical carcinoma in situ, or Federation Internationale de Gynecologie et d'Obstetrique (FIGO) Stage 1 carcinoma of the cervix) - Known central nervous system metastasis - Active liver disease, such as chronic viral hepatitis or cirrhosis - Heart attack within 6 months before enrollment - Any condition that, in the opinion of the investigator, would compromise the well-being of the patient or the study or prevent the patient from meeting or performing study requirements Other exclusion criteria may apply. b5ec6af72a417996b7dd9960b21e1ab7 8649 A Phase 1 Study Of PF-05082566 As A Single Agent And In Combination With Rituximab I Ajay Gopal, MD 20110654 36; 48; 64 Hematologic Malignancies; Lymphoma; Non-Hodgkin's Lymphoma (NHL) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8649.html http://www.clinicaltrials.gov/ct/search?term=NCT01307267 NCT01307267 Phase 1 dose escalation study of PF-05082566, a 4-1BB agonist monoclonal antibody (mAb). Safety and dose-finding study of PF-05082566 single agent in patients with solid tumors or b-cell lymphomas, and in combination with rituximab in patients with CD20 positive Non-Hodgkin's Lymphoma (NHL). Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Adequate bone marrow, renal, liver and cardiac function - Exclusion Criteria: - Autoimmune disorders, CNS malignancies Other eligibility criteria may apply. Other exclusion criteria may apply. b138ffd96168fb00826fd44bd4879d57 8798 A Study of Brentuximab Vedotin in Patients With CD30-positive Non-Hodgkin Lymphoma II Andrei Shustov, MD 20110853 36; 48; 64 Hematologic Malignancies; Lymphoma; Non-Hodgkin's Lymphoma (NHL) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8798.html http://www.clinicaltrials.gov/ct/search?term=NCT01421667 NCT01421667 This is a single-arm, open-label, multicenter, phase 2 clinical trial to evaluate the efficacy and safety of brentuximab vedotin as a single agent in patients with CD30-positive non-Hodgkin lymphoma (NHL). - Ages Eligible for Study: 6 Years and older - Genders Eligible for Study: Both - Histologically-confirmed CD30-positive NHL - Relapsed or refractory disease following at least 1 prior systemic therapy - Measurable disease of at least 1.5 cm as documented by CT - ECOG performance status less than or equal to 2 Other eligibility criteria may apply. - History of another primary invasive malignancy that has not been in remission for at least 3 years - Current diagnosis of systemic or cutaneous anaplastic large cell lymphoma or mycosis fungoides - B cell lymphoma previously treated with only single-agent rituximab or corticosteroids as monotherapy - Known cerebral/meningeal disease Other exclusion criteria may apply. 317b6332e531567532cfbff05e4f43b8 9010 Gemcitabine and ON 01910.Na in Previously Untreated Metastatic Pancreatic Cancer (ONTRAC) III Andrew Coveler, MD 20111067 66; 83 Pancreatic Cancer; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9010.html http://www.clinicaltrials.gov/ct/search?term=NCT01360853 NCT01360853 The question being asked in this study is: Will patients with advanced pancreatic cancer live significantly longer if they are treated with a combination of Gemcitabine and ON 01910.Na than if they are treated with Gemcitabine alone? There are two parts to this study. In the first part of the study, patients with metastatic pancreatic cancer who have received no prior chemotherapy for this disease will be assigned by chance either to the group that will be treated with both Gemcitabine and ON 01910.Na (about 100 patients will be in this group) or, to the group that will be treated with Gemcitabine only (about 50 patients will be in this group). How long patients survive in the 2 groups will be compared. If it looks like there is no difference between the groups, the study will stop. If it looks like patients in the group that were treated with both Gemcitabine and ON 01910.Na survive longer, the study will continue into a second part where more patients will be treated in order to confirm and better understand the findings of the first part of the study. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Patients at least 18 years old presenting with histopathologically or cytologically confirmed metastatic adenocarcinoma of the pancreas; metastatic disease is defined as disease which has spread beyond the peri-pancreatic lymph nodes. - Patients must have received no prior chemotherapy for pancreatic cancer, including adjuvant chemotherapy. - Measurable disease, defined as lesions that can be accurately measured in at least 1 dimension with longest diameter (LD) = to or>20 mm using conventional techniques or = to or>10 mm with spiral computed tomography (CT) scan; measurable lymph nodes must be = to or >15 mm in the short axis. - ECOG Performance Status of 0, 1, or 2. - Patients must have adequate renal function and serum creatinine = to or < 2.0 mg/dL. - Patients must have adequate liver function as defined by total bilirubin = to or < 2.0 mg/dL and transaminase levels no higher than 3.0 times the institution's upper limit of normal (ULN). Patients with hepatic metastases may have transaminase levels of up to 5.0 times the ULN. - All patients must have a serum albumin = to or >3.0 g/dL. - Patients must have adequate bone marrow (BM) function as defined by a granulocyte count = to or >1,500/mm3, a platelet count = to or >100,000/mm3, and hemoglobin >9 g/dL. - Disease-free period of more than 5 years from prior malignancies other than pancreas (except curatively treated basal cell carcinoma, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix and ductal carcinoma in situ [DCIS] breast disease). - Adequate contraceptive regimen (including prescription oral contraceptives [birth control pills], contraceptive injections, intrauterine device [IUD], double-barrier method [spermicidal jelly or foam with condoms or diaphragm], contraceptive patch, or surgical sterilization) before entry and throughout the study for female patients of reproductive potential or female partners of male patients. - Female patient with reproductive potential must have a negative urine beta human chorionic gonadotropin (bHCG) pregnancy test at Screening. - Willing to adhere to the prohibitions and restrictions specified in this protocol. - Patient must have signed an informed consent document. Other eligibility criteria may apply. - Patients with unresectable locally advanced disease without evidence of disease elsewhere. - Life expectancy of less than 12 weeks. - Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension or seizure disorder. - Active infection not adequately responding to appropriate therapy. - Symptomatic or clinically evident ascites. - Female patients who are pregnant or lactating. - Male patients with female sexual partners who are unwilling to follow the strict contraception requirements described in this protocol. - Major surgery without full recovery or major surgery within 3 weeks of ON 01910.Na treatment start. - Evidence of brain metastases. - Any concurrent administration and/or prior administration within 4 weeks of the first dose of study drug, of radiotherapy, or immunotherapy. - Psychiatric illness/social situations that would limit the patient's ability to tolerate and/or comply with study requirements, or inability to comply with study and/or follow-up procedures (e.g., drug addition, chronic non-compliance, etc.). Other exclusion criteria may apply. cbb80119785ffcf6089b6f39a70fff5d 8690 A Study in Metastatic Cancer and Advanced or Metastatic Unresectable Pancreatic Cancer I/II Andrew Coveler, MD 20111239 28; 66; 83 Gastrointestinal Cancer; Pancreatic Cancer; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8690.html http://www.clinicaltrials.gov/ct/search?term=NCT01373164 NCT01373164 Purpose Phase 1b: To determine the safe and tolerable dose of LY2157299 in combination with gemcitabine in patients with solid malignancy Phase 2a: To compare the overall survival (OS) of patients with Stage II to IV unresectable pancreatic cancer when treated with a combination of LY2157299 and gemcitabine with that of gemcitabine plus placebo. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both Inclusion Criteria: For both Phase 1b and Phase 2 (unless specified in the following), patients are eligible to be included in the study only if they meet all of the following criteria: For Phase 1b: - Have histological or cytological evidence of a diagnosis of cancer that is advanced and/or metastatic disease; that is refractory to standard therapy and/or therapies known to provide clinical benefit or for which no standard therapy exists; and/or in which gemcitabine therapy at the proposed doses and schedule would be considered appropriate treatment for the metastatic disease (eg, pancreatic cancer) - Patients may have received prior chemotherapy, radiotherapy, cancer-related hormone therapy, or other investigational therapy as treatment. There is no limit in the number of previous lines of therapy. For Phase 1b and Phase 2: - Have measurable disease or non-measurable disease, defined according to Response Evaluation Criteria In Solid Tumors (RECIST) - Have given written informed consent prior to any study-specific procedures - Have adequate organ function including: Hematologic: absolute neutrophil count (ANC) greater than or equal to 1.5 x 10^9/L, platelets greater than or equal to 100 x 10^9/L, and hemoglobin greater than or equal to 9 g/dL. Hepatic: bilirubin less than or equal to 1.5 times upper limit of normal (ULN), and alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT)less than or equal to 2.5 times ULN. If the liver has tumor involvement, AST less than or equal to 5 times ULN and ALT less than or equal to 5 times ULN are acceptable. Patients may have endoscopic or radiologic stenting to treat biliary obstructions. If so, then bilirubin must return to less than or equal to 1.5 times ULN and ALP, AST, and ALT to less than or equal to 5 times ULN prior to enrollment. Renal: serum creatinine within normal limits, less than or equal to 1.5 times ULN. - Have a performance status of less than or equal to 2 on the Eastern Cooperative Oncology Group (ECOG) scale - Patients must have recovered from any Grade 3/4 toxicities of previous therapies - Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures - Prior radiation therapy for treatment of cancer is allowed to <25% of the bone marrow, and patients must have recovered from the acute toxic effects of their treatment prior to study enrollment. Prior radiation to the whole pelvis is not allowed. Prior radiotherapy must be completed at least 4 weeks before study entry. - Male and female patients with reproductive potential must use an approved contraceptive method during and for 3 months after discontinuation of study treatment. Women of childbearing potential must have a negative beta-human chorionic gonadotropin (B-HCG) pregnancy test documented within 14 days prior to treatment. If condoms are used as a barrier contraceptive, a spermicidal agent should be added to ensure that pregnancy does not occur. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. For Phase 2: - Have histological or cytological diagnosis of adenocarcinoma of the pancreas that is locally advanced (Stage II, III) or metastatic (Stage IV) and not amenable to resection with curative intent. Patients with previous radical surgery for pancreatic cancer are eligible after progression is documented. If they received adjuvant chemotherapy or chemoradiotherapy with gemcitabine, they can be enrolled if the treatment was completed 3 months before or longer - Tumor tissue or unstained slides are available from original biopsy or resection or other tumor biopsies - Patients may have received previous adjuvant treatment with gemcitabine with or without radiotherapy for pancreatic cancer. Adjuvant treatment must have finished at least 6 months before enrolling. Other eligibility criteria may apply. Patients will be excluded from the study if they meet any of the following criteria: - Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational product or unapproved use of a drug or device (other than the investigational product used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study - Have moderate or severe cardiac disease: - Myocardial infarction within 6 months prior to study entry, unstable angina pectoris, New York Heart Association (NYHA) Class III/IV congestive heart failure, or uncontrolled hypertension - Major abnormalities documented by echocardiography with Doppler (for example, moderate or severe heart valve function defect and/or left ventricular ejection fraction (LVEF) <50%, evaluation based on the institutional lower limit of normal) - Predisposing conditions that are consistent with development of aneurysms of the ascending aorta or aortic stress (for example, family history of aneurysms, Marfan-Syndrome, bicuspid aortic valve, evidence of damage to the large vessels of the heart documented by CT scan or MRI with contrast) - Are unable to swallow tablets or capsules - Are pregnant or breastfeeding - Have any significant medical illnesses that, in the investigator's opinion, cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy - Have a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ), unless in complete remission and off of all therapy for that disease for a minimum of 3 years - Have active infection that would interfere with the study objectives or influence study compliance - Phase 2 only: Endocrine pancreatic tumors or ampullary cancer - Patients with acute or chronic leukemia or with any other disease likely to have a significant bone marrow infiltration (screening not required) - Have previously completed or withdrawn from this study or any other study investigating LY2157299 or any other TGF-ß inhibitor - Have known allergy to LY2157299 or gemcitabine or any ingredient of LY2157299 or gemcitabine formulations Other exclusion criteria may apply. 4d0640132882ad1c7e01c61870a6c38f 9334 A Trial of TH-302 in Combination With Doxorubicin Versus Doxorubicin Alone to Treat Patients With Locally Advanced Unresectable or Metastatic Soft Tissue Sarcoma III Robin Jones 20111252 77; 83 Sarcoma; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9334.html http://www.clinicaltrials.gov/ct/search?term=NCT01440088 NCT01440088 The purpose of this study is to determine whether TH-302 in combination with Doxorubicin is safe and effective in the treatment of Locally Advanced Unresectable or Metastatic Soft Tissue Sarcoma. Ages Eligible for Study: 15 Years and older Genders Eligible for Study: Both - Male or female equal to or greater than 15 years of age - Ability to understand the purposes and risks of the study and has signed or, if appropriate, the subject's parent or legal guardian has signed a written informed consent form approved by the investigator's IRB/Ethics Committee - Pathologically confirmed diagnosis of soft tissue sarcoma of the following histopathologic types: - a) Synovial sarcoma - b) High grade fibrosarcoma - c) Undifferentiated sarcoma; sarcoma not otherwise specified (NOS) - d) Liposarcoma - e) Leiomyosarcoma (excluding GIST) - f) Angiosarcoma (excluding Kaposi's sarcoma) - g) Malignant peripheral nerve sheath tumor - h) Pleomorphic Rhabdomyosarcoma - i) Myxofibrosarcoma - j) Epithelioid sarcoma - k) Undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma (MFH) (including pleomorphic, giant cell, myxoid and inflammatory forms) - Locally advanced unresectable or metastatic disease with no standard curative therapy available and for whom treatment with single agent doxorubicin is considered appropriate. - Recovered from reversible toxicities of prior therapy - Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 - Life expectancy of at least 3 months - Acceptable liver, renal, hematological and cardiac function - All women of childbearing potential must have a negative serum pregnancy test and all subjects must agree to use effective means of contraception Other eligibility criteria may apply. - Prior systemic therapy for advanced or metastatic disease (neoadjuvant therapy followed by surgical resection and adjuvant therapy permitted) - Low grade tumors according to standard grading systems - Prior therapy with ifosfamide or cyclophosphamide or other nitrogen mustards - Prior therapy with an anthracycline or anthracenedione - Prior mediastinal/cardiac radiotherapy - Current use of drugs with known cardiotoxicity or known interactions with doxorubicin - Anti-cancer treatment with radiation therapy, neoadjuvant or adjuvant chemotherapy, targeted therapies, immunotherapy, hormones or other antitumor therapies within 4 weeks prior to study entry (6 weeks for nitrosoureas or mitomycin C) - Significant cardiac dysfunction precluding treatment with doxorubicin - Seizure disorders requiring anticonvulsant therapy unless seizure-free for the last year - Known brain metastases (unless previously treated and well controlled for a period = to or > 3 months) - Previously treated malignancies, except for adequately treated non-melanoma skin cancer, in situ cancer, or other cancer from which the subject has been disease-free for at least 5 years - Severe chronic obstructive or other pulmonary disease with hypoxemia or in the opinion of the investigator any physiological state likely to cause normal tissue hypoxia - Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1, without complete recovery - Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy - Prior therapy with a hypoxic cytotoxin - Subjects who participated in an investigational drug or device study within 28 days prior to study entry - Known infection with HIV, hepatitis B, or hepatitis C - Subjects who have exhibited allergic reactions to a structural compound similar to TH-302,doxorubicin or their excipients - Females who are pregnant or breast-feeding - Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study - Unwillingness or inability to comply with the study protocol for any reason Other exclusion criteria may apply. 866bef028612bc289cec8f650bf4e89d 9011 Efficacy and Safety of GS-6624 With FOLFIRI as Second Line Treatment in Colorectal Adenocarcinoma II Andrew Coveler, MD 20111441 20; 83 Colon Cancer; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9011.html http://www.clinicaltrials.gov/ct/search?term=NCT01479465 NCT01479465 This randomized study compares the efficacy of GS-6624 versus placebo in combination with FOLFIRI in subjects with colorectal cancer. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Metastatic Colorectal Carcinoma with KRAS mutation. - Received first line therapy and discontinued part or all of first line therapy. - Estimated life expectancy > 3 months. - Stage IV disease. - ECOG 0-2. - Adequate hepatic and hematologic function - No major operations within 4 weeks prior to treatment start. Other eligibility criteria may apply. - More than 1 prior chemotherapy regimen for stage 4 colorectal cancer. - Experimental medical treatment within 30 days prior to study entry. - Known or suspected cerebral metastases. - History or presence of any form of cancer, other that colorectal cancer, within the 3 years prior to enrollment. - Known dihydropyrimidine dehydrogenase-deficiency (special screening not required). - Subjects with angina pectoris, poorly controlled ventricular arrhythmias (does not include asymptomatic, occasional premature ventricular contractions), history of clinically significant coronary heart disease or cardiomyopathy, or ECG abnormalities consistent with ischemia. - Uncontrolled hypertension (seated systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg) at Screening. - Clinically active liver disease, including active hepatitis (any etiology) or cirrhosis. - Anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy, retinoid therapy, hormonal therapy) within 21 days prior to randomization - Prior irinotecan therapy for metastatic disease is not permitted. - Systemic fungal, bacterial, viral, or other infection Other exclusion criteria may apply. 00d953862b06cbde1bc214dc51de64b6 8906 Phase III Study of Rindopepimut/GM-CSF in Patients With Newly Diagnosed Glioblastoma (ACT IV) III Maciej Mrugala, MD, PhD 20111531 6; 12; 32; 33; 83 Astrocytomas; Brain Cancer; Glioblastoma Multiforme; Glioma; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8906.html http://www.clinicaltrials.gov/ct/search?term=NCT01480479 NCT01480479 This 2-arm, randomized, phase III study will investigate the efficacy and safety of the addition of rindopepimut (an experimental cancer vaccine that may act to promote anti-cancer effects in patients who have tumors that express the EGFRvIII protein) to the current standard of care (temozolomide) in patients with recently diagnosed glioblastoma, a type of brain cancer. All patients will be administered temozolomide, the standard treatment for glioblastoma. Half the patients will be randomly assigned to receive rindopepimut and half the patients will be randomly assigned to receive a control called keyhole limpet hemocyanin. Patients will be treated in a blinded fashion (neither the patient or the doctor will know which arm of the study the patient is on). Patients will be treated until disease progression or intolerance to therapy and all patients will be followed for survival. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both Among other criteria, patients must meet the following conditions to be eligible for the study: - Adult patients, =/> 18 years old - Newly diagnosed glioblastoma - Attempted surgical resection followed by conventional chemoradiation - Documented EGFRvIII positive tumor status by a Sponsor designated laboratory - No evidence of progressive disease from the post-operative period to the post-chemoradiation period - Candidate for, and agrees to receive, adjuvant (maintenance) temozolomide therapy - Systemic corticosteroid therapy at =/<2 mg of dexamethasone or equivalent per day for at least 3 days prior to randomization - WHO-ECOG Performance Status =/< 2 Other eligibility criteria may apply. Among other criteria, patients who meet the following conditions are NOT eligible for the study: - Stereotactic biopsy only (without further surgical resection) - Presence of diffuse leptomeningeal disease or gliomatosis cerebri - History, presence, or suspicion of metastatic disease - Patients who have received any additional treatment for glioblastoma, aside from surgical resection and chemoradiation with temozolomide - Active systemic infection requiring treatment - History of any malignancy (other than glioblastoma) during the last three years except non-melanoma skin cancer, in situ cervical cancer, treated superficial bladder cancer or cured, early-stage prostate cancer in a patient with PSA level less than the upper limit of normal - Planned major surgery - Evidence of current drug or alcohol abuse - Known allergy or hypersensitivity to keyhole limpet hemocyanin (KLH), GM-CSF (sargramostim; LEUKINE®), polysorbate 80 or yeast derived products, or a history of anaphylactic reactions to shellfish proteins Other exclusion criteria may apply. 3398f8aa235aac3b54640590b7d001d4 8810 Study Evaluating Inotuzumab Ozogamicin In Acute Lymphocytic Leukemia II Andrei Shustov, MD 20111581 1; 18; 36; 43 Acute Lymphoid Leukemia (ALL); Chronic Lymphoid Leukemia (CLL); Hematologic Malignancies; Leukemia Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8810.html http://www.clinicaltrials.gov/ct/search?term=NCT01363297 NCT01363297 The purpose of this study is to assess the safety, tolerability and efficacy at increasing dose levels of inotuzumab ozogamicin in subjects with CD22-positive relapsed or refractory adult acute lymphocytic leukemia (ALL) in order to select the recommended phase 2 dose (RP2D) and schedule. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Subjects with CD22-positive ALL with either refractory disease (i.e. disease progression or no response while receiving their most recent prior anti-cancer therapy), or relapsed disease (i.e. response to their most recent prior anti-cancer therapy with subsequent relapse). - Subjects with Philadelphia chromosome-positive (Ph+) ALL must have failed standard treatment with at least one tyrosine kinase inhibitor. - Adequate renal and hepatic function, and negative pregnancy test for women of childbearing potential. Other eligibility criteria may apply. - Subjects with isolated extramedullary relapse or active central nervous system (CNS) leukemia. - Prior allogeneic hematopoietic stem cell transplant (HSCT) or other anti-CD22 immunotherapy within 4 months, or active graft versus host disease (GvHD) at study entry. - Evidence or history of veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS). Other exclusion criteria may apply. e242c71d4ce003a127e03053f0114950 8718 A Study of RO5429083 in Patients With Metastatic and/or Locally Advanced, CD44-Expressing, Malignant Solid Tumors I Andrew Coveler, MD 20111743 83 Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8718.html http://www.clinicaltrials.gov/ct/search?term=NCT01358903 NCT01358903 This open-label 2-arm study will assess the pharmacokinetics, pharmacodynamics, safety and efficacy of RO5429083 in patients with metastatic and/or locally advanced CD44-expressing malignant solid tumors. In Part A, cohorts of patients will receive RO5429083 intravenously at escalating doses. In Part B, patients will receive 89Zr-labelled RO5429083 in Cycles 1 and/or 2, followed by RO5429083. For all patients there will be an option to continue treatment with RO5429083 until disease progression or unacceptable toxicity occurs. - Ages Eligible for Study: 18 Years and older - Genders Eligible for Study: Both - Adult patients, >/= 18 years of age - Metastatic and/or locally advanced malignant CD44-expressing solid tumors - Patients with disease progression on standard therapy, or have tumors that are not curable by standard therapy - Life expectancy of over 12 weeks Other eligibility criteria may apply. - Concurrent therapy with any other investigational drug - Known or suspected CNS metastases including leptomeningeal metastases - Active bleeding, bleeding diathesis or history of coagulation disorder - Uncontrolled diabetes mellitus - Active or uncontrolled infections - Patients with HIV infections Other exclusion criteria may apply. cc6649f4c89848706f9e426d5040e487 9083 Previous Study | Return to List | Next Study A Study of Rindopepimut/GM-CSF in Patients With Relapsed EGFRvIII-Positive Glioblastoma (ReACT) II Maciej Mrugala, MD, PhD 20111765 32; 83 Glioblastoma Multiforme; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9083.html http://www.clinicaltrials.gov/ct/search?term=NCT01498328 NCT01498328 The purpose of this research study is to find out whether adding an experimental vaccine called rindopepimut (also known as CDX-110) to the commonly used drug bevacizumab can improve progression free survival (slowing the growth of tumors) of patients with relapsed EGFRvIII positive glioblastoma. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both Among other criteria, patients must meet the following conditions to be eligible for the study: - 1.) Age >/= 18 years of age. - 2.) Histologic diagnosis of glioblastoma (WHO Grade IV). - 3.) Previous treatment for glioblastoma must include surgery,conventional radiation therapy and temozolomide (TMZ). - 4.0 First or second relapse of de novo glioblastoma. - 5.) Screening MRI must be obtained at least 4 weeks after any salvage surgery, and at least 12 weeks after radiation therapy. - 6.) KPS of >/= 70%. - 7.) Life expectancy > 12 weeks. - 8.) Documented EGFRvIII positive tumor status by a Sponsor designated laboratory. - 9.) If applicable, systemic corticosteroid therapy must be at a dose of </= 4 mg of dexamethasone or equivalent per day during the week prior to Day 1. - 10.) Evaluable disease Other eligibility criteria may apply. Among other criteria, patients who meet the following conditions are NOT eligible for the study: - 1.) Subjects unable to undergo an MRI with contrast. - 2.) History, presence, or suspicion of metastatic disease - 3.) Prior receipt of vaccination against EGFRvIII. - 4.) Any known contraindications to receipt of study drugs, including known allergy or hypersensitivity to keyhole limpet hemocyanin (KLH), GM-CSF (sargramostim; LEUKINE®), polysorbate 80 or yeast derived products, or a history of anaphylactic reactions to shellfish proteins. - 5.) Use of non-protein based investigational therapy within 14 days prior to Day 1 or use of antibody-based investigational therapy within 28 days prior to Day 1. - 6.) Clinically significant increased intracranial pressure (e.g., impending herniation), uncontrolled seizures, or requirement for immediate palliative treatment - 7.) Evidence of recent hemorrhage on screening MRI of the brain - 8.) Evidence of current drug or alcohol abuse. Other exclusion criteria may apply. bac5f8961ac80a0e299856f69dbcc9e3 8767 BNC105P in Combination With Everolimus/Following Everolimus For Progressive Metastatic Clear Cell Renal Cell Carcinoma I/II Shailender Bhatia, MD 20111792 30; 41; 74; 83 Genitourinary Cancer; Kidney Cancer; Renal Cancer; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8767.html http://www.clinicaltrials.gov/ct/search?term=NCT01034631 NCT01034631 The purpose of this study is to determine whether BNC105P in combination with/following everolimus is effective in the treatment of progressive metastatic clear cell renal cell carcinoma following prior tyrosine kinase inhibitors. - Ages Eligible for Study: 18 Years and older - Genders Eligible for Study:Both - Histological or cytological proof of component (any percent) of clear cell RCC (renal cell carcinoma). - Metastatic or locally advanced unresectable RCC. NOTE: Prior nephrectomy is not mandatory. - Progressive disease after 1-2 prior VEGF-directed tyrosine kinase inhibitors (TKIs). - Measurable disease according to RECIST and obtained by imaging within 30 days prior to registration for protocol therapy. - Written informed consent and HIPAA authorization for release of personal health information. - Age > 18 years at the time of consent. - Females of childbearing potential and males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 4 weeks after treatment discontinuation. - Females of childbearing potential must have a negative pregnancy test within 7 days prior to registration for protocol therapy. Other eligibility criteria may apply. - No active brain metastases. Patients with neurological symptoms must undergo a head CT scan or brain MRI to exclude brain metastasis within 30 days prior to registration on protocol therapy. NOTE: A patient with prior brain metastasis are eligible if they have completed their radiation treatment for brain metastasis =30 days prior to registration for protocol therapy, are off steroids, and are asymptomatic. - No other currently active malignancy. - No treatment with any investigational agent within 14 days prior to registration for protocol therapy. NOTE: If treated with investigational agent within 14 days prior to registration, AE must be resolved back to baseline. - Prior cancer treatment must be completed at least 14 days prior to registration for protocol therapy and the patient must have recovered from the acute toxic effects of the regimen. With the exception of Bevacizumab treatment, which must be completed 30 days prior to registration for protocol therapy. - Prior radiation therapy to < 25% of the bone marrow [see bone marrow radiation chart in the study procedure manual (SPM)] allowed if completed within 30 days prior to registration for protocol therapy. - Corrected QT interval (QTc) = 450 msec at least 7 days prior to registration for protocol therapy. - No clinically significant infections as judged by the treating investigator. - No liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis. - No collecting duct, medullary or sarcomatoid histology. - No prior treatment with temsirolimus or everolimus in the phase II component of the study. NOTE: Prior treatment with these agents is permitted in the phase I component of the study. - No use of full dose, therapeutic anti-coagulation with warfarin or related anti-coagulants or unfractionated or low molecular weight heparins. - No uncontrolled hypertension (BP >150/100mmHg despite full doses of 1 anti-hypertensive medication). - No thrombotic event within 6 months (deep vein thrombosis, pulmonary embolism) of registration for protocol therapy. - No grade 2 or greater peripheral neuropathy. Other exclusion criteria may apply. 1cb31f54494bb521641e06b2ad5faf82 8785 Anti-CXCR4 (BMS-936564) Alone and in Combination With Lenalidomide/Dexamethasone or Bortezomib/Dexamethasone in Relapsed/Refractory Multiple Myeloma I Pamela Becker, MD, PhD 20111816 36; 57 Hematologic Malignancies; Multiple Myeloma (MM) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8785.html http://www.clinicaltrials.gov/ct/search?term=NCT01359657 NCT01359657 The purpose of this study is to determine 1) the safety and tolerability of multiple intravenous doses of anti-CXCR4 (BMS-936564) as monotherapy and as combination, and 2) the maximum tolerated dose (MTD) of BMS-936564 in combination with Lenalidomide/Dexamethasone or Bortezomib/Dexamethasone in subjects with relapsed or refractory multiple myeloma. - Ages Eligible for Study: 18 Years and older - Genders Eligible for Study: Both - Subjects must have confirmed diagnosis of multiple myeloma with measurable disease Excluded are subjects with only plasmacytomas, plasma cell leukemia, or non-secretory myeloma. - Disease must be assessed within 28 days prior to treatment initiation. - Subjects must have evidence of relapsed or relapsed/refractory disease. - Subjects must have received at least 2 prior regimens for multiple myeloma. - Eastern Cooperative Oncology Group (ECOG) Performance Status 0 - 2. - Subjects must have received last treatment (ie, chemotherapy, radiotherapy, biological, immunotherapy or investigational agent [therapeutic or diagnostic]) at least 14 days prior to treatment initiation. Other eligibility criteria may apply. - A serious uncontrolled medical disorder or active infection. - Current or recent (within 3 months) gastrointestinal disease or condition that could impact the absorption of orally-administered drug. - Inability to swallow oral medication. - Uncontrolled or significant heart disease. - Any other malignancy, excluding basal or squamous cell carcinoma of the skin, cervical carcinoma in situ, localized prostate cancer, or superficial bladder cancer stage 0, from which the subject has not been disease-free for at least 3 years. Other exclusion criteria may apply. 55ca82eafd0cba3594f8ed8ac1f37e9c 9009 The BEACON Study (Breast Cancer Outcomes With NKTR-102) III Jennifer Specht, MD 20111824 13; 83 Breast Cancer; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9009.html http://www.clinicaltrials.gov/ct/search?term=NCT01492101 NCT01492101 The study is designed as an open-label, randomized, parallel, two arm, multicenter, international Phase 3 study in patients with recurrent or metastatic breast cancer previously treated with cytotoxic chemotherapy regimens. The primary study objective is to compare overall survival of patients who receive NKTR-102 given once every 21 days to patients who receive treatment of Physician's Choice selected from a list of seven single-agent intravenous therapies. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Female - Patient is an adult female with histologically or cytologically confirmed carcinoma of the breast for whom single-agent cytotoxic chemotherapy is indicated - Patient can have either measurable or non-measurable disease by RECIST. - Patient has received prior therapy (administered in the neoadjuvant, adjuvant and/or metastatic setting) with an anthracycline, a taxane and capecitabine - Patient has minimum of 2 and a maximum of 5 prior cytotoxic chemotherapy regimens with the last dose administered within 6 months. A minimum of two chemotherapy regimens had to be for locally recurrent and/or metastatic disease. All therapy received prior to a diagnosis of metastatic disease (eg, neoadjuvant, adjuvant or repeated adjuvant therapy following a second resection) is counted as one regimen. - Patient has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. - Adequate hematopoietic, liver and kidney functions. Other eligibility criteria may apply. - Patient with chemotherapy within 21 days, radiotherapy within 14 days, biological therapy with 14 days, hormonal therapy within 7 days and investigational therapy within 21 days prior to randomization. - Patient with any major surgery within 28 days prior to randomization. - Patient with concurrent use of biologic agents for the treatment of cancer including antibodies or any investigational agent(s). - Patient with prior treatment for cancer with a camptothecin derivative. - Patient with chronic or acute GI disorders resulting in diarrhea of any severity grade; patients who are using chronic anti-diarrheal supportive care to control diarrhea in the 28 days prior to randomization. - Patient received pharmacotherapy for hepatitis B or C, tuberculosis or HIV. - Patient with known cirrhosis diagnosed with Child-PUGH Class A or higher liver disease. - Patient with prior malignancy (other than breast cancer) except for non-melanoma skin cancer and carcinoma in situ (of the cervix or bladder), unless diagnosed and definitively treated more than 5 years prior to randomization. - Patient requiring daily use of oxygen supplementation in the 28 days prior to randomization. - Patients with significant cardiovascular impairment. Other exclusion criteria may apply. a4e5c74991eaa0d648958cfae8a04fbb 8969 Safety Study of IL-21/Ipilimumab Combination in the Treatment of Melanoma I Shailender Bhatia, MD 20111942 24; 52; 81; 83 Eye Cancer; Melanoma; Skin Cancer; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8969.html http://www.clinicaltrials.gov/ct/search?term=NCT01489059 NCT01489059 The purpose of this study is to determine whether the combination of interleukin-21 (IL-21) and Ipilimumab in subjects with melanoma is safe, and provide preliminary information on the clinical benefits of the combination compared with Ipilimumab alone - Ages Eligible for Study: 18 Years and older - Genders Eligible for Study: Both - Unresectable Stage III or Stage IV melanoma - Part 1 Dose Escalation: Prior melanoma treatment allowed except for the following: ipilimumab, BMS-982470 (rIL-21), anti-Programmed Death-1 (anti-PD-1), anti-programmed death-ligand 1 (anti-PD-L1), anti-PD-L2 or anti-CD137 - Part 2 Cohort expansion: Prior treatment for melanoma is not allowed, except for adjuvant therapy with interferon alpha or melanoma vaccines which are permitted - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 - Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) - Normal liver function tests Other eligibility criteria may apply. - Part 1 Dose escalation: subjects with = 2 brain metastases of stable size, = 4 weeks post-radiation treatment, and off steroids are allowed - Part 2 Cohort expansion: subjects with known or suspected brain metastases and uveal melanoma are excluded - Autoimmune disease Other exclusion criteria may apply. ae70044ac3f2bed86fc890c57ca59bb0 9366 Study to Learn if Two Doses of a Test Drug (Fostamatinib) Helps People With Large B-Cell Lymphoma,a Type of Blood Cancer II Andrei Shustov, MD 20111975 36; 48; 64 Hematologic Malignancies; Lymphoma; Non-Hodgkin's Lymphoma (NHL) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9366.html http://www.clinicaltrials.gov/ct/search?term=NCT01499303 NCT01499303 This study will evaluate the effectiveness of two doses of fostamatinib (100 mg twice a day and 200 mg twice a day) in patients with worsening or unmanageable lymphoma with a specific type of lymphoma called Diffuse Large B-Cell Lymphoma (abbreviated as DLBCL) Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Aged at least 18 years of age. - Patients with relapsed or refractory diffuse large B-cell lymphoma who have previously received R-CHOP (or equivalent) chemo-immunotherapy and high dose chemotherapy with stem cell rescue, or who are ineligible for high dose therapy with stem cell rescue. - Measurable disease as defined by Cheson et al 2007 criteria. - One fresh pre-treatment excisional or core needle biopsy from suitable and accessible site. - World Health Organization (WHO) performance status 0 to 1. Other eligibility criteria may apply. - Treatment with nitrosurea, mitomycin C, investigational agents or study drugs w/in28 days of first dose of study treatment, any other chemotherapy, immunotherapy or anticancer agents w/in 3 weeks of first dose of study treatment, previous fostamatinib. - With the exception of alopecia, any unresolved toxicities from prior therapy or surgery greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1. - Uncontrolled hypertension (defined as >140mmHg systolic and/or > 90 mmHG diastolic at baseline with or without antihypertensive therapy. - Evidence of tuberculosis (TB). - Inadequate bone marrow reserve. Other exclusion criteria may apply. 4976d7f52f6c55410e61f7e83d7d6b82 9003 A Study of Onartuzumab (MetMAb) Versus Placebo in Combination With Paclitaxel Plus Platinum in Patients With Squamous Non-Small Cell Lung Cancer II Keith Eaton, MD, PhD 20111995 46; 83 Lung Cancer; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9003.html http://www.clinicaltrials.gov/ct/search?term=NCT01519804 NCT01519804 This multicenter, randomized, double-blind, placebo-controlled study will evaluate the efficacy and safety of onartuzumab (MetMAb) in combination with paclitaxel plus platinum in patients with incurable Stage IIIB or Stage IV squamous non-small cell lung cancer (NSCLC). Patients will be randomized to receive either onartuzumab (MetMAb) 15 mg/kg iv or placebo on Day 1 of each 21-day cycle in combination with 4 cycles of paclitaxel 200 mg/m2 iv and platinum (carboplatin/cisplatin) iv on Day 1 of each 21-day cycle. Patients who have not progressed after 4 cycles will continue with either onartuzumab (MetMAb) or placebo as maintenance therapy until disease progression or unacceptable toxicity occurs. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Adult patients, >/= 18 years of age - Histologically or cytologically confirmed Stage III B or Stage IV squamous non-small cell lung cancer (NSCLC) - Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 - No prior chemotherapy for squamous NSCLC - Adequate tissue for central IHC assay of Met receptor, and EGFR testing if EGFR status is unknown - Radiographic evidence of disease Other eligibility criteria may apply. - Prior systemic treatment for Stage IIIB or IV squamous NSCLC - NSCLC with histology classified as adenocarcinoma, large cell, mixed adenosquamous, or NSCLC not otherwise specified (NOS) - Prior exposure to experimental treatment targeting either the HGF or Met pathway - Patients with tumors confirmed to have EGFR-activating mutations who are suitable for anti-EGFR therapy (e.g. gefitinib or erlotinib), as determined by the investigator - Uncontrolled brain metastases and treatment by neurosurgical resection or brain biopsy within 4 weeks prior to Day 1 of Cycle 1 - History of another malignancy in the previous 3 years except for prior history of in situ cancer or basal or squamous cell skin cancer - Pregnant or lactating women - Uncontrolled diabetes - Impaired bone marrow, liver or renal function as defined by protocol - Significant history of cardiovascular disease - Positive for HIV infection Other exclusion criteria may apply. dfb8e0192bbf9bae91ad56938eb33e44 9004 A Study of Onartuzumab (MetMAb) in Combination With Bevacizumab (Avastin) Plus Platinum And Paclitaxel or With Pemetrexed Plus Platinum in Patients With Non-Squamous Non-Small Cell Lung Cancer II Keith Eaton, MD, PhD 20111997 46; 83 Lung Cancer; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9004.html http://www.clinicaltrials.gov/ct/search?term=NCT01496742 NCT01496742 This multicenter, randomized, double-blind, placebo-controlled study will evaluate the efficacy and safety of RO5490258 (MetMab) in combination with either of two backbone chemotherapy regimens in the first-line setting in patients with incurable Stage IIIB or IV non-squamous non-small cell lung cancer. In Cohort 1, patients will be randomized to receive 4 cycles of bevacizumab (Avastin) 15 mg/kg iv, paclitaxel 200 mg/m2 iv, platinum (cisplatin/carboplatin) iv plus either MetMab 15 mg/kg iv or placebo on Day 1 of each 21-day cycle. In Cohort 2, patients will be randomized to receive pemetrexed 500 mg/m2 iv, platinum (cisplatin/carboplatin) iv plus either MetMAb 15 mg/m2 iv or placebo on Day 1 of each 21-day cycle. Patients who have not progressed after 4 cycles will be offered maintenance therapy with their assigned treatment of bevacizumab plus either MetMAb or placebo (Cohort 1) or pemetrexed plus either MetMAb or placebo (Cohort 2). Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs. - Ages Eligible for Study: 18 Years and older - Genders Eligible for Study: Both - Adult patients, >/= 18 years of age - Histologically or cytologically confirmed Stage IIIB or Stage IV non-squamous non-small cell lung cancer (NSCLC) - Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 - For patients who received prior adjuvant chemotherapy: a treatment-free interval of at least 12 months since last chemotherapy cycle - Adequate tissue for central IHC assay of Met receptor, and EGFR testing if EGFR status is unknown - Radiographic evidence of disease Other eligibility criteria may apply. - Prior systemic treatment for Stage IIIB or IV non-squamous NSCLC - Evidence of mixed NSCLC with a predominance of the squamous cell type - Prior exposure to experimental treatment targeting either the HGF or Met pathway - Patients with tumors confirmed to have EGFR-activating mutations who are suitable for anti-EGFR therapy (e.g. gefitinib or erlotinib), as determined by the investigator - Known central nervous system (CNS) disease, other than stable, treated brain metastases - History of another malignancy in the previous 3 years, except for history of in situ cancer or basal or squamous cell skin cancer - Uncontrolled diabetes - Pregnant or lactating women - Impaired bone marrow, liver or renal function (as defined by protocol) - Significant history of cardiovascular disease - Positive for HIV infection Other exclusion criteria may apply. 1f3740d5ed8e96f9bce2f03becbb883b 8978 A Phase 3 Study to Evaluate Marqibo® in the Treatment of Subjects =/> 60 Years Old With Newly Diagnosed ALL III Andrei Shustov, MD 20112071 1; 36 Acute Lymphoid Leukemia (ALL); Hematologic Malignancies Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8978.html http://www.clinicaltrials.gov/ct/search?term=NCT01439347 NCT01439347 A phase 3 study in the treatment of subjects >or= 60 years old with newly diagnosed acute lymphoblastic leukemia (ALL). Ages Eligible for Study: 60 Years and older Genders Eligible for Study: Both - Have provided written, signed, and dated informed consent to participate in the study, in accordance with the ICH GCP Guideline E6 and all applicable local regulations.Are age >or=60 years (at the time of providing informed consent). - Have newly diagnosed, histologically proven, untreated Philadelphia chromosome-negative (Ph-) ALL, with >or= 5% bone marrow blasts. - Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. Have a life expectancy >or= 3 months. - Have renal and liver function as defined below within 14 days, inclusive, prior to study enrollment, unless the abnormality is considered attributable to leukemia: --- Total bilirubin =/< 2.0 x the upper limit of normal (ULN), unless the subject has a known diagnosis of Gilbert's disease Aspartate transaminase (AST, SGOT) or alanine transaminase (ALT, SGPT) =/< 3 x ULN Serum creatinine =/< 1.5 x ULN. Not have had major surgery within 4 weeks before the planned start of treatment. - If female, are post-menopausal, surgically sterilized, or willing to use acceptable methods of birth control (eg, hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) from the screening visit through 30 days after the last dose of any protocol defined chemotherapeutic agents. - If male and sexually active with a partner of child-bearing potential, agree to use an acceptable barrier method for contraception from the screening visit through 30 days after the last dose of any protocol defined chemotherapeutic agents. - Have the ability and willingness to fully comply with study procedures and restrictions. Other eligibility criteria may apply. - Has had prior systemic chemotherapy (for ALL or other malignancy). Has had prior vincristine for any reason. Is planning to undergo stem cell transplantation (SCT) as any part of first-line therapy for ALL. - Has Burkitt's lymphoma/leukemia. Has Philadelphia chromosome-positive (Ph+) ALL and/or BCR/ABL rearrangements documented by fluorescent in-situ hybridization (FISH), cytogenetics, or polymerase chain reaction (PCR). - Has active central nervous system (CNS) disease. Has ongoing neuropathy of any etiology > Grade 1. Has a history of persistent active neurologic disorders including demyelinating form of Charcot-Marie-Tooth syndrome, acquired demyelinating disorders, and other demyelinating conditions. - Prior hydroxyurea (Hydrea®) for the management of any condition other than leukocytosis or prior hydroxyurea of >7 days duration for the management of leukocytosis (hydroxyurea for the management of leukocytosis must be planned to be tapered off before or on Day 5 of Induction). - Has received prior steroids within 7 days before beginning protocol-specified Induction therapy for reasons other than leukocytosis (steroids for the management of leukocytosis are allowed but must be planned to be tapered off before or on Day 5 of Induction). - Has an active serious infection not controlled by oral or IV antibiotics or antifungals. - Has received any investigational therapy within 28 days before beginning any protocol-defined chemotherapeutic treatment. Other exclusion criteria may apply. 1d273e91cd17294f4bcb2ef84e42e6ea 8850 A Phase 2 Study Comparing Chemotherapy in Combination With OGX-427 or Placebo in Patients With Bladder Cancer II Evan Yu, MD 20120003 30; 83; 124 Genitourinary Cancer; Solid Tumors; Transitional Cell Carcinoma (TCC) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8850.html http://www.clinicaltrials.gov/ct/search?term=NCT01454089 NCT01454089 This study evaluates the safety and efficacy of standard chemotherapy in combination with the investigational drug OGX-427 in patients with advanced bladder cancer. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Age 18 years and older at the time of consent - Histologically documented metastatic or locally inoperable advanced TCC of the urinary tract (bladder, urethra, ureter and renal pelvis) (T4b, N2, N3 or M1 disease) NOTE: Certain mixed histologies that are predominately (> or = to 50%) TCC are eligible: squamous, adenocarcinoma, and undifferentiated. Mixed undifferentiated histology requires IHC consistent with a TCC origin. Mixed small-cell histologies are excluded. - Measurable disease defined as at least one target lesion that has not been irradiated and can be accurately measured in at least one dimension by RECIST 1.1 criteria - No prior systemic chemotherapy with the following exceptions: - 1) Prior use of radiosensitizing single agent therapy is allowed - 2) Prior neoadjuvant and adjuvant chemotherapy may be allowed - Minimum of 21 days since prior major surgery or radiation therapy - Karnofsky performance status > or = to 70% - Required laboratory values at baseline: - 1) ANC > or = to 1.5x1^9 cells/L - 2) platelet count > or = to 125 x 1^9/ - 3) Calculated creatinine clearance > or = to 60 mL/minute - 4) bilirubin < or = to 1.5 x ULN (< or = to 2.5 x ULN if secondary to Gilbert's disease) - 5) AST and ALT < or = to 3.0 x ULN - If of child-bearing potential, willing to use contraceptives - Willing to give written informed consent Other eligibility criteria may apply. - A candidate for potential curative surgery or radiotherapy - Intravesical therapy within the last 3 months - Documented brain metastasis or carcinomatous meningitis, treated or untreated. NOTE: Brain imaging is not required unless the patient has symptoms or physical signs of CNS disease. - Peripheral neuropathy > or = to Grade 2 - Known serious hypersensitivity to gemcitabine, cisplatin or carboplatin - Current serious, uncontrolled medical condition such as congestive heart failure, angina, hypertension, arrhythmia, diabetes mellitus, infection, etc. or any condition such as a psychiatric illness which in the opinion of the investigator would make the patient unacceptable for the protocol - Cerebrovascular accident, myocardial infarction or pulmonary embolus within 6 months of randomization - Active second malignancy (except non-melanomatous skin cancer): active secondary malignancy is defined as a current need for cancer therapy or a high possibility (>30%) of recurrence during the study - Pregnant or nursing (must have a negative serum or urine pregnancy test within 72 hours prior to randomization) - Participating in a concurrent clinical trial of an experimental drug, vaccine or device. Participation in an observational study is allowed. Other exclusion criteria may apply. 6a27f348993c87ca62c76205358a050c 9080 ADI-PEG 20 Versus Placebo in Subjects With Advanced Hepatocellular Carcinoma Who Have Failed Prior Systemic Therapy III William Harris 20120106 45; 83 Liver Cancer; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9080.html http://www.clinicaltrials.gov/ct/search?term=NCT01287585 NCT01287585 This is a study of ADI-PEG 20 (pegylated arginine deiminase), an arginine degrading enzyme versus placebo in patients with hepatocellular carcinoma who have failed prior systemic treatment (chemotherapy). Hepatocellular carcinomas have been found to require arginine, an amino acid. Thus the hypothesis is that by restricting arginine with ADI-PEG 20, the hepatocellular carcinoma cells will starve and die. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Prior diagnosis of HCC confirmed histologically. - Prior treatment with at least 1 systemic agent, with documented progressive disease after systemic agent(s), or adverse event(s)associated with prior systemic agent(s) that resulted in discontinuance of that agent(s). - Cirrhotic status of Child-Pugh grade B7. - Expected survival of at least 3 months. - Adequate hematologic, hepatic, and renal function. Other eligibility criteria may apply. - Candidate for potential curative therapies (i.e., resection or transplantation) or loco-regional approaches (i.e., ablation, embolization). - Significant cardiac disease. - Serious infection requiring treatment with systemically administered antibiotics. - Pregnancy or lactation. - Expected non-compliance. - Uncontrolled intercurrent illness, or psychiatric illness or social situations that would limit compliance with study requirements. - Subjects who have had any anticancer treatment within 2 weeks prior to entering the study. - Subjects who have not fully recovered from toxicities associated with previous HCC loco-regional or systemic therapies. - Subjects with history of another primary cancer, with the exception of: a) curatively resected non-melanoma skin cancer; b) curatively treated cervical carcinoma in situ; or c) other primary solid tumor with no known active disease present in the opinion of the investigator will not affect patient outcome in the setting of current HCC diagnosis. - Allergy to pegylated products. - Bleeding esophageal or gastric varices within the prior three months, except if banded or treated. - Subjects known to be HIV positive. - Uncontrolled ascites (defined as not easily controlled with diuretic treatment). - Having received any blood transfusion, blood component preparation, erythropoietin, albumin preparation, or granulocyte colony stimulating factors (G-CSF) within 7 days prior to screening laboratories or after screening laboratories have been obtained until first dose of study drug or placebo. - Use of traditional medicines approved by local authorities, including but not limited to Chinese herbs within 14 days of first dose of study drug or placebo. - ECOG performance status > 2. - Prior allograft,including liver transplant. Other exclusion criteria may apply. 3d53f584891592564bad928c291e26ca 9165 Alisertib (MLN8237) or Investigator's Choice in Patients With Relapsed/Refractory Peripheral T-Cell Lymphoma III Andrei Shustov, MD 20120291 36; 48; 49; 64 Hematologic Malignancies; Lymphoma; Lymphoproliferative Disease; Non-Hodgkin's Lymphoma (NHL) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9165.html http://www.clinicaltrials.gov/ct/search?term=NCT01482962 NCT01482962 This is a phase 3, randomized, 2-arm, open-label, international trial evaluating alisertib compared with single-agent treatment, as selected by the investigator from the offered options of pralatrexate or gemcitabine or romidepsin, in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). Note: romidepsin will not be used as a single-agent comparator in countries that do not permit its use at this time. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Male or female patients age 18 or older - Patients with PTCL according to World Health Organization (WHO) criteria and have relapsed or are refractory to at least 1 prior systemic, cytoxic therapy for PTCL. Patients must have received conventional therapy as a prior therapy. Cutaneous-only disease is no permitted. Patients must have documented evidence of progressive disease. - Tumor biopsy available for central hematopathologic review - Measurable disease according to the IWG criteria - Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 - Female patients who are post menopausal for at least 1 year, surgically sterile, or agree to practice 2 effective methods of contraception through 30 days after the last dose of study drug or agree to abstain from heterosexual intercourse. - Male patients who agree to practice effective barrier contraception through 6 months after the last dose of alisertib or agree to abstain from heterosexual intercourse - Suitable venous access - Voluntary written consent Other eligibility criteria may apply. - Known central nervous system lymphoma - Systemic antineoplastic therapy, immunotherapy, investigational agent or radiation therapy within 4 weeks of first dose of study treatment or concomitant use during study - Prior administration of an Aurora A kinase-targeted agent, including alisertib; or all of the 3 comparator drugs (pralatrexate, or romidepsin or gemcitabine; or known hypersensitivity) - History of uncontrolled sleep apnea syndrome or other conditions that could result in excessive daytime sleepiness - Cardiac condition as specified in study protocol, including left ventricular ejection fraction (LVEF) <40% - Concomitant use of other medicines as specified in study protocol - Patients with abnormal gastric or bowel function who require continuous treatment with H2-receptor antagonists or proton pump inhibitors - Known active infection with human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C - Autologous stem cell transplant less than 3 months prior to enrollment - Patients who have undergone allogeneic stem cell or organ transplantation any time - Inadequate blood levels, bone marrow or other organ function as specified in study protocol - The patient must have recovered to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade = /<1 toxicity, to patients's baseline status (except alopecia), or deemed irreversible from the effects of prior cancer therapy - Major surgery, serious infection, or infection requiring systemic antibiotic therapy within 14 days prior to the first dose of study treatment - Female patients who are breastfeeding or pregnant - Coexistent second malignancy or history of prior solid organ malignancy within previous 3 years - Serious medical or psychiatric illness or laboratory abnormality that could, in the investigator's opinion, potentially interfere with the completion of treatment according to the protocol Other exclusion criteria may apply. ddf033a8cc93e7ce13ce9364580637da 9195 Safety Study of IL-21/Anti-PD-1 Combination in the Treatment of Solid Tumors I Laura Chow 20120892 83 Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9195.html http://www.clinicaltrials.gov/ct/search?term=NCT01629758 NCT01629758 The purpose of this study is to determine whether the combination of the 2 drugs being investigated (IL-21 and anti-PD-1) is safe, and provide preliminary information on the clinical benefits of two different schedules of the combination. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - All subjects will have locally advanced or metastatic cancer resistant to standard treatment, for which no additional standard treatment is available, or for which the subject declines standard treatment, excluding cancer in the blood; in Part 2 (Cohort Expansion), tumor types will be further restricted to clear cell renal cell carcinoma or non-small cell lung cancer - At least 1 non-irradiated lesion with measurable disease at baseline - Availability of an existing tumor biopsy sample (or consent to allow pre-treatment tumor biopsy if sample not available) Other eligibility criteria may apply. - Uncontrolled brain metastases - Certain prior drug treatments for the cancer - Autoimmune disease - Inadequate liver or kidney function Other exclusion criteria may apply. 2be5a62b1ce934706b1f9df5f673371b 9248 Safety and Efficacy Study of Enzalutamide Versus Bicalutamide in Men With Prostate Cancer (STRIVE) II Tia Higano, MD 20120956 71; 83 Prostate Cancer; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9248.html http://www.clinicaltrials.gov/ct/search?term=NCT01664923 NCT01664923 The purpose of this study is to determine the safety and efficacy of enzalutamide vs. bicalutamide in asymptomatic or mildly symptomatic patients with prostate cancer who have disease progression despite primary androgen deprivation therapy. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Male - Males age 18 or older; - Histologically or cytologically confirmed adenocarcinoma of the prostate; - Ongoing androgen deprivation therapy - Serum testosterone level =< 50 ng/dL (1.73 nmol/L) at the Screening visit; - Progressive disease at study entry defined by PSA progression and/or radiographic progression that occurred while the patient was on primary androgen deprivation therapy - Asymptomatic or mildly symptomatic from prostate cancer; - Eastern Cooperative Oncology Group (ECOG) performance status of 0-1; - Estimated life expectancy of => 12 months; - Able to swallow the study drug and comply with study requirements. Other eligibility criteria may apply. - Severe concurrent disease, infection, or co-morbidity; - Known or suspected brain metastasis or active leptomeningeal disease; - History of another invasive malignancy within the previous 5 years other than curatively treated non-melanomatous skin cancer and American Joint Committee on Cancer (AJCC) Stage 0 or Stage 1 cancers that have a remote probability of recurrence; - Absolute neutrophil count < 1,500/µL, or platelet count < 100,000/µL, or hemoglobin < 9 g/dL at the Screening visit; - Total bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 times the upper limit of normal (ULN) at the Screening visit; - Creatinine > 2 mg/dL at the Screening visit; - Albumin < 3.0 g/dL at the Screening visit; - History of seizure or any condition that may predispose to seizure; - Clinically significant cardiovascular disease; - Gastrointestinal disorder affecting absorption (e.g., gastrectomy, active peptic ulcer disease within last 3 months); - Major surgery within 4 weeks of enrollment; - Use of opiate analgesics for pain from prostate cancer within 4 weeks of enrollment; - Radiation therapy for treatment of the primary tumor within 3 weeks of enrollment; - Prior ketoconazole, abiraterone, or cytotoxic chemotherapy for prostate cancer; - Use of antiandrogens within 4 weeks prior to enrollment; - Prior disease progression, as assessed by the Investigator, while receiving bicalutamide; - Participation in a previous clinical trial of enzalutamide or an investigational agent that inhibits the androgen receptor or androgen synthesis (patients who received placebo are acceptable); - Use of an investigational agent within 4 weeks of enrollment; - Use of herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease PSA levels (e.g., saw palmetto) or systemic corticosteroids for prostate cancer within 4 weeks of enrollment; - Any condition or reason that, in the opinion of the Investigator, interferes with the ability of the patient to participate in the trial, which places the patient at undue risk, or complicates the interpretation of safety data. Other exclusion criteria may apply. 025e27cf28bf88f65b504b1442133de6 9170 A Dose-finding Study of a Combination of Imatinib and BKM120 in the Treatment of 3rd Line GIST Patients I Robin Jones 20121008 28; 83 Gastrointestinal Cancer; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9170.html http://www.clinicaltrials.gov/ct/search?term=NCT01468688 NCT01468688 The purpose of this study is to determine a maximum tolerated dose and/or recommended phase 2 dose of a combination of imatinib and BKM120 in the treatment of 3rd line GIST patients. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - 1.Male or female patients =/> 18 years of age - 2.WHO performance status (PS) of 0-2 - 3.Histologically confirmed diagnosis of GIST that is unresectable or metastatic - 4.Available tissue specimen: ---- Dose-escalation cohorts: patients must have available archival tumor tissue which can be shipped during the course of the study ---- Dose-expansion cohort: patients must have available archival tumor tissue which can be shipped during the course of the study and must agree to a fresh pre-treatment biopsy. - 5.Failed prior therapy with imatinib followed by sunitinib for the treatment of unresectable or metastatic GIST. Note the following specific criteria for the two phases of the trial: ---- Dose-escalation cohorts: patients who failed prior therapy with imatinib and then have failed therapy with sunitinib. Treatment failure may be due to either disease progression on therapy (both imatinib and sunitinib) or intolerance to therapy (sunitinib). Dose-escalation cohort patients may have had additional lines of therapy not limited to imatinib and sunitinib. ---- Dose-expansion cohort: patients must have documented disease progression on both imatinib and sunitinib. In addition, patients may have had no more than two lines of prior therapy (i.e. treatment with imatinib followed by treatment with sunitinib). ---- Adjuvant imatinib will not count as a prior course of imatinib for the purposes of this criterion Other eligibility criteria may apply. - 1.Previous treatment with PI3-K inhibitors - 2.A medical history of any of the following mood disorders as judged by the Investigator or a psychiatrist: ---- Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or thoughts, or homicidal thoughts (immediate risk of doing harm to others) ---- =/> CTCAE grade 3 anxiety - 3.When completing the patient questionnaires at screening: ---- Meets the cut-off score of =/>10 in the nine item depression scale of the Patient Health Questionnaire (PHQ-9) or a cut-off of =/> 15 in the Generalized Anxiety Disorder Assessment (GAD 7) mood scale respectively, or ---- Selects positive response of 1, 2, 3 to question number 9 regarding potential for suicidal thoughts or ideation in the PHQ-9 (independent of the total score of the PHQ-9) - 4.Severe and/or uncontrolled concurrent medical condition that, in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol (e.g. acute or chronic liver, pancreatic, severe renal disease considered unrelated to study disease, chronic pulmonary disease including dyspnea at rest from any cause). - 5.Poorly controlled diabetes mellitus (defined as HbA1c > 8%) Other protocol-defined inclusion/exclusion criteria may apply. Other exclusion criteria may apply. 0b43c5f575b1307c1596ac231986e8e9 9480 A Study of MEHD7945A + FOLFIRI Versus Cetuximab + FOLFIRI in Second Line in Patients With KRAS Wild-Type Metastatic Colorectal Cancer II Andrew Coveler, MD 20121026 73; 83 Rectal Cancer; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9480.html http://www.clinicaltrials.gov/ct/search?term=NCT01652482 NCT01652482 This open-label, randomized, multicenter Phase II study will evaluate the safety and efficacy of MEHD7945A when combined with FOLFIRI chemotherapy as compared to cetuximab plus FOLFIRI in patients with KRAS wild-type metastatic colorectal cancer who have progressed after first-line oxaliplatin-containing chemotherapy for metastatic disease. Patients will be randomized to receive FOLFIRI chemotherapy plus either MEHD7945A (1100 mg intravenously every 2 weeks) or cetuximab (400mg/m2 iv loading dose Day 1 Cycle 1, followed by 250 mg/m2 iv every week). Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Adult patients, >/= 18 years of age - Histologically or cytologically confirmed adenocarcinoma of the colon and/or rectum, with KRAS wild-type status - Progressive disease on or after first-line oxaliplatin-containing regimen for metastatic colorectal cancer; patients must have received oxaliplatin-containing chemotherapy for >/= 3 months; no more than one prior chemotherapy for metastatic disease is allowed - Measurable disease per RECIST v1.1 - Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 - Adequate hematologic and end-organ function Other eligibility criteria may apply. - Prior treatment with irinotecan - Prior treatment with an investigational or approved HER-targeted agent - Last anti-tumor therapy within 4 weeks prior to Cycle 1, Day 1, including chemotherapy, biologic, experimental, hormonal or radiotherapy, or not having recovered from all treatment-related toxicities (except for alopecia) to Grade </=1, with the following exceptions: oxaliplatin-containing chemotherapy within 2 weeks prior to Cycle 1, Day 1, oxaliplatin-related neuropathy that is Grade </= 2 and considered stable, and palliative radiotherapy to bone metastases within 2 weeks prior to Cycle 1, Day 1 - Leptomeningeal disease as the only manifestation of the current malignancy - Active infection requiring IV antibiotics - Active autoimmune disease that is not controlled by nonsteroidal anti-inflammatory drugs - Current severe , uncontrolled systemic disease - History of cardiac heart failure or serious cardiac arrhythmia requiring treatment (except for atrial fibrillation and paroxysmal supraventricular tachycardia) - History of myocardial infarction within 6 months prior to Cycle 1 Day 1, or history of unstable angina - Clinically significant GI bleeding within 6 months prior to Cycle 1 Day 1 - History of severe (Grade 3 or 4) allergic or hypersensitivity reaction to therapeutic antibodies that required discontinuation of treatment - Known HIV infection - Untreated CNS metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control) - Pregnant or lactating women - Malignancies other than colorectal cancer within 5 years prior to randomization, except for adequately treated basal or squamous cell skin cancer and carcinoma in situ of the cervix Other exclusion criteria may apply. 47364eeac107327b5e4ccd5785d4a9d2 9053 A Study of the Safety and Pharmacokinetics of Escalating Doses of DSTP3086S in Patients With Metastatic Castration-Resistant Prostate Cancer I Tia Higano, MD 20121064 71; 83 Prostate Cancer; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9053.html http://www.clinicaltrials.gov/ct/search?term=NCT01283373 NCT01283373 This is a Phase I, multicenter, open-label, dose-escalation study of DSTP3086S administered as a single agent by intravenous (IV) infusion to patients with metastatic Castration-Resistant Prostate Cancer (CRPC). Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Male - Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 - Life expectancy of at least 12 weeks - Histologic documentation of adenocarcinoma of the prostate - Surgical castration or ongoing use of gonadotropin-releasing hormone agonists with confirmed castrate levels of testosterone - Metastatic progressive CRPC defined as progressive disease despite surgical castration or ongoing use of gonadotropin-releasing hormone agonists with confirmed castrate levels of testosterone - For patients in the dose-expansion cohort of the study, not more than two prior lines of cytotoxic chemotherapy in the metastatic setting - Evaluable or measurable disease - Documented willingness to use an effective means of contraception Other eligibility criteria may apply. - Anti-tumor therapy, including chemotherapy, biologic, experimental, or hormonal therapy, or radiotherapy within 4 weeks prior to Day 1, with the following exceptions: maintenance hormonal therapy for metastatic prostate cancer and palliative radiation to bone metastases within 2 weeks prior to Day 1 - Major surgical procedure within 4 weeks prior to Day 1 - Known active bacterial, viral, fungal, mycobacterial, or other infection (including HIV and atypical mycobacterial disease, but excluding fungal infections of the nail beds) - Ongoing corticosteroid use with > 10 mg of daily prednisone or equivalent - Symptomatic hypercalcemia requiring continued use of bisphosphonate therapy. Patients who are receiving bisphosphonate therapy specifically to prevent skeletal events and who do not have a history of clinically significant hypercalcemia are eligible. - History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins) - Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis - Untreated or active central nervous system (CNS) metastases. Patients with a history of treated CNS metastases are eligible, provided that they meet all of the following criteria: evaluable or measurable disease outside the CNS, radiographic demonstration of improvement upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study, and screening CNS radiographic study is >/= 8 weeks since completion of radiotherapy and >/= 4 weeks since the discontinuation of corticosteroids and anticonvulsants Other exclusion criteria may apply. 9092ce5612edc66099e76dfb4af803c1 9180 A Phase 1b Study of SGN-75 in Combination With Everolimus in Patients With Renal Cell Carcinoma I John Thompson, MD 20121070 41; 74 Kidney Cancer; Renal Cancer Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9180.html http://www.clinicaltrials.gov/ct/search?term=NCT01677390 NCT01677390 This is a phase 1, open-label, dose-escalation clinical trial to evaluate the safety of SGN-75 in combination with everolimus in patients with CD70-positive metastatic renal cell carcinoma. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Diagnosis of metastatic renal cell carcinoma with confirmed CD70 expression - Previously treated with 1 or 2 tyrosine kinase inhibitors (TKIs) - Measurable disease - Eastern Cooperative Oncology Group performance status 0 or 1 - Adequate lung and renal function Other eligibility criteria may apply. - Prior treatment with anti-CD70-directed therapy - Prior treatment with an mTOR inhibitor Other exclusion criteria may apply. a31cf25cb5699c73b150c6db25a31696 9179 A Study to Assess the Safety, Pharmacokinetics and Effectiveness of AGS-16C3F Monotherapy in Subjects With Renal Cell Carcinoma (RCC) of Clear Cell or Papillary Histology I John Thompson, MD 20121076 41; 74 Kidney Cancer; Renal Cancer Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9179.html http://www.clinicaltrials.gov/ct/search?term=NCT01672775 NCT01672775 The purpose of this study is to evaluate the safety and pharmacokinetics and assess the immunogenicity and effectiveness of AGS-16C3F in subjects with renal cell cancer (RCC). Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Dose escalation cohorts: Histologically confirmed diagnosis of metastatic RCC of either clear cell or non-clear histology. - Tumors with clear cell histology: subject must have progressed after at least one anti-vascular endothelial growth factor receptor (anti-VEGFR) therapy - Tumors with non-clear cell histology must be ectonucleotide pyrophosphatase/phosphodiesterase family member 3 (ENPP3) positive at pre-screening. This sub-group does not have any prior therapy requirement. - Dose expansion cohorts: Histologically confirmed diagnosis of metastatic RCC of either clear cell or papillary histology - Tumors with clear cell histology: subject must have progressed after at least one anti-VEGFR therapy - Tumors with papillary histology: includes unclassified histology with papillary features and must be ENPP3 positive at pre-screening. This sub-group does not have any prior therapy requirement. - Measurable disease according to Response Criteria for Solid Tumors (RECIST Version 1.1) - Eastern Cooperative Group (ECOG) performance status of 0-1 - Hematologic function, as follows: - a) Absolute neutrophil count (ANC) = 1.5 x 109/L - b) Platelet count = 100 x 109/L - c) Hemoglobin = 9 g/dL (transfusions are allowed) - Renal function, as follows: - a) creatinine = 1.5 x upper limit of normal (ULN), or calculated glomerular filtration rate (GFR) > 50 mL/min if creatinine > 1.5x ULN - Hepatic function, as follows: - a) Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) = 2.5 x ULN or = 5x ULN if known liver metastases - b) Total bilirubin =1.5 x ULN - International normalized ratio (INR) < 1.3 (or = 3.0 if on therapeutic anticoagulation) - Women and men of childbearing potential must be advised and agree to practice effective methods of contraception during the course of the study and for 4 weeks after the last AGS-16C3F infusion administration Other eligibility criteria may apply. - Current uncontrolled central nervous system (CNS) metastasis or malignant brain tumors - Use of any investigational drug (including marketed drugs not approved for this indication) within 4 weeks prior to screening. No time limit applies to the use of marketed drugs approved for this indication provided that the subject has progressed on the treatment and all toxicities attributable to the drug have resolved or returned to baseline - Known sensitivity to any of the ingredients of the investigational product AGS-16C3F - History of thromboembolic events and bleeding disorders =3 months (e.g., (deep vein thrombosis) DVT or pulmonary embolism (PE)) - Active angina or Class III or IV Congestive Heart Failure (CHF) (New York Heart Association CHF Functional Classification System) or clinically significant cardiac disease within 12 months of study enrollment, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, congestive heart failure, uncontrolled hypertension, or arrhythmias not controlled by outpatient medication. - Major surgery within 4 weeks of study enrollment - Women who are pregnant (confirmed by positive pregnancy test) or lactating - Known positive test for human immunodeficiency virus (HIV), hepatitis C, or hepatitis B surface antigen. - Active infection requiring treatment with systemic (intravenous or oral) anti-infectives (antibiotic, antifungal, or antiviral agent) within 72 hours of screening. Other exclusion criteria may apply. b94191cde13240281acb6ac53d388733 9212 A Study of Pertuzumab in Combination With Herceptin (Trastuzumab) And Vinorelbine in First Line in Patients With Metastatic or Locally Advanced HER2-Positive Breast Cancer II Jennifer Specht, MD 20121111 13; 83 Breast Cancer; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9212.html http://www.clinicaltrials.gov/ct/search?term=NCT01565083 NCT01565083 This two-cohort, open-label, multicenter, phase II study will assess the safety and efficacy of pertuzumab given in combination with Herceptin (trastuzumab) and vinorelbine in first line in patients with metastatic or locally advanced HER2-positive breast cancer. Patients will receive pertuzumab 840 mg and Herceptin 8 mg/kg administered sequentially as separate iv infusions on Day 1 of Cycle 1. From Cycle 2 onwards, patients will receive pertuzumab 420 mg and Herceptin 6 mg/kg, administered either sequentially as separate iv infusions (Cohort 1) or together in one infusion bag (Cohort 2) every 3 weeks. Vinorelbine will be administered at 25 mg/m2 iv on Days 1 and 8 of Cycle 1, and at 30-35 mg/m2 on Days 1 and 8 of each following 3-week cycle. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs, or withdrawal of consent or death. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Adult patients, >/= 18 years of age - Histologically or cytologically confirmed adenocarcinoma of the breast with metastatic or locally advanced disease not amenable to curative resection - HER2-positive as assessed by local laboratory on primary or metastatic tumor - At least one measurable lesion and/or non-measurable disease evaluable according to RECIST version 1.1 criteria - Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 - Left ventricular ejection fraction (LVEF) of at least 55% - Life expectancy of at least 12 weeks Other eligibility criteria may apply. - Previous systemic non-hormonal anticancer therapy in the metastatic or locally advanced setting - Previous approved or investigative anti-HER2 agents in any breast cancer treatment setting, except trastuzumab and/or lapatinib in the adjuvant or neoadjuvant setting - Disease progression while receiving trastuzumab and/or lapatinib in the adjuvant or neoadjuvant setting - Disease-free interval from completion of adjuvant or neoadjuvant systemic non-hormonal treatment to recurrent disease of less than 6 months - History of persistent Grade 2 or higher (NCI-CTC Version 4.0) hematological toxicity resulting from previous adjuvant or neoadjuvant therapy - Radiographic evidence of central nervous system (CNS) metastases - Current peripheral neuropathy of Grade 3 or greater - History of other malignancy within the last 5 years, except for carcinoma in situ of the cervix or basal cell carcinoma - Serious uncontrolled concomitant disease that would contraindicate the use of any of the investigational drugs used in this study or would put the patients at high risk for treatment -related complications - Inadequate hematologic, liver or renal function - Uncontrolled hypertension or clinically significant cardiovascular disease - Hepatitis B, hepatitis C or HIV infection - Current chronic daily treatment with corticosteroids (>/= 10 mg/day methylprednisolone or equivalent), excluding inhaled steroids Other exclusion criteria may apply. b494d387bfcb97400afddbf5bde01d4b 9359 Sarcoma Study of MORAb-004 Utilization: Research and Clinical Evaluation. (SOURCE) II Robin Jones 20121175 83 Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9359.html http://www.clinicaltrials.gov/ct/search?term=NCT01574716 NCT01574716 This study is being done to see if MORAb-004 increases the effectiveness of the chemotherapies gemcitabine and docetaxel in people with metastatic Soft Tissue Sarcoma. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Be at least 18 years of age - Be surgically sterile or consent to use a medically acceptable method of contraception throughout the study period - Have a histologically confirmed diagnosis of mSTS as defined by the 4 specified study subgrouped - Have been treated in the metastatic setting with 0 to 2 prior systemic regimens for mSTS (Systemic treatment regimens given in the neoadjuvant setting and maintenance therapies will not be considered as regimens in the metastatic setting for the purposes of this protocol. Prior anthracycline-based regimen is allowable but not required. Subjects with extra-skeletal small round blue cell sarcomas, including rhabdomyosarcomas, must have exhausted or be intolerant of standard first line anthracycline-based chemotherapy.) - Have measurable disease, as defined by RECIST v 1.1 assess within 2 weeks of study entry and have radiologically documented disease progression greater than or equal to a 10% increase in the sum of the longest diameters of target lesions present within 6 months prior to randomization - Have tumor tissue available for TEM-1 biomarker studies - Be willing and able to provide written informed consent Other eligibility criteria may apply. - Have received more than 2 prior systemic treatment regimens for mSTS - Have received either gemcitabine or docetaxel in any previous treatment for mSTS (regardless of the line of treatment) - Have a diagnosis of primary bone sarcoma of any histological type. - Have a history of clinically significant heart disease, or clinically significant arrhythmia on ECG within the past 6 months - Have a history of allergic reaction to prior monoclonal antibody or biologic agent - Have received previous treatment with MORAb-004 (anti-TEM-1) - Have a medical condition with a high risk of bleeding (e.g., a known bleeding disorder, a coagulopathy, or a tumor that involves the major vessels) or have a recent (within past 6 months) history of a significant bleeding event - Have undergone major surgical procedures or open biopsy, have significant traumatic injury within 30 days prior to the first date of study treatment, or have major surgical procedures anticipated during the study - Have a serious non-healing wound, an ulcer (including gastrointestinal), or a bone fracture Other exclusion criteria may apply. 4fbdad87accb335a1859f17456e9cef1 9504 Study of MK-3475 Versus Chemotherapy in Participants With Advanced Melanoma (P08719/MK-3475-002) II Kim Margolin, MD 20121298 52; 83 Melanoma; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9504.html http://www.clinicaltrials.gov/ct/search?term=NCT01704287 NCT01704287 This study is being done to compare survival using MK-3475 or standard chemotherapy for participants with advanced melanoma (MEL) who have progressed after prior therapy. Participants will be randomized to receive either low dose MK-3475, higher dose MK-3475, or Investigator-choice chemotherapy. The MK-3475 dose will be blinded to Investigators and participants. The randomization to either MK-3475 or Investigator choice chemotherapy will be conducted in open-label fashion. The five standard chemotherapy choices are carboplatin + paclitaxel, carboplatin alone, paclitaxel alone, dacarbazine, or temozolomide. Ages Eligible for Study: 16 Years and older Genders Eligible for Study: Both - Histologically or cytologically confirmed diagnosis of unresectable Stage III or metastatic MEL not amenable to local therapy - Participants must have progressive disease after the most recent treatment regimen - Must consent to allow correlative studies and should have available tumor tissue - Radiographically measurable disease - Eastern Cooperative Oncology Group Performance Status of 0 or 1 Other eligibility criteria may apply. - Chemotherapy, radiation therapy, or biological therapy within four weeks prior to the first dose of study drug, or not recovered from the AEs due to cancer therapies administered more than four weeks earlier - Participating or has participated in a study of an investigational agent or using an investigational device within 30 days of the first dose of study drug - Expected to require any other form of systemic or localized antineoplastic therapy while on study - Chronic systemic steroid therapy within two weeks before the planned date for first dose randomized treatment or on any other form of immunosuppressive medication - Known history of any other than the current malignancy excepting adequately treated basal or squamous cell carcinoma of the skin, superficial bladder cancer, in situ cervical cancer, breast cancer, or other in situ cancers - Known active central nervous system (CNS) metastases and/or carcinomatous meningitis - Active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents - Prior treatment with any other anti-programmed cell death (PD) agent - Active infection requiring systemic therapy - Known history of Human Immunodeficiency Virus (HIV) - Active Hepatitis B or Hepatitis C - Regular user (including recreational use of) illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol) - Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study. Other exclusion criteria may apply. 27ce6f53a71342bb02225af93ee56ea2 9339 Study of BMS-936558 Compared to Docetaxel in Previously Treated Advanced or Metastatic Squamous Cell Non-small Cell Lung Cancer (NSCLC) III Laura Chow 20121428 46 Lung Cancer Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9339.html http://www.clinicaltrials.gov/ct/search?term=NCT01642004 NCT01642004 The purpose of the study is to compare the change in tumor size, and overall survival of BMS-936558 as compared with Docetaxel in subjects with squamous cell non-small cell lung cancer (NSCLC), after failure of prior platinum-based chemotherapy. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Men & women =/> 18 years of age - Subjects with histologically or cytologically-documented squamous cell NSCLC who present with Stage IIIB/IV disease or recurrent disease following radiation therapy or surgical resection - -Disease recurrence or progression during/after one prior platinum-containing chemotherapy regimen for advanced or metastatic disease - Measurable disease by Computed tomography (CT)/Magnetic resonance imaging (MRI) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria - Eastern Cooperative Oncology Group (ECOG) performance status =/< 1 - An formalin fixed, paraffin-embedded (FFPE) tumor tissue block or unstained slides of tumor sample (archival or recent) must be available for biomarker evaluation. Specimens must be received by the central lab prior to randomization. Biopsy should be excisional, incisional or core needle. Fine needle aspiration is insufficient Other eligibility criteria may apply. - Subjects with active Central nervous system (CNS) metastases are excluded. Subjects are eligible if CNS metastases are adequately treated and subjects are neurologically returned to baseline for at least 2 weeks prior to enrollment. In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of =/< 10mg daily prednisone (or equivalent) - Subjects with carcinomatous meningitis - Subjects with active, known or suspected autoimmune disease, or subjects with interstitial lung disease - Subjects with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of randomization - Prior therapy with anti-Programmed death-1 (PD-1), anti-Programmed cell death ligand 1 (PD-L1), anti-Programmed cell death ligand 2 (PD-L2), anti-CD137, or anti-Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) - Prior treatment on the first line study CA184104 first line NSCLC study - Prior treatment with docetaxel - Treatment with any investigational agent within 28 days of first administration of study treatment Other exclusion criteria may apply. 5b3b9dbe86a720db440c10f4a5264ac7 8562 A Study of Alpharadin® With Docetaxel in Patients With Bone Metastasis From Castration-Resistant Prostate Cancer (CRPC) I/II Tia Higano, MD 20121484 71; 83 Prostate Cancer; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8562.html http://www.clinicaltrials.gov/ct/search?term=NCT01106352 NCT01106352 The main purpose of this study is to establish a recommended dose of Alpharadin® to be used in combination with docetaxel in patients with bone metastases from castration-resistant prostate cancer and to investigate safety and explore efficacy of the recommended dose. es Eligible for Study: 18 Years and older Genders Eligible for Study: Male - Histologically or cytologically confirmed adenocarcinoma of the prostate. - Two or more bone metastases (hot spots) confirmed by bone scintigraphy within 8 weeks prior to study entry - Known castration-resistant disease - Karnofsky Performance Status (KPS): =/> 70% within 14 days before start of study treatment (ECOG 1) - Life expectancy at least 6 months. - Acceptable hematology and serum biochemistry screening values - Eligible for use of docetaxel according to the product information (package insert or similar). Other eligibility criteria may apply. - Has received an investigational therapeutic drug within the last 4 weeks prior to start of study treatment, or is scheduled to receive one during the treatment period. - Has received external radiotherapy within the last 4 weeks prior to start of study treatment. - Has an immediate need for radiotherapy. - Has received prior hemibody external radiotherapy . - Has received systemic radiotherapy (e.g. samarium, strontium etc.) for the treatment of bone metastases. - Has received cytotoxic chemotherapy within the last 4 weeks prior to start of study treatment, or has not recovered to grade 1 or 0 from adverse events due to cytotoxic chemotherapy administered more than 4 weeks earlier. - Has received more than ten previous infusions of docetaxel. - Previous known experience of grade =/> 3 docetaxel related toxicities or docetaxel toxicity related dose interruption or discontinuation. - Previous use of G-CSF for persistent neutropenia after docetaxel treatment. - Has received blood transfusion or erythropoietin (EPO) within the last 4 weeks prior to start of study treatment. - Has received prior treatment with Alpharadin. - Malignant lymphadenopathy exceeding 3 cm in short-axis diameter. - Symptomatic nodal disease, i.e. scrotal, penile or leg edema. - Visceral metastases from CRPC (>2 lung and/or liver metastases [size =/>2cm]), as assessed by CT scan of the chest/abdomen/pelvis within the last 8 weeks prior to start of study treatment. - Uncontrolled loco-regional disease. - Other primary tumor (other than CRPC) including haematological malignancy present within the last 5 years (except non-melanoma skin cancer or low-grade superficial bladder cancer). - Has imminent or established spinal cord compression based on clinical findings and/or MRI. - Unmanageable fecal incontinence. Other exclusion criteria may apply. 3ebbab327ea9724a5122072e05ef6ef4 9381 Study of BMS-936558 Compared to Docetaxel in Previously Treated Advanced or Metastatic Non-squamous NSCLC III Laura Chow 20121498 46; 83 Lung Cancer; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9381.html http://www.clinicaltrials.gov/ct/search?term=NCT01673867 NCT01673867 The purpose of the study is to compare the overall survival of BMS-936558 as compared with Docetaxel in subjects with non-squamous cell non-small cell lung cancer (NSCLC) after failure of prior platinum-based chemotherapy Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Men & women = to or > 18 years of age - Subjects with histologically or cytologically-documented locally advanced non-squamous cell NSCLC who present with Stage IIIB/IV disease or recurrent disease following radiation therapy or surgical resection - Disease recurrence or progression during/after one prior platinum-containing doublet chemotherapy regimen for advanced or metastatic disease - Measurable disease by Computed tomography (CT)/Magnetic resonance imaging (MRI) per RECIST 1.1 criteria - Eastern Cooperative Oncology Group (ECOG) performance status = to or < 1 - A formalin fixed, paraffin-embedded (FFPE) tumor tissue block or unstained slides of tumor sample (archival or recent) must be available for biomarker evaluation. Specimens must be received by the central lab prior to randomization. Biopsy should be excisional, incisional or core needle. Fine needle aspiration is insufficient Other eligibility criteria may apply. - Subjects with active Central nervous system (CNS) metastases are excluded. Subjects are eligible if CNS metastases are adequately treated and subjects are neurologically returned to baseline for at least 2 weeks prior to enrollment. In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of = to or < 10mg daily Prednisone (or equivalent) - Subjects with carcinomatous meningitis. - Subjects with active, known or suspected autoimmune disease, or subjects with interstitial lung disease - Subjects with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of randomization - Prior therapy with anti-programmed death-1 (anti-PD-1), anti programmed cell death ligand 1 (anti-PD-L1), anti programmed cell death ligand 2 (anti-PD-L2), anti-CD137, or anti Cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4) antibody (including Ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) Other exclusion criteria may apply. c2f485feb47644a426f43007e4d87a1e 9382 A Trial of Dalotuzumab in Combination With Irinotecan Versus Cetuximab and Irinotecan for Participants With Metastatic Rectal Cancers (mRC) (MK-0646-025 AM3) II William Ellis 20121505 73; 83 Rectal Cancer; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9382.html http://www.clinicaltrials.gov/ct/search?term=NCT01667536 NCT01667536 The purpose of this adaptive trial is to compare the progression-free survival of participants with metastatic rectal carcinoma when treated with dalotuzumab + irinotecan therapy relative to participants treated with cetuximab + irinotecan. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Metastatic colorectal cancer with primary tumor originating from the rectum - Available archival (recent or remote) tumor, or newly obtained formalin-fixed tissue available for analysis for biomarker studies - At least one measurable lesion greater than or equal to 10 mm - Disease has progressed after treatment with both irinotecan and oxaliplatin containing regimens and should have progressed on or within 3 months of completing their last line of therapy - Performance status 0-1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale Other eligibility criteria may apply. - Known diabetic who is poorly controlled - Chemotherapy or biological therapy within 2 weeks prior to initial dosing on this study, or whose toxicities from agents administered 2 weeks earlier have not resolved to at least grade 1 or baseline, or who is within 3 weeks from a prior surgery - Radiotherapy within 2 weeks prior to initial dosing on this study, unless the radiotherapy was for management of pain - Currently participating or has participated in a study with an investigational compound or device within 30 days or 5 half-lives of the investigational agent, whichever is longer, of initial dosing on this study - Could not complete previous course of irinotecan due to intolerable toxicity, other than discontinuation due to fatigue following prolonged administration (>4 months exposure) - Prior exposure to insulin-like growth factor 1 receptor (IGF-1R) inhibitors or epidermal growth factor receptor (EGFR) inhibitors - Known Central Nervous System (CNS) metastases and/or carcinomatous meningitis - Primary CNS tumor - History of a prior malignancy with the exception of cervical intraepithelial neoplasia; basal cell carcinoma of the skin; adequately treated localized prostate carcinoma; potentially curative therapy with no evidence of that disease for 5 years, deemed low risk for recurrence by treating physician. - Human Immunodeficiency Virus (HIV)-positive - Active Hepatitis B or C receiving antiviral treatment regimens - Symptomatic ascites or pleural effusion - Concurrently using growth hormone (GH), or growth hormone inhibitors Other exclusion criteria may apply. c6992f3a7c8c7c51f4e9544e1e0bc5b1 9408 A Study of AT13387 in Patients With Non-Small Cell Lung Cancer (NSCLC) Alone and in Combination With Crizotinib I/II Renato Martins, MD, MPH 20121654 46; 83 Lung Cancer; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9408.html http://www.clinicaltrials.gov/ct/search?term=NCT01712217 NCT01712217 The purpose of the study is to evaluate safety and efficacy of AT13387 Alone and in Combination with Crizotinib in the Treatment of Non-small Cell Lung Cancer. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - 1) Men or women 18 years of age or older - 2) Must have Non-small Cell Lung Cancer with ALK+ mutation or other mutations or rearrangements potentially sensitive to crizotinib - 3) Measurable disease - 4) Must have been receiving or have received crizotinib - 5) Have adequate cardiac, bone marrow, liver and kidney function - 6) Must be willing and able to provide written informed consent and comply with the protocol and study procedures Other eligibility criteria may apply. - 1) Prior anti-cancer treatment with any HSP90 inhibitor - 2) Have received chemotherapy, radiation therapy or other anticancer treatment other than crizotinib within 3 weeks prior to the first dose of study drug - 3) Prior malignancy other than adequately treated basal or squamous cell carcinoma of the skin, superficial bladder cancer, low-grade cervical cancer, non-metastatic prostate cancer, or have been disease-free for at least 3 years - 4) Abnormal heart function - 5) Presence of a life-threatening illness, medical condition, organ system dysfunction, or other factors - 6) Hypersensitivity of AT13387 or other components of the drug product - 7) Treatment with an investigational drug within 3 weeks prior to the first dose of study drug - 8) Severe systemic diseases or active uncontrolled infections - 9) Known history of human immunodeficiency virus (HIV) or seropositive test for hepatitis C virus or hepatitis B virus Other exclusion criteria may apply. 380dfbef0c4e98ca740a8ac05bed9b8a 9455 Study of BMS-936558 vs. Everolimus in Pre-Treated Advanced Or Metastatic Clear-cell RCC III Scott Tykodi, MD 20121671 41; 74; 83 Kidney Cancer; Renal Cancer; Solid Tumors Dan Leatham 206/288-7370 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9455.html http://www.clinicaltrials.gov/ct/search?term=NCT01668784 NCT01668784 The purpose of the study is to compare the clinical benefit, as measured by duration of overall survival, of BMS-936558 vs. Everolimus in subjects with advanced or metastatic clear-cell renal cell carcinoma who have received prior anti-angiogenic therapy Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Men & women =/> 18 years of age - Histologic confirmation of Renal cell carcinoma (RCC) with clear-cell component - Advanced/metastatic RCC - Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria - Received 1 or 2 prior anti-angiogenic therapy regimens in advanced or metastatic setting - No more than 3 total prior systemic treatment regimens in the advanced or metastatic setting, and evidence of progression on or after last treatment regimen received and within 6 months of enrollment - Karnofsky Performance Score =/> 70% Other eligibility criteria may apply. - Any Central Nervous System (CNS) metastases or history of CNS metastases - Prior therapy with an Mammalian target of rapamycin (mTOR) inhibitor - Any active known or suspected autoimmune disease. - Uncontrolled adrenal insufficiency - Active chronic liver disease - Prior malignancy active within past 3 years, except for locally curable cancers Other exclusion criteria may apply. 079a2595069b15c2b9792086930dba3e 9393 Phase 1 Biomarker Study of Anti-PD-1 in Advanced Melanoma I Shailender Bhatia, MD 20122036 52; 83 Melanoma; Solid Tumors Dan Leatham 206/288-7370 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9393.html http://www.clinicaltrials.gov/ct/search?term=NCT01621490 NCT01621490 The purpose of this study is to evaluate pharmacodynamic changes of BMS-936558 treatment on the biomarkers measured in the peripheral blood and tumor tissues of subjects with advanced melanoma (unresectable or advanced). Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Men and women > 18 years - Eastern Cooperative Oncology Group (ECOG) status = 0 to 1 - Subjects with unresectable Stage III or IV melanoma who are either refractory or intolerant to, or have refused standard therapy for treatment of metastatic melanoma - Subject must have histologic or cytologic confirmation of advanced melanoma - Subjects must have at least one measurable lesion at baseline by computed tomography (CT) or magnetic resonance imaging (MRI) as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria - Subjects must have at least 1 tumor site that can be biopsied at acceptable clinical risk and must consent to pre- and post-treatment biopsies Other eligibility criteria may apply. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Men and women > 18 years - Eastern Cooperative Oncology Group (ECOG) status = 0 to 1 - Subjects with unresectable Stage III or IV melanoma who are either refractory or intolerant to, or have refused standard therapy for treatment of metastatic melanoma - Subject must have histologic or cytologic confirmation of advanced melanoma - Subjects must have at least one measurable lesion at baseline by computed tomography (CT) or magnetic resonance imaging (MRI) as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria - Subjects must have at least 1 tumor site that can be biopsied at acceptable clinical risk and must consent to pre- and post-treatment biopsies Other exclusion criteria may apply. 403f8aa02a0b22883f7db6701740576f 9421 Study of the Effect of GTx-758 on Serum PSA and Testosterone in Men With Prostate Cancer II Evan Yu, MD 20122140 30; 71; 83 Genitourinary Cancer; Prostate Cancer; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9421.html http://www.clinicaltrials.gov/ct/search?term=NCT01615120 NCT01615120 Protocol G200712 is a Phase II, exploratory study to assess the effects of GTx-758 on serum prostate specific antigen (PSA) response ans serum PSA progression in men with Metastatic Castration Resistant Prostate Cancer (mCRPC) on Androgen Deprivation Therapy (ADT) with luteinizing hormone-releasing hormone (LHRH) agonists, LHRH antagonists, or orchidectomy. This study will also assess the venous thromboembolism (VTE) risk of lower doses of GTx-758. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Male - Be over age 18 years - Be able to Communicate effectively with the study personnel - Have histologically confirmed prostate cancer - Have castration resistant prostate cancer patients with radiographic evidence of metastatic disease (T any - N any - MI) - ECOG performance status of 0 to 2 - Have been treated with ADT (chemical or surgical) for at least 6 months - Have a castrate level of serum total testosterone (< 50ng/dL) - Have a history of serum PSA response on ADT. A serum PSA response is an undetectable level of serum PSA (=/< 0.2/mL) or at least a 90% reduction in serum PSA from the serum PSA value prior to the initiation of treatment to < 10ng/mL - Have a rising serum PSA on two successive assessments at least 2 weeks apart and serum PSA levels =/> 2ng/mL or > 2 ng/mL and a 25% increase above the nadir from the ADT. - Be continued on ADT throughout this study - give written informed consent prior to any study specific procedures - subjects must agree, if not already on anticoagulation therapy or aspirin, to take 81 mg aspirin daily throughout the duration of their participation in this study and for 30 days after completion of dosing with GTx-758. - Subjects must agree to use acceptable methods of contraception: - If their female partners are pregnant or lactating, acceptable methods of contraception from the time of the first administration of study medication until 3 months following administration of the last dose of study medication must be used. Acceptable methods are: condom used with spermicidal foam/gel/film/cream/suppository. If the subject has undergone surgical sterilization (vasectomy with documentation of azospermia), a condom with spermicidal foam/gel/film/cream/suppository should be used. - If the male subject's partner could become pregnant, use acceptable methods of contraception from the time of the first administration of study medication until 3 months following administration of the last dose of study medication.Acceptable methods of contraception are as follows: condom with spermicidal foam/gel/film/cream/suppository [i.e., barrier method of contraception], surgical sterilization (vasectomy with documentation of azospermia) and a barrier method {condom used with spermicidal foam/gel/fil/cream/suppository}, the female partner uses oral contraceptives (combination estrogen/progesterone pills), injectible progesterone or subdermal implants and a barrier method {condom used with spermicidal foam/gel/film/cream/suppository}. - If the female partner has undergone documented tubal ligation (female sterilization), a barrier method {condom used with spermicidal foam/gel/film/cream/suppository} should be used - If the female partner has undergone documented placement of an intrauterine device (IUD) or intrauterine system (IUS), a barrier method {condom with spermicidal foam/gel/film/cream/suppository} should also be used. Other eligibility criteria may apply. - Known hypersensitivity or allergy to estrogen or estrogen like drugs - Need for urgent chemotherapy, radiation therapy or surgical intervention for prostate cancer in the opinion of the investigator - Any disease or condition (medical or surgical) which might compromise the hematologic, cardiovascular, endocrine, pulmonary, renal, gastrointestinal, hepatic, or central nervous system; or other conditions that may interfere with the absorption, distribution, metabolism or excretion of study drug, or would place the subject at increased risk - Subjects with a personal history of abnormal blood clotting or thrombotic disease (venous or arterial thrombotic events such as history of stroke, deep vein thrombosis (DVT), and or pulmonary embolus (PE)). - Any subjects, as determined by a central laboratory, with --- 1) a modified activated protein C reaction ratio =/< 2.5 and a Factor V Leiden gene mutation, --- 2) an antithrombin level below the lower limit of the normal range, --- 3) a serum homocystine level exceeding the upper limit of the normal range --- 4) an antiphospholipid antibody level that is indeterminate, positive, or outside the normal range, --- 5) or a prothrombin gene mutation - Symptomatic congestive heart failure (NYHA Class III - IV), unstable angina pectoris, cardiac arrhythmia, or history of atrial fibrillation - The presence of consistently abnormal laboratory values which are considered clinically significant. In addition, any subject with liver enzymes (ALT or AST) above 2 times the upper limit of normal, total bilirubin above 2 times the upper limit of normal, or serum creatinine above 1.5 times the upper limit of normal will NOT be admitted to the study. - Received an investigational drug within a period of 90 days prior to the enrollment in the study. - Received the study medication GTx-758 previously; - Currently taking testosterone, testosterone like agents, 5a-reductase inhibitor (finasteride, dutasteride),or antiandrogens (bicalutamide, flutamide or nilutamide). Subjects taking a 5a-reductase inhibitor or one of these antiandrogens may be eligible if the subject undergoes a 6 week washout period after stopping therapy. The subject must have at least two rising serum PSA levels at least 2 weeks apart after therapy with these 5a-reductase inhibitor or these antiandrogens have been stopped (antiandrogen withdrawal)and complete the 6-week washout period to be eligible; - Have previously taken or are currently taking diethylstilbestrol, other estrogens, abiraterone or ketoconazole or any other inhibitor of CYP17 (17a-hydroxylase/C17,20-lyase); - Currently having radiation therapy to prostate for cancer control (radiation to bone to relieve pain is acceptable) - Have previously taken or are currently taking enzalutamide; - Have previously received cytotoxic chemotherapy for prostate cancer; - Recent hospitalization (within 30 days of screening); - Recent surgery (within 30 days of screening); - Have taken body building or fertility supplements within 4 weeks of admission into the study; - Have been previously diagnosed or treated for active cancer (other than prostate cancer or non-melanoma skin cancer)within the previous five years; - Have a BMI > 35. Other exclusion criteria may apply. 488c44e6242a8086cd5d316f8ee4407d 8128 A Study to Investigate the Efficacy and Safety of Bendamustine Compared With Bendamustine+RO5072759 (GA101) in Patients With Rituximab-Refractory, Indolent Non-Hodgkin's Lymphoma (GADOLIN) III Oliver Press, MD, PhD 2388.00 36; 48; 64 Hematologic Malignancies; Lymphoma; Non-Hodgkin's Lymphoma (NHL) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8128.html http://www.clinicaltrials.gov/ct/search?term=NCT01059630 NCT01059630 This is an open-label, multicenter, randomized, Phase III study to investigate the efficacy and safety of GA101 combined with bendamustine compared with bendamustine alone in patients with rituximab-refractory, indolent Non-Hodgkin's lymphoma (NHL). Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - History of histologically documented, CD20+, indolent NHL - Refractory to any previous regimen containing rituximab - Previously treated with a maximum of three unique chemotherapy containing treatment regimens - All patients must have at least one bi-dimensionally measurable lesion (>1.5 cm in its largest dimension by CT scan) Other eligibility criteria may apply. - Prior use of any monoclonal antibody (other than anti-CD20) within 3 months - Chemotherapy or other investigational therapy within 28 days - Prior treatment with bendamustine within 1 year - Prior allogeneic stem cell transplant - History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (e.g., patients in whom re-dosing with rituximab would be contraindicated for safety reasons) - History of sensitivity to mannitol - Central nervous system lymphoma or histological evidence of transformation to high grade or diffuse large B-cell lymphoma - History of other malignancy that could affect compliance with the protocol or interpretation of results - Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results - Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) or any major episode of infection requiring treatment with intravenous antibiotics or hospitalization within 4 weeks - Vaccination with a live vaccine a minimum of 28 days prior to randomization - Recent major surgery (within 4 weeks), other than for diagnosis - Presence of positive test results for Hepatitis B or Hepatitis C - Known history of HIV seropositive status - Positive test results for human T-lymphotropic virus type I (HTLV 1) virus in endemic countries - Women who are pregnant or lactating - Agreement to use an effective form of contraception for the duration of the study - Ongoing corticosteroid use >30 mg/day prednisone or equivalent Other exclusion criteria may apply. d19719fa4313321d06b2d579a4b48e9f 8215 A Phase 1/2 Study of ARRY-520 in Patients With Relapsed or Refractory Multiple Myeloma I/II Bill Bensinger, MD 2402.00 36; 57 Hematologic Malignancies; Multiple Myeloma (MM) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8215.html http://www.clinicaltrials.gov/ct/search?term=NCT00821249 NCT00821249 Purpose ARRY-520 is designed to prevent cancer cells from reproducing. By preventing the tumor cells from reproducing, ARRY-520 may slow the spread of the cancer cells and may cause them to die. ARRAY-520-212 is a study meant for patients with relapsed or refractory multiple myeloma or plasma cell leukemia, who have already received at least two previous treatments. Prior treatments should include bortezomib and an immunomodulatory agent, such as thalidomide and/or lenalidomide, unless the patients were not eligible or refused to receive those treatments. In the first part of this study, patients will receive increasing doses of a novel kinesin spindle protein inhibitor (KSP inhibitor) in order to achieve the highest dose possible that will not cause unacceptable side effects. In the second part of the study, a larger group of patients will receive the best dose determined from the first part of the study. Both groups of patients will be followed to see what side effects ARRY-520 causes and to see what effectiveness it has, if any in treating the cancer. - Confirmed relapsed or refractory MM or PCL. Patients should have received at least two prior treatment regimens. Prior treatment must have included bortezomib and an immunomodulatory agent (e.g., thalidomide and/or lenalidomide), unless patients were not eligible or refused to receive these treatments. The disease should have progressed during or after the last prior treatment regimen. - Measurable MM disease, defined as one of the following: A monoclonal immunoglobulin (Ig) concentration on serum electrophoresis of = 1.0 g/dL for an IgG myeloma, 0.5 g/dL for an IgA myeloma, and 0.1 g/dL for an IgD myeloma; Measurable urinary light chain secretion by quantitative analysis of = 200 mg/24 hours; Involved serum free light chain (FLC) level = 10 mg/dL, provided the serum FLC ratio is abnormal; Patients with oligo- or non-secretory disease must have bone marrow involvement with at least 30% plasmacytosis on aspiration. - Male or female, = 18 years of age at time of signing consent. - Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1. - Adequate hematology laboratory values without transfusion support within two weeks of screening: Hemoglobin = 8 g/dL; Absolute neutrophil count (ANC) = 1.5 x 109/L; Platelets = 75 x 109/L. - Adequate liver and renal function: Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and/or alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) = 2.5 x the upper limit of normal (ULN); Bilirubin < 1.5 mg/dL; Serum creatinine = 2.5 mg/dL, and a calculated creatinine clearance of at least 50 mL/min (using the Cockcroft and Gault method). - If patient is female and of childbearing potential, she must have a negative serum beta human chorionic gonadotropin (ß HCG) test. - Male patients and female patients of childbearing potential must agree to use an effective method of contraception per institutional standard. - Signed informed consent prior to initiation of any study-related procedures that are not considered standard of care. Other eligibility criteria may apply. - Primary amyloidosis. - Concomitant malignancies or previous malignancies with less than a three-year disease free interval at the time of enrollment. Patients with adequately resected basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or Stage A low grade prostate cancer may enroll irrespective of the time of diagnosis. - Autologous or allogeneic stem cell or bone marrow transplant within 3 months prior to first dose of study drug. - Treatment with an investigational product or device within 28 days of initiating study drug. - Cytotoxic therapy or monoclonal antibodies within 21 days prior to first dose of study drug. - Radiotherapy within 21 days prior to first dose of study drug. However, if the radiation portal covered = 5% of the bone marrow reserve, the patient may be enrolled irrespective of the end date of radiotherapy. - Major surgery within two weeks prior to first dose of study drug. - Corticosteroid doses > 10 mg/day within two weeks prior to first dose of study drug. - Any serious medical or psychiatric disorder that would interfere with patient safety or informed consent. - Any severe concurrent disease or condition (including active systemic infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia), which, in the judgment of the Investigator, would make the patient inappropriate for study participation. - Known positive serology for the Human Immunodeficiency Virus (HIV), Hepatitis B and/or active Hepatitis C. Other exclusion criteria may apply. 3e2b729a2d35169237a9cc756c99ba5c 8871 A Study of AC220 Given After Transplant in Subjects With Acute Myeloid Leukemia (AML) I Brenda Sandmaier, MD 2487.00 2; 36; 43 Acute Myeloid Leukemia (AML); Hematologic Malignancies; Leukemia Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8871.html http://www.clinicaltrials.gov/ct/search?term=NCT01468467 NCT01468467 The purpose of this study is to define a safe dose of AC220 when given as maintenance therapy after treatment with an allogeneic stem cell transplant. - Ages Eligible for Study: 18 Years and older - Genders Eligible for Study: Both - Subject has a diagnosis of acute myeloid leukemia (AML) according to WHO classification (2008) and has received a high dose or a reduced intensity conditioning allogeneic Hematopoietic Stem Cell Transplant (HSCT) during first or second remission and within 30 to 60 days prior to first dose of AC220. Donors may be human leukocyte antigen (HLA)-matched for HLA-A, B, C, DRB1, and DQB1 by high resolution typing, related or unrelated (only a single allele disparity will be allowed for HLA-A, B, or C as defined by high resolution typing) - Subject has documentation that is positive for FLT3-ITD activating mutation from initial diagnosis - Subject must be in morphologic remission (< 5% marrow blasts) and without active central nervous system (CNS) AML within 14 days prior to first dose of AC220 - Subject must have CD3 donor chimerism > 50 % at Screening - Subject has a Karnofsky Performance Status (KPS) of = 60 - Subject must have absolute neutrophil count (ANC) > 1000/mm3 and platelet count > 50,000/mm3 without platelet transfusion support within 2 weeks prior to first dose - Subject must have adequate renal, hepatic, and coagulation parameters as indicated by the following laboratory values: - Alkaline phosphatase, aspartate aminotransferase (AST), alanine aminotransferase (ALT) = 2.5 x institutional upper limit of normal (ULN) - Total bilirubin = 1.5 x institutional ULN - Serum creatinine = 1.5 x institutional ULN or an estimated glomerular filtration rate (eGFR) of > 50 ml/min as calculated by the Modification of Diet in Renal Disease (MDRD) equation - If subject is a woman of childbearing potential (WOCBP) or a male subject with female partner of childbearing potential, the subject agrees to use a medically-approved method of contraception to avoid pregnancy throughout the study and for at least 3 months after the last dose of study drug - If subject is a WOCBP, subject has a negative serum or urine pregnancy test (sensitivity = 25 IU human chorionic gonadotropin [hCG]/L) within 72 hours prior to the start of study drug administration - Subject is able to comply with study procedures and follow-up examinations Other eligibility criteria may apply. - Subject received AC220 and relapsed during treatment with AC220 - Subject has active = Grade 2 graft versus host disease (GVHD) - Subject has received concurrent chemotherapy, immunotherapy, or radio-therapy within 21 days prior to the first dose of AC220, or any antineoplastic therapy that is considered to be investigational (i.e., used for non-approved indications(s) and in the context of a research investigation) within 30 days or 5 half-lives (whichever is longer) prior to the first dose of study drug - Subject requires treatment with concomitant drugs that prolong QT/QTc interval or strong cytochrome P-3A4 (CYP3A4) inhibitors or inducers with the exception of immunosuppressants, antibiotics, antifungals, and antivirals that are used as standard of care post-transplant or to prevent or treat infections and other such drugs that are considered absolutely essential for the care of the subject - Subject requires treatment with anticoagulant therapy - Subject has a known positive test for human immunodeficiency virus, hepatitis C, or hepatitis B surface antigen - Subject had major surgery within 4 weeks prior to first dose of AC220 - Subject has uncontrolled or significant cardiovascular disease - Subject has an active acute fungal, bacterial, or other infection that is unresponsive to therapy - Subject is a female who is lactating - Subject has any medical, psychiatric, addictive or other kind of disorder which compromises the ability of the subject to give written informed consent and/or to comply with procedures Other exclusion criteria may apply. 4a0c8e33eee0ffc15c2a8c86b5dac0b8 8586 A Study to Evaluate Pazopanib as an Adjuvant Treatment for Localized Renal Cell Carcinoma (RCC) (PROTECT) III Scott Tykodi, MD 2489.00 74; 83 Renal Cancer; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8586.html http://www.clinicaltrials.gov/ct/search?term=NCT01235962 NCT01235962 This randomized Phase III study is to evaluate whether pazopanib compared with placebo can prevent or delay recurrence of kidney cancer in patients with moderately high or high risk of developing recurrence after undergoing kidney cancer surgery Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both Signed written informed consent Diagnosis of RCC with clear-cell or predominant clear-cell histology Subjects with non-metastatic disease (M0) fulfilling any of the following combinations of pathologic staging based on American Joint Committee on Cancer (AJCC) TNM staging version 2010 and Fuhrman nuclear grading. - pT2, G3 or G4, N0; or, - pT3, G any, N0; or, - pT4, G any, N0; or, - pT any, G any, N1 Fulfill all of the following criteria of disease-free status at baseline: - Had complete gross surgical resection of all RCC via radical or partial nephrectomy using either open or laparoscopic technique. - Baseline imaging of chest, abdomen and pelvis shows no metastasis or residual tumor lesions as confirmed centrally by an independent radiologist. Received no prior adjuvant or neo-adjuvant treatment for RCC Recovered from nephrectomy: any surgery related toxicities should be reduced to = grade 1 per NCI Common Terminology Criteria for Adverse Events (CTCAE) (Version 4) Karnofsky performance scale (KPS) of = 80 Adequate organ system function Other eligibility criteria may apply. History of another malignancy. Exception: Subjects who have had another malignancy and have been disease-free for 5 years, or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to: - Active peptic ulcer disease - Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), or other gastrointestinal conditions with increased risk of perforation - History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment Active diarrhea of any grade Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to: - Malabsorption syndrome - Major resection of the stomach or small bowel History of human immunodeficiency virus (HIV) infection History of active hepatitis Presence of uncontrolled infection. History of any one or more of the following cardiovascular conditions within the past 6 months: - Cardiac angioplasty or stenting - Myocardial infarction - Unstable angina - Coronary artery bypass graft surgery - Symptomatic peripheral vascular disease History of Class III or IV congestive heart failure, as defined by the New York Heart Association Classification of Congestive Heart Failure History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. Corrected QT interval (QTc) > 480 milliseconds (msec) Poorly controlled hypertension, defined as systolic blood pressure (SBP) of =140 mmHg or diastolic blood pressure (DBP) of = 90mmHg. Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. Blood pressure (BP) must be re-assessed on two occasions that are separated by a minimum of 1 hour; on each of these occasions, the mean (of 3 readings) SBP / DBP values from each BP assessment must be <140/90 mmHg in order for a subject to be eligible for the study (see Section 7.6.2 for instruction on blood pressure measurement and obtaining mean blood pressure values). Evidence of active bleeding or bleeding diathesis Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures Unable or unwilling to discontinue use of prohibited medications for at least 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of study treatment and for the duration of the study. Concurrent therapy given to treat cancer including treatment with an investigational agent or concurrent participation in another clinical trial involving anti-cancer investigational drug. Administration of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study treatment. Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib or excipients that in the opinion of the investigator contraindicates their participation. Prior or current use of systemic anti-VEGF inhibitors, cytokines (e.g. interferon, interleukin 2). Other exclusion criteria may apply. 87ed4b482cb816e6a18240a744007804 8623 A Study to Evaluate the Safety of Long-term Treatment With Siltuximab in Patients With Multicentric Castleman's Disease II Corey Casper 2502.00 49 Lymphoproliferative Disease Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8623.html http://www.clinicaltrials.gov/ct/search?term=NCT01400503 NCT01400503 Purpose The purpose of this study is to assess the safety of extended treatment with siltuximab in patients who were previously enrolled in sponsor-initiated studies of multicentric Castleman's disease (C0328T03 and CNTO328MCD2001) and are either treatment-naive or have not progressed on siltuximab in the opinion of the investigator. Genders Eligible for Study: Both - Have multicentric Castleman's disease - Have previously been enrolled in Study C0328T03 or CNTO328MCD2001 (either treatment arm) - Have had their last administration of study treatment (siltuximab or placebo) less than 6 weeks (window of plus 2 weeks) prior to first dose. Patients with longer treatment durations since the last study treatment may be allowed after discussion with the medical monitor - Patients must not have had disease progression while receiving siltuximab. For those patients originally assigned to placebo in the CNTO328MCD2001 study, patients who have received less than 4 months of siltuximab following crossover will also be eligible - Have adequate clinical laboratory parameters within 2 weeks prior to the first dose of siltuximab for this study Other eligibility criteria may apply. - Unmanageable toxicity, an adverse event, progression of disease, or withdrawal of consent as reason for discontinuing treatment from previous sponsor-initiated siltuximab study - Vaccination with live, attenuated vaccines within 4 weeks of first dose of this study - Intervening treatment for Castleman's disease since the previous siltuximab study except for corticosteroids, provided the dose is not exceeding 1 mg/kg/day of prednisone (or equivalent) and remained stable or decreased over the 4 weeks prior to enrollment - Known unmanageable allergies, hypersensitivity, or intolerance to monoclonal antibodies or to murine, chimeric, or human proteins or their excipients Other exclusion criteria may apply. 71e5156449ee52f56e37b138f8c2d366 8678 A Safety Study of Carfilzomib and Pomalidomide With Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma I Bill Bensinger, MD 2512.00 36; 57 Hematologic Malignancies; Multiple Myeloma (MM) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8678.html http://www.clinicaltrials.gov/ct/search?term=NCT01464034 NCT01464034 This is a dose finding pilot study to evaluate the safety and determine the maximum tolerated dose of the combination of carfilzomib and pomalidomide with dexamethasone (CPD) in patients with relapsed or refractory multiple myeloma. The study will also explore the efficacy of CPD including overall response, time to progression, progression free survival, and time to next therapy. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Cytopathologically or histologically confirmed diagnosis of multiple myeloma - Relapsed or refractory to the most recently received therapy. Refractory disease is defined as = 25% response or progression during therapy or within 60 days after completion. - All patients must have received prior lenalidomide therapy and been determined to be refractory. Refractory will be defined as a history of progression on a regimen containing full or maximally tolerated dose of lenalidomide. - Measurable disease, as indicated by one or more of the following: Serum M-protein = 0.5 g/dL Urine Bence Jones protein = 200 mg/24 hr Elevated Free Light Chain as per IMWG criteria, and abnormal ratio - Prior to enrollment, sites must provide evidence of myeloma progression/relapse and evidence of being refractory to lenalidomide, with start and stop dates of lenalidomide therapy and the most recent treatment regimen, as well as best tumor response to all prior treatment regimens. - Males and females = 18 years of age - Life expectancy of more than 3 months - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 - Adequate hepatic function, with bilirubin < 2 times the upper limit of normal (ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 times ULN - Uric acid, if elevated, must be corrected to within laboratory normal range prior to dosing - Serum creatinine = 2 mg/dL - Creatinine Clearance = 50 mL/min - Additional Laboratory Requirements Absolute neutrophil count (ANC) =1.0 x 109/L Hemoglobin =8 g/dL(transfusion permitted) Platelet count =50.0 x 109/L - Screening ANC should be independent of granulocyte-and granulocyte/macrophage colony stimulating factor (G-CSF and GM-CSF) support for at least 1 week and of pegylated G-CSF for at least 2 weeks - Patients may receive red blood cell (RBC) or platelet transfusions, if clinically indicated, in accordance with institutional guidelines - Screening platelet count should be independent of platelet transfusions for at least 2 weeks. - Written informed consent in accordance with federal, local, and institutional guidelines - Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting pomalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking pomalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. - Male patients must agree to never have unprotected sexual contact with a female who can become pregnant and must agree to either completely abstain from sexual contact with females who are pregnant or are able to become pregnant, or he must use a latex condom every time he engages in sexual contact with females who are pregnant or may become pregnant while he is taking pomalidomide and for 4 weeks after he stops taking the drug, even if he has had a successful vasectomy. The patient must agree to inform his physician if he has had unprotected sexual contact with a female who can become pregnant or if he thinks for any reason that his sexual partner may be pregnant. - Male patients cannot donate semen or sperm while taking pomalidomide and for 28 days after completing the study. - Patients must agree to take enteric-coated aspirin 81 mg orally daily, or if history of prior thrombotic disease, must be fully anticoagulated with warfarin (INR 2-3) or be treated with full-dose, low molecular weight heparin, as if to treat deep venous thrombosis (DVT)/pulmonary embolism (PE) Other eligibility criteria may apply. - Patients with known sensitivity to any immunomodulatory drugs (IMiDs) - Corticosteroid therapy in a dose equivalent to dexamethasone =1.50 mg/day or prednisone =10 mg/day within 3 weeks prior to first dose. (Steroid use is allowed if necessary to treat spinal cord compression.) - Use of any other experimental drug or therapy within 21 days of screening - Exposure to any prior chemotherapy or steroid use within 14 days of screening assessments - Radiation therapy within 14 days of screening - POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) - Plasma cell leukemia - Waldenström's macroglobulinemia - Chemotherapy with approved or investigative anticancer therapeutics, including steroid therapy dose as defined above, within 21 days prior to first dose - Participation in an investigational therapeutic study within 21 days Major surgery within 21 days prior to first dose - Pregnant or lactating females - Congestive heart failure (New York Heart Association class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention or myocardial infarction in the previous six months - Uncontrolled hypertension - Acute active infection requiring systemic antibiotics, antivirals, or antifungals within 14 days prior to first dose - Patients receiving active treatment or intervention for any other malignancy or patients who, at the Investigator's discretion, may require active treatment or intervention for any other malignancy within 8 months of starting study treatment. - Serious psychiatric or medical conditions that could interfere with treatment - Significant neuropathy (Grade 3, Grade 4, or Grade 2 with pain) at the time of the first dose and/or within 14 days before enrollment - Contraindication to any of the required concomitant drugs, including proton-pump inhibitor (e.g. lansoprazole), enteric-coated aspirin or if a history of prior thrombotic disease, warfarin or low molecular weight heparin - Patients in whom the required program of oral and intravenous fluid hydration is contraindicated, e.g. due to pre-existing pulmonary, cardiac, or renal impairment - Patients with primary systemic amyloidosis Other exclusion criteria may apply. a85ba7e3b7e91eb447e32b5fbfae4d12 8692 Phase I Clinical Study of CWP232291 in Acute Myeloid Leukemia Patients I John Pagel, MD, PhD 2513.00 2; 36; 43 Acute Myeloid Leukemia (AML); Hematologic Malignancies; Leukemia Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8692.html http://www.clinicaltrials.gov/ct/search?term=NCT01398462 NCT01398462 CWP232291 inhibits proliferation of cancer cells by blocking the Wnt signaling pathway through promoting the degradation of ß-catenin in cancer cells. It is a small molecule that has demonstrated preclinical activity in a number of cancers including acute myeloid leukemia (AML). Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both Able to understand and willing to sign an informed consent form (ICF) prior to initiation of any study-specific procedure and treatment 18 years of age A pathologically confirmed diagnosis of AML by World Health Organization (WHO) classification that is relapsed or refractory or for which no current therapies are anticipated to result in a durable remission Eastern Cooperative Oncology Group (ECOG) performance score 0-2 In the absence of rapidly progressing disease, the interval from prior treatment to time of study drug administration should be at least 2 weeks for cytotoxic agents or at least 5 half-lives for noncytotoxic agents. If a patient is on hydroxyurea to control peripheral blood leukemic cell counts, the patient must have discontinued hydroxyurea for at least 24 hours before initiation of treatment with study drug. Persistent clinically significant toxicities from prior chemotherapy must not be greater than grade 1 Adequate renal function: - Serum creatinine =/< 2.0mg/dL Adequate hepatic function: - Total bilirubin <1.5 x upper limit of normal (ULN), unless considered due to Gilbert's syndrome - Alkaline phosphatase (AP) =/< 2.5 x ULN - Aspartate transaminase (AST) or alanine transaminase (ALT) =3 x ULN, unless considered due to organ leukemic involvement Women of child-bearing potential (i.e., women who are pre menopausal or not surgically sterile) must use acceptable contraceptive methods (abstinence, intrauterine device [IUD], oral contraceptive, or double barrier device), and must have a negative serum or urine pregnancy test within 2 weeks prior to beginning treatment on this trial. Sexually active men must also use acceptable contraceptive methods for the duration of time on study Able to adhere to the study visit schedule and other protocol requirements Other eligibility criteria may apply. Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure (CHF), cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements Active heart disease including myocardial infarction (MI) within previous 3 months, symptomatic coronary artery disease (CAD), arrhythmias not controlled by medication, or uncontrolled CHF Active central nervous system (CNS) disease Therapy with any other standard or investigational treatment for hematologic malignancy (except hydroxyurea, as mentioned in the inclusion criteria) Therapy with anticoagulant or antithrombotic agents (including aspirin) within 7 days prior to study drug administration History of gastrointestinal (GI) hemorrhage Known positive status for human immunodeficiency virus (HIV) and/or active hepatitis B or C Pregnant or nursing women. Pregnant and nursing patients are excluded because the effects of CWP232291 on a fetus or nursing child are unknown. Patients eligible for bone marrow transplant, regardless of age Patients with FLT3 ITD positive AML or AML patients with other cytogenetic abnormalities who are eligible for trials of other targeted investigational agents from which the investigator feels there is greater benefit. Other exclusion criteria may apply. aa76fceacd9e4d2e7bee7d33db2c2e66 8807 Phase III Study of Lenalidomide and Dexamethasone With or Without Elotuzumab to Treat Newly Diagnosed, Previously Untreated Multiple Myeloma (ELOQUENT - 1) III Bill Bensinger, MD 2521.00 36; 57 Hematologic Malignancies; Multiple Myeloma (MM) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8807.html http://www.clinicaltrials.gov/ct/search?term=NCT01335399 NCT01335399 The purpose of the study is to determine whether the addition of Elotuzumab to Lenalidomide/low-dose Dexamethasone will increase the progression free survival (PFS) - Subjects who are newly diagnosed with symptomatic Multiple Myeloma (MM) and who: - have not received any prior systemic anti-myeloma therapy AND - have measurable disease AND - are not candidates for high-dose therapy plus stem-cell transplantation because of age (= 65 years) or coexisting conditions Other eligibility criteria may apply. - Subjects with non-secretory or oligo-secretory or free light-chain only myeloma - Smoldering MM, defined as asymptomatic MM with absence of lytic bone lesions - Monoclonal Gammopathy of Undetermined Significance (MGUS) - Active plasma cell leukemia - Positive for Hepatitis B, C or Human Immunodeficiency Virus (HIV) Other exclusion criteria may apply. 4fd795915b7c23c842b5a7274f7795b2 8765 Single Agent Ofatumumab Vs. Single Agent Rituximab in Follicular Lymphoma Relapsed After Rituximab-Containing Therapy III David Maloney, MD, PhD 2522.00 36; 48 Hematologic Malignancies; Lymphoma Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8765.html http://www.clinicaltrials.gov/ct/search?term=NCT01200589 NCT01200589 Purpose: This is a multi-center, parallel, active comparator controlled, open-label, randomized (1:1) phase III study of single agent ofatumumab compared to single agent rituximab in subjects with rituximab-sensitive grade 1, 2, and 3A follicular lymphoma that has relapsed at least 6 months after completing treatment with single agent rituximab or a rituximab-containing regimen. Subjects must have attained a Complete Response or Partial Response to their last prior rituximab containing therapy lasting at least six months beyond the end of rituximab therapy. Subjects will receive four weekly doses of single agent ofatumumab (1000 mg) or rituximab (375 mg/m2), followed by ofatumumab (1000 mg) or rituximab (375 mg/m2) every 2 months for four additional doses. Therefore, subjects will receive a total of eight doses of anti-CD20 antibody over 9 months. Subjects will be evaluated for response after completion of the first four doses of therapy, after six doses of therapy, and after completion of study therapy. Subjects will be followed until the end of the designated follow-up period (total study duration of 200 weeks) or until they meet the withdrawal criteria. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Follicular lymphoma (FL); grades 1, 2 and 3A, defined according to World Health Organization guidelines. - Rituximab-sensitive FL, defined as a partial or complete response to treatment with rituximab or a rituximab-containing regimen lasting at least 6 months following completion of the last rituximab treatment. - Relapse or disease progression following response to prior rituximab-based therapy, as defined by 2007 Revised Response Criteria for Malignant Lymphoma criteria, which requires therapy. - Radiographically measurable disease, defined as at least one clearly demarcated lesion with a largest diameter = 2.0 cm by CT scan imaging. - ECOG Performance Status of 0, 1, or 2. - Age = 18 years. - Life expectancy of at least 6 months in the opinion of the investigator. - The patient or their legally acceptable representative must be capable of giving written informed consent prior to performing any study-specific tests or procedures. - All prior treatment related non-hematologic toxicities (with the exception of alopecia) must have resolved to CTCAE (Version 4.0) = Grade 2 at the time of randomization. - French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category. Other eligibility criteria may apply. - Previous treatment with ofatumumab. - Previous radioimmunotherapy (RIT) within 6 months of randomization. Patients who have received previous RIT must have attained a partial or complete response lasting at least 6 months, and must have recovered from any hematologic or other toxicity. - Previous autologous stem cell transplantation within 6 months of randomization. - Previous allogeneic stem cell transplantation. - Previous anti-lymphoma monoclonal antibody therapy (excluding rituximab), chemotherapy, glucocorticoid, or other systemic therapy for lymphoma within 3 months of randomization. - Current or previous participation in another interventional clinical study within 4 weeks of randomization. - Current or previous other malignancy within 2 years of randomization. Subjects who have been free of malignancy for at least 2 years, or have a history of completely resected non-melanoma skin cancer or successfully treated carcinoma in situ, are eligible. - Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis, active Hepatitis C, and known HIV disease. - Clinically significant cardiac disease as judged by the investigator including unstable angina, acute myocardial infarction within 6 months of randomization, congestive heart failure, and arrhythmia requiring therapy. - Other significant concurrent, uncontrolled medical conditions including, but not limited to, renal, hepatic, autoimmune, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease which, in the investigator's opinion, will impact study participation. - Screening laboratory values: Neutrophils < 1.5 x 109/L (unless due to FL involvement of the bone marrow). Platelets < 50 x 109/L (unless due to FL involvement of the bone marrow). ALT or AST > 2xULN, alkaline phosphatase and bilirubin > 1.5xULN (isolated predominantly indirect hyperbilirubinemia due to Gilbert's syndrome is acceptable for inclusion) Known or suspected inability to fully comply with study protocol a. Lactating women. b. Women with a positive pregnancy test at study entry c. Men with partners of childbearing potential and women of childbearing potential who are not willing to use adequate contraception from study entry through one year following last treatment dose. 14. Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones). 15. Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HB DNA test will be performed and if positive the subject will be excluded. Other exclusion criteria may apply. 046ca384f03139d0b867cb3e7b7fab9e 8864 Phase 1/2 Safety and Efficacy of PLX3397 in Adults With Relapsed or Refractory Acute Myeloid Leukemia (AML) I/II John Pagel, MD, PhD 2532.00 2; 36; 43 Acute Myeloid Leukemia (AML); Hematologic Malignancies; Leukemia Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8864.html http://www.clinicaltrials.gov/ct/search?term=NCT01349049 NCT01349049 The purpose of this study is to evaluate the safety of study drug PLX3397 at 3 dose levels (800 mg/day, 1000 mg/day, and 1200 mg/day) and explore the efficacy in patients with relapsed or refractory acute myeloid leukemia (AML). Additional dose levels beyond 1200 mg/day may be considered based on safety and efficacy observations. - Ages Eligible for Study: 18 Years and older - Genders Eligible for Study: Both - Male or female patients =18 years old - Morphologically documented primary Acute Myeloid Leukemia (AML), prior chemotherapy-related AML, or AML secondary to an antecedent hematologic disorder (e.g. MDS), as defined by World Health Organization (WHO) criteria, confirmed by pathology review at the treating institution. Bone marrow involvement is required for Cohort Expansion Phase (Part 2)only. - In at least first relapse or refractory AML; patients = 60 years old can be included if unable or unwilling to undergo induction chemotherapy for hematopoietic stem cell transplantation (HSCT) - Positive for Flt3-ITD activating mutation during Screening - ECOG performance status of 0, 1, or 2 - Adequate recovery (to at least Grade 1) from toxicity of prior therapy as follows: - =2 weeks prior to C1D1 for cytotoxic therapy (excluding hydroxyurea, which is permitted at doses less than or equal to 5 g/day during first 2 weeks of cycle 1) - =4 half-lives for non-cytotoxic therapy prior to C1D1; washout period from last chemotherapy of at least 2 weeks OR at least 4 half-lives prior to C1D1. - Adequate renal and hepatic function - Adequate renal function, defined as Creatinine Clearance > 60 ml/min. - Adequate hepatic function, defined as AST and ALT < 3.0X ULN and serum direct bilirubin < 1.5X ULN. Exceptions may be made for patients with elevated liver transaminases secondary to AML. - Life expectancy of at least 1 month - Willing and able to provide written informed consent prior to any study related procedures and to comply with all study requirements - Women of child-bearing potential must have a negative serum pregnancy test within 7 days of initiation of dosing and must agree to use two acceptable methods of birth control while on study drug and for 3 months after the last dose. Women of non-childbearing potential may be included if they meet at least one of the following criteria: - Surgically sterile - Have been postmenopausal for = 1 year - Have follicle stimulation hormone (FSH) levels indicative of postmenopausal state (i.e. 30-120 IU/L) Sexually active men must also agree to use an acceptable method of birth control while on study drug and for 3 months after last dose. Other eligibility criteria may apply. - Diagnosis of acute promyelocytic leukemia - Diagnosis of chronic myelogenous leukemia in blast crisis - Presence of CNS involvement of leukemia [discuss with Medical Monitor] - Eligible for hematopoietic stell cell transplant (HSCT) at time of screening. However, patients who meet both of the following criteria may be eligible for study participation: - 1. eligible for HSCT but with non-optimal AML disease control (i.e., blasts greater than 5 percent) may be enrolled as bridge-to-transplant. - 2. relapsed disease following prior HSCT may be enrolled as alternative to second HSCT or as bridge-to-transplant regimen. - Receipt of HSCT within 60 days of the first dose of PLX3397, on immunosuppressive therapy post HSCT at the time of Screening, or with clinically significant graft-versus-host disease. [Use of topical steroids for ongoing skin (Graft versus Host Disease) (GVHD) is permitted) - Investigational drug use within 28 days of the first dose of PLX3397 - For Cohort Expansion Phase (Part 2) only: Relapse or refractory disease following treatment with another FLT3 tyrosine kinase inhibitor (TKI). This does NOT include patients who discontinued AC220 or other TKI due to poor tolerability or to undergo HSCT. - Disease positive for D835 mutation at Screening - A concurrent active cancer that requires non-surgical therapy (e.g. chemotherapy, radiation, adjuvant therapy). Prior history of other cancer is allowed, as long as there was no active disease within 1 year. - Refractory nausea and vomiting, malabsorption, biliary shunt, or significant bowel resection that would preclude adequate absorption - Patients with serious illnesses, uncontrolled infection, medical conditions, or other medical history including abnormal laboratory results, which in the investigator's opinion would be likely to interfere with a patient's participation in the study, or with the interpretation of the results - Women of child-bearing potential who are pregnant or breast feeding - QTcF = 450 msec Other exclusion criteria may apply. e7e47d6786821c7e8d9d4f046bbd5275 8983 Randomized Study of ON 01910.Na in Refractory Myelodysplastic Syndrome Patients With Excess Blasts III Bart Scott, MD 2534.00 36; 43; 61 Hematologic Malignancies; Leukemia; Myelodysplastic and Myeloproliferative Syndromes (MDS and MPD) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8983.html http://www.clinicaltrials.gov/ct/search?term=NCT01241500 NCT01241500 The primary objective of this study is to compare overall survival (OS) in patients receiving ON 01910.Na + best supportive care (BSC) to OS of patients receiving BSC in a population of patients with myelodysplastic syndrome (MDS) with excess blasts (5% to 30% bone marrow blasts) who have failed azacitidine or decitabine treatment. This patient population has no available therapy and a short life expectancy (approximately 4 months). The high level of bone marrow activity of ON 01910.Na documented in Phase 1 and 2 studies has the potential to delay substantially the transition of MDS to Acute Myeloid Leukemia(AML), a very significant and severe complication, which shortens survival of these MDS patients. - Ages Eligible for Study: 18 Years and older - Genders Eligible for Study: Both - MDS diagnosis confirmed within 6 weeks prior to entry according to WHO or FAB classification - MDS classified as follows, according to WHO and FAB classification: - RAEB-1 (5% - 9% BM blasts) - RAEB-2 (10% - 20% BM blasts) - CMML (10% - 20% BM blasts) and WBC < 13,000/µL - RAEB-t (21% - 30% BM blasts), with following criteria: - o WBC < 25 x 10E9/L at entry - o Stable WBC at least 4 weeks prior to entry and not requiring intervention for WBC control with hydroxyurea, chemotherapy, or leukopheresis. - At least one cytopenia (ANC < 1800/µL or platelet count < 100,000/µL or hemoglobin <10 g/dL) - Progression according to 2006 International Working Group (IWG) criteria any time after start of azacitidine or decitabine during past 2 years; or failure to achieve complete or partial response or hematological improvement (according to 2006 IWG) after at least six 4-week cycles of azacitidine or four 6-week cycles of decitabine during past 2 years; or relapse after initial complete or partial response or hematological improvement (according to 2006 IWG criteria) observed after at least six 4-week cycles of azacitidine or four 6-week cycles of decitabine during past 2 years; or, intolerance to azacitidine or decitabine defined by drug-related =Grade 3 liver or renal toxicity leading to discontinuation during the past 2 years. - Did not respond to, relapsed after, not eligible for, or opted not to do bone marrow transplantation - Off other MDS treatments for at least 4 weeks; Filgrastim (G-CSF) and erythropoietin allowed before and during the study as clinically indicated. - No need for induction chemotherapy - ECOG status 0, 1 or 2 - Willing to adhere to protocol prohibitions and restrictions - Patient (or a legally authorized representative) must sign informed consent form to indicate patient's understanding study's purpose and procedures and willingness to participate Other eligibility criteria may apply. - Anemia due to factors other than MDS (including hemolysis or gastrointestinal bleeding) unless stabilized for 1 week after RBC transfusion. - Any active malignancy within the past year, except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast - Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia - Active infection not adequately responding to appropriate therapy - Total bilirubin =1.5 mg/dL not related to hemolysis or Gilbert's disease. - Alanine transaminase (ALT)/aspartate transaminase (AST) =2.5 x upper limit of normal (ULN) - Serum creatinine =2.0 mg/dL - Ascites requiring active medical management including paracentesis, or hyponatremia (defined as serum sodium value of <130 mEq/L) - Pregnant or lactating females - Patients unwilling to follow strict contraception requirements (including condom use for males with sexual partners, and for females: prescription oral contraceptives [birth control pills], contraceptive injections, intrauterine device, double-barrier method [spermicidal jelly or foam with condoms or diaphragm], contraceptive patch, or surgical sterilization) before entry and throughout the study - Females with reproductive potential who do not have a negative urine beta-human chorionic gonadotropin pregnancy test at screening - Major surgery without full recovery or major surgery within 3 weeks of ON 01910.Na treatment start - Uncontrolled hypertension (defined as systolic pressure =160 mmHg and/or diastolic pressure =110 mmHg) - New onset seizures (within 3 months prior to first dose of ON 01910.Na) or poorly controlled seizures - Any other concurrent investigational agent or chemotherapy, radiotherapy, or immunotherapy - Prior treatment with low-dose cytarabine during past 2 years Investigational therapy within 4 weeks of starting ON 01910.Na - Psychiatric illness or social situation that limits the patient's ability to tolerate and/or comply with study requirements Other exclusion criteria may apply. 2d692ea901101661d3319f009a0d4761 8803 Intravenous Administration of RGI-2001 in Patient Undergoing Allogenic Hematopoietic Stem Cell Transplantation (AHSCT) I/II Paul Martin, MD 2538.00 1; 2; 36; 38; 61; 64 Acute Lymphoid Leukemia (ALL); Acute Myeloid Leukemia (AML); Hematologic Malignancies; Hodgkin's Lymphoma; Myelodysplastic and Myeloproliferative Syndromes (MDS and MPD); Non-Hodgkin's Lymphoma (NHL) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8803.html http://www.clinicaltrials.gov/ct/search?term=NCT01379209 NCT01379209 This is a first in man clinical trial that is designed as a two part study in patients undergoing AHSCT. RGI-2001 is believed to have immunomodulating effects that may expand regulatory T-cells and other beneficial cells to modulate the intensity of GvHD after the AHSCT procedure. All patients receive study medication. In Part 1 (Dose Escalation Phase), patients will receive a single intravenous administration of RGI-2001 approximately 30 minutes after completion of the AHSCT, with the dosage based upon the assigned treatment cohort and body weight. Eligible patients will be enrolled in up to four to six centers in the United States. Patients who are undergoing Allogenic Hematopoietic Stem Cell Transplantation (AHSCT) will be enrolled in a sequential group dose-escalating fashion to determine the safety, tolerability, pharmacokinetic profile, and the MTD or MFD of RGI-2001. It is anticipated that up to seven dose levels will be evaluated in Part 1, with an option for an additional cohort if the MTD is not reached and pharmacodynamic markers suggest higher doses are warranted. In Part 2 (Expansion Phase), one or more doses below the MTD or MFD will be selected based on a potential correlation between GvHD and biological activity to further assess safety and biologic activity. Approximately 30 patients will be enrolled in Part 2 of the study. Patients will be monitored for safety for 29 days after AHSCT. All patients in part 1 and 2 of this study will be followed for 100 days following AHSCT for the incidence of acute GvHD. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both Patients with hematological malignancies or myelodysplastic syndrome undergoing myeloablative therapy and a first allogeneic HSCT (AHSCT) Male or female, age = 18 years of age Eastern Cooperative Oncology Group (ECOG) status of 0-2 or Karnofsky Performance Status (KPS) of > 60 Part 1 Dose Escalation AHSCT Procedure: 1. Patients with hematological malignancies or myelodysplastic syndrome undergoing a first AHSCT procedure and who are in their 2nd or subsequent remission 2. Type of allograft: Unrelated allogeneic hematopoietic stem cell transplant donor with no more than 1 HLA allele or antigen mismatch. 3. Source of allograft: Unmodified (non-manipulated) bone marrow. 4. Anti-graft versus host disease (GvHD) prophylaxis will include a calcineuron inhibitor [either tacrolimus (FK506) or cyclosporin A)], in combination with either methotrexate (MTX) or mycophenolate mofetil (MMF), all at doses as per the institutional protocols. Part 2 Expansion AHSCT Procedure: 1. Patients with hematological malignancies or myelodysplastic syndrome undergoing a first AHSCT procedure and who are in their 1st (CR1) or subsequent complete remission 2. Type of allograft: Related or unrelated allogeneic hematopoietic stem cell transplant donors with no more than 1 HLA allele or antigen mismatch. 3. Source of allograft: Unmodified (non-manipulated), bone marrow or mobilized peripheral blood stem cell transplant (PBSCT) using G-CSF as the mobilizing agent. 4. Anti-graft versus host disease (GvHD) prophylaxis will include a calcineuron inhibitor [either tacrolimus (FK506) or cyclosporin A)], in combination with either methotrexate (MTX) or mycophenolate mofetil (MMF), all at doses as per the institutional protocols. Other eligibility criteria may apply. Female patients who are pregnant or lactating Patients about to undergo mini allogeneic transplant (also known as reduced intensity transplant, non-ablative or non-myeloablative transplant, or adoptive immunotherapy) Radiation, chemotherapy, immunotherapy in the previous 3 weeks, unrelated to the AHSCT procedure Patient who is about to undergo cord blood transplantation Procedures that are intended to deplete regulatory T-cells from donor transplant materials Known or suspected HIV infection Active hepatitis A, B, or C infection in recipient or donor Prior treatment with anti-thymocyte globulin, anti-CD20, or anti-CD3 antibodies Cardiac pacemaker or automatic implantable cardioverter-defibrillator Prior autologous or allogeneic hematopoietic stem cell transplantation Any other prior organ transplant Other exclusion criteria may apply. 39324302649745c390ecad7e03c92ec0 9043 Previous Study | Return to List | Next Study Low Dose Cytarabine and Lintuzumab-Ac225 in Older Patients I/II John Pagel, MD, PhD 2572.00 2; 36 Acute Myeloid Leukemia (AML); Hematologic Malignancies Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9043.html http://www.clinicaltrials.gov/ct/search?term=NCT01756677 NCT01756677 The goal of the Phase 1 part of this study is to find the highest tolerable dose of Lintuzumab-Ac225 that can be given with cytarabine to patients with acute myeloid leukemia (AML). The goal of the Phase 2 part of this study is to learn if Lintuzumab-Ac225 and cytarabine can control AML. The safety of this drug combination will also be studied. Lintuzumab-Ac225 is designed to deliver radiation therapy directly inside leukemia cells without giving any radiation to the surrounding normal cells Cytarabine is designed to insert itself into DNA (genetic material) of cancer cells and stop the DNA from repairing itself. Ages Eligible for Study: 60 Years and older Genders Eligible for Study: Both - 1. Untreated acute myelogenous leukemia (AML), including patients with an antecedent hematologic disorder or secondary disease. Patients with prior myelodysplastic syndromes (MDS) may have received therapy with immunomodulatory agents or hypomethylating agents for this diagnosis. patients with other prior cancer diagnoses are allowed as long as they ahve no measurable disease are not undergoing active therapy, and have a life expectancy of greater than or equal 4 months. - 2. Patients age greater than or equal to 60 years who: a. Are unwilling to receive intensive (e.g. 7+3) chemotherapy, or b. Have poor-risk prognostic factors defined as antecedent hematologic disorder, prior chemotherapy or chemoradiation therapy (XRT), abnormal karyotype other than t(8;21), inv16, or t(16;16), any karyotype with Internal tandem duplications of Flt3 (Flt3-ITD), or presenting white blood count (WBC) greater than 100K, or c. Have significant comorbidities, that in the judgment of the investigator makes the subject unsuitable for standard dose induction chemotherapy (e.g. anthracycline and infusional cytarabine given as 7+3); or d. Any patient age greater than or equal to 70 years. - 3. Blast count greater than or equal to 20 percent (World Health Organization (WHO) criteria) - 4. Greater than 25 percent of blasts must be CD33 positive. - 5. Creatinine less than 2.0 mg/dl - 6. Estimated creatinine clearance greater than or equal to 50ml/min. - 7. Bilirubin less than or equal to 2.0 mg/dl; aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT) less than or equal to 2.5 times the upper limits of normal (ULN). - 8. Eastern Cooperative Oncology Group (ECOG) Performance status less than or equal to 3. Other eligibility criteria may apply. - 1. Patients with acute promyelocytic leukemia. - 2. Treatment with chemotherapy or biologic therapy within 3 weeks, except for hydroxyurea, which must be discontinued prior to treatment on study - 3. Treatment with radiation within 6 weeks - 4. Active serious infections uncontrolled by antibiotics - 5. Active malignancy within 2 years of entry, except previously treated non-melanoma skin cancer, carcinoma in situ or cervical intraepithelial neoplasia, and organ confined prostate cancer with no evidence of progressive disease based on prostate-specific antigen (PSA) levels and are not on active therapy - 6. Clinically significant cardiac or pulmonary disease - 7. Active central nervous system (CNS) leukemia. Patients with symptoms of CNS involvement, particularly those with M4 or M5 subtypes, should undergo lumbar puncture prior to treatment on study to exclude CNS disease. Symptoms include cranial neuropathies, other neurologic deficits, and headache. - 8. Psychiatric disorder that would preclude study participation Other exclusion criteria may apply. 0c431894f3244e127d715d71bcff47ea 9055 A Study To Evaluate PF-04449913 With Chemotherapy In Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome I/II Vivian Oehler, MD 2592.00 2; 36; 43 Acute Myeloid Leukemia (AML); Hematologic Malignancies; Leukemia Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9055.html http://www.clinicaltrials.gov/ct/search?term=NCT01546038 NCT01546038 This is a study to evaluate PF-04449913 (an inhibitor of the Hedgehog pathway) in Acute Myeloid Leukemia and high-risk Myelodysplastic Syndrome in combination with standard agents used to treat these diseases. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Patients with AML or RAEB 2 High Risk MDS who are newly diagnosed according to the WHO 2008 Classification and previously untreated. - Patients with AML (arising from an antecedent hematologic disease [AHD]) or MDS who may have had one prior regimen with commercially available agents for the treatment of their prior hematologic disease. The patients may not have had a prior therapy for their AML. - AML patients include de novo AML, AML evolving from MDS or other AHD and AML after previous cytotoxic therapy or radiation (secondary AML) - For a diagnosis of AML, a bone marrow blast count of 20% or more is required. - For a diagnosis of high-risk Myelodysplastic Syndrome RAEB 2 the patient must have 10-19% bone marrow blasts - Adequate Organ Function - ECOG Performance Status 0, 1, or 2 Other eligibility criteria may apply. - AML M3 Acute Promyelocytic Leukemia (APL) or patients with a t(9:22) cytogenetic translocation. - Patients in whom, at the time of study entry, a stem cell transplant is planned within the next 6 months. - Patients with known active uncontrolled central nervous system (CNS) leukemia. Other exclusion criteria may apply. 350cfb15616777f2ddd8b7d348471547 9228 A Randomized, Double-Blind and Placebo-Controlled Study of GS-1101 in Combination With Bendamustine and Rituximab for Previously Treated Chronic Lymphocytic Leukemia (CLL) III John Pagel, MD, PhD 2597.00 18; 36; 43 Chronic Lymphoid Leukemia (CLL); Hematologic Malignancies; Leukemia Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9228.html http://www.clinicaltrials.gov/ct/search?term=NCT01569295 NCT01569295 The purpose of this study is to evaluate the effect of GS-1101 on the onset, magnitude, and duration of tumor control. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Previously treated recurrent CLL - Measurable lymphadenopathy - Requires therapy for CLL - Has experienced CLL progression <36 months since the completion of the last prior therapy Other eligibility criteria may apply. - Recent history of a major non-CLL malignancy - Evidence of an ongoing infection - CLL refractory to bendamustine - Concurrent participation in another therapeutic clinical trial Other exclusion criteria may apply. bcbc1103a51ec68e1b739e566481ea80 9360 A Safety Study of Carfilzomib With Cyclophosphamide and Dexamethasone Prior to Autologous Stem Cell Transplant in Patients With Newly Diagnosed Multiple Myeloma (11-MM-01) I Bill Bensinger, MD 2599.00 57 Multiple Myeloma (MM) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9360.html http://www.clinicaltrials.gov/ct/search?term=NCT01660750 NCT01660750 This is a dose finding pilot study to evaluate the safety and determine the maximum tolerated dose of the combination of carfilzomib and cyclophosphamide with dexamethasone (Car-Cy-Dex) prior to autologous stem cell transplant (ASCT) in patients with newly diagnosed transplant eligible multiple myeloma. The study will also explore the efficacy of Car-Cy-Dex including overall response after induction therapy, overall response at 3 and 6 months post ASCT, and time to progression, progression free survival, and time to next therapy if it occurs within 6 months post ASCT. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Cytopathologically or histologically confirmed diagnosis of MM - Measurable disease, as indicated by one or more of the following: - Serum M-protein = or> 1.0 g/dL - Urine Bence Jones protein = or> 200 mg/24 hr - Elevated Free Light Chain as per the International Myeloma Working Group (IMWG) criteria - Males and females = or> 18 years of age - Life expectancy of more than 5 months - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 - Adequate hepatic function, with bilirubin < 2 times the upper limit of normal (ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3.5 times ULN - Serum Creatinine Clearance(CrCl) = or> 30 mL/min, either measured or calculated using a standard formula (e.g. Cockcroft and Gault) - Additional Laboratory Requirements - Absolute neutrophil count (ANC) = or>1.0 x 109/L - Hemoglobin = or> 8 g/dL [transfusion permitted] - Platelet count = or> 50.0 x 109/L - Screening ANC should be independent of granulocyte-and granulocyte/macrophage colony stimulating factor (G-CSF and GM-CSF) support for at least 1 week and of pegylated G-CSF for at least 2 weeks - Patients may receive RBC or platelet transfusions, if clinically indicated, in accordance with institutional guidelines - Written informed consent in accordance with federal, local, and institutional guidelines - Patients must agree to practice contraception - Male patients must agree not to donate semen or sperm. Other eligibility criteria may apply. - Patients with non-secretory or hyposecretory MM - Prior treatment for MM (prior radiation therapy or dexamethasone up to 160 mg for spinal cord compression is allowed. Other limited field radiation involving = or > 1/3 of the pelvic area is also allowed) - Plasma cell leukemia - Pregnant or lactating females - Major surgery within 21 days prior to first dose - Congestive heart failure (CHF) (New York Heart Association class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention or myocardial infarction in the previous six months - Acute active infection requiring systemic antibiotics, antivirals, or antifungals within 14 days prior to first dose - Patients receiving active treatment or intervention for any other malignancy or patients who, at the Investigator's discretion, may require active treatment or intervention for any other malignancy within 8 months of starting study treatment. - Serious psychiatric or medical conditions that could interfere with treatment - Significant neuropathy (Grade 3, Grade 4, or Grade 2 with pain) at the time of the first dose and/or within 14 days before study treatment - Contraindication to any of the required concomitant drugs, including antiviral (e.g. Valacyclovir) and proton-pump inhibitor (e.g. lansoprazole). Corticosteroid therapy in a dose equivalent to dexamethasone = or> 1.5 mg/day or prednisone = or> 10 mg/day. (Steroid use is allowed if necessary to treat spinal cord compression and/or hypocalcaemia.) - Patients in whom the required program of oral and IV fluid hydration is contraindicated, e.g. due to pre-existing pulmonary, cardiac, or renal impairment - Patients with primary systemic amyloidosis. Other exclusion criteria may apply. 83df1fe41d706fdbd60ee5e8e7e18e01 9077 Maribavir for Treatment of Resistant or Refractory CMV Infections in Transplant Recipients II Michael Boeckh, MD 2601.00 83; 122 Solid Tumors; Cytomegalovirus (CMV) Louise Kimball lkimball@fhcrc.org 206/667-2904 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9077.html http://www.clinicaltrials.gov/ct/search?term=NCT01611974 NCT01611974 This study will assess safety, antiviral activity, and pharmacokinetics of different doses of maribavir administered orally for up to 24 weeks for treatment of CMV infections that are resistant or refractory to treatment with ganciclovir/valganciclovir or foscarnet in recipients of stem cell or solid organ transplants. Ages Eligible for Study: 12 Years and older Genders Eligible for Study: Both - 1.Be = or>12 years of age. - 2.Weigh = or > 40 kg. - 3.Be a recipient of stem cell or solid organ transplantation. - 4.Have documented CMV infection in blood or plasma, with a screening value of = or >1,000 DNA copies/mL. - 5.Have a current CMV infection that is resistant (known CMV genetic mutations) or refractory (clinical failure to respond) to treatment with ganciclovir/valganciclovir and/or foscarnet. - 6.If female, be either postmenopausal, surgically sterile, or have a negative pregnancy test prior to randomization. - 7.Be able to swallow tablets. - 8.If adult, provide written informed consent. If child (age <18 years), have a parent/legal guardian who is willing and able to provide written informed consent (with assent from the child when appropriate). Other eligibility criteria may apply. - 1.Be receiving any other anti-CMV agent(s). - 2.Have a current CMV infection that is considered resistant or refractory due to inadequate adherence to prior oral anti-CMV treatment. - 3.Have severe vomiting, diarrhea, or other severe gastrointestinal illness within 24 hours prior to the time of enrollment. - 4.Have severe hepatic impairment. - 5.Require mechanical ventilation or vasopressors for hemodynamic support at the time of enrollment. - 6.Have expected survival less than 6 weeks. - 7.Be pregnant or breastfeeding. - 8.Other clinically significant medical or surgical condition. Other exclusion criteria may apply. b98f1c5571c2e8ac8e1f806d2f2490fe 9181 A Phase 3 Study Comparing Oral MLN9708 Plus Lenalidomide and Dexamethasone Versus Placebo Plus Lenalidomide and Dexamethasone in Adult Patients With Relapsed and/or Refractory Multiple Myeloma III Bill Bensinger, MD 2606.00 36; 57 Hematologic Malignancies; Multiple Myeloma (MM) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9181.html http://www.clinicaltrials.gov/ct/search?term=NCT01564537 NCT01564537 The purpose of this phase 3, randomized, double-blind, multicenter study is to compare Oral MLN9708 plus Lenalidomide and Dexamethasone versus Placebo plus Lenalidomide and Dexamethasone in adult patients with relapsed and/or refractory multiple myeloma. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Male or female patients 18 years or older - Diagnosed Multiple Myeloma according to standard criteria - Measurable disease as specified in study protocol - Eastern Cooperative Oncology Group (ECOG)performance status of 0 to 2 - Patients with relapsed and/or refractory Multiple Myeloma who have received 1 to 3 prior therapies - Meet the clinical laboratories criteria as specified in the protocol - Patients who received prior allogenic transplant must have no active graft-versus-host disease (GVHD) - Female patients who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or agree to abstain from heterosexual intercourse; must also adhere to the guidelines of the lenalidomide pregnancy prevention program - Male patients who agree to practice effective barrier contraception or agree to abstain from heterosexual intercourse AND must adhere to the guidelines of the lenalidomide pregnancy prevention program - Must be able to take concurrent aspirin 325 mg daily - Voluntary written consent Other eligibility criteria may apply. - Patient who were refractory to lenalidomide or proteasome inhibitor-based therapy - Female patients who are lactating or pregnant - Major surgery or radiotherapy within 14 days before randomization - Infection requiring systematic antibiotics within 14 days before the first dose of study drug - Central nervous system involvement - Failure to have fully recovered from the effects of prior chemotherapy regardless of the interval since last treatment - Systemic treatment with strong inhibitors of CYP1A2, strong inhibitors of CYP3A, or strong CYP3A inducers, or use of Ginko biloba or St. John's wort within 14 days before the first dose of study treatment - Diagnosis of Waldenstrom's macroglobulinemia, POEMS syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome - Evidence of current uncontrolled cardiovascular conditions - Serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to the protocol - Known allergy to any of the study medications - Known gastrointestinal condition or procedure that could interfere with swallowing or the oral absorption of tolerance of MLN9708 - Diagnosed or treated for another malignancy within 2 years before randomization or previously diagnosed with another malignancy and have any evidence of residual disease with the exception of nonmelanoma skin cancer or any completely resected carcinoma in situ - Ongoing or active systemic infection, active hepatitis B virus infect, active hepatitis C infection, or known human immunodeficiency virus (HIV) positive Other exclusion criteria may apply. de430435e429a4705b67f23afce5c3d9 9182 A Randomized, Double-Blind and Placebo-Controlled Study of GS-1101 in Combination With Rituximab for Previously Treated Chronic Lymphocytic Leukemia (CLL) III John Pagel, MD, PhD 2612.00 18; 36; 43 Chronic Lymphoid Leukemia (CLL); Hematologic Malignancies; Leukemia Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9182.html http://www.clinicaltrials.gov/ct/search?term=NCT01539512 NCT01539512 The purpose of this study is to evaluate the effect of GS-1101 on the onset, magnitude, and duration of tumor control. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Adult subjects with previously treated recurrent CLL who have measurable lymphadenopathy - Require therapy for CLL - Have experienced CLL progression <24 months since the completion of the last prior therapy - Currently not sufficiently fit to receive cytotoxic therapy because of chemotherapy-induced bone marrow damage or comorbidities. Other eligibility criteria may apply. Other exclusion criteria may apply. 9dfc6266a61e5bf09cbac1e4d686184f 9196 A Extension Study of GS-1101 for Patients With Chronic Lymphocytic Leukemia Who Participated in GS-US-312-0116 III John Pagel, MD, PhD 2613.00 18; 36; 43 Chronic Lymphoid Leukemia (CLL); Hematologic Malignancies; Leukemia Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9196.html http://www.clinicaltrials.gov/ct/search?term=NCT01539291 NCT01539291 A companion study to GS-US-312-0116: To evaluate the effect of GS-1101 on the onset, magnitude, and duration of tumor control. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Subjects in the primary Phase 3 study (Study GS-US-312-0116) who are compliant - Tolerating primary study therapy - Have definitive progression of CLL while receiving primary study drug therapy (GS 1101/placebo). Other eligibility criteria may apply. Other exclusion criteria may apply. 3bca7dbbdb5463c7621b0c06ac607507 9333 A Study of CSL362 in Patients With CD123+ Acute Myeloid Leukemia Currently in Remission I Roland Walter, MD 2616.00 2; 36; 43 Acute Myeloid Leukemia (AML); Hematologic Malignancies; Leukemia Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9333.html http://www.clinicaltrials.gov/ct/search?term=NCT01632852 NCT01632852 This is a first in human, prospective, multicenter, nonrandomized, open-label, dose-escalation study to investigate the safety, pharmacokinetics, pharmacodynamics and immunogenicity of repeat doses of CSL362. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Male or female aged 18 years or older. - Previous diagnosis of CD123+ acute myeloid leukemia (AML), de novo or secondary. - Completed and recovered from all planned induction and consolidation therapy according to the institution's standard of care, and achieved a complete remission (CR)/CR with incomplete platelet recovery (CRp); either first or second CR. - Has factors conferring high risk of relapse. - No plans for additional post-remission chemotherapy. - Not currently a candidate for allogeneic hematopoietic stem cell transplant (HSCT). Other eligibility criteria may apply. - Diagnosis of acute promyelocytic leukemia (APL). - Known leukemic involvement of the central nervous system. - Life expectancy 4 months or less as estimated by the investigator. - Concurrent treatment or planned treatment with other anticancer therapy (chemotherapy, immunotherapy, radiotherapy, targeted therapy, gene therapy). Other exclusion criteria may apply. 47b32a507a3bb239d394200a5f0c93ba 9325 An Open Label Study to Evaluate the Safety and Efficacy of Two Doses of Quizartinib in Patients With Relapsed or Refractory Acute Myeloid Leukemia II John Pagel, MD, PhD 2623.00 2; 36; 43 Acute Myeloid Leukemia (AML); Hematologic Malignancies; Leukemia Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9325.html http://www.clinicaltrials.gov/ct/search?term=NCT01565668 NCT01565668 This study will evaluate two doses of Quizartinib in patients with relapsed or refractory acute myeloid leukemia who are also FMS-like tyrosine kinase - internal tandem duplication ( FLT3-ITD) positive. Patient will be randomly assigned in a 1:1 ratio to one of two treatment arms. Both treatment arms will receive Quizartinib but at different doses. The study treatment is taken orally in 28 day cycles until either disease progression occurs or an unacceptable toxicity occurs. In addition to the study assessments to evaluate the disease, blood will be drawn to measure drug levels and biomarkers. Patients will be followed for survival at three month intervals after the end of treatment. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Subject has morphologically documented primary AML or AML secondary to myelodysplastic syndrome (MDS) as defined by the World Health Organization (WHO) criteria, as determined by pathology review at the treating institution and has relapsed or is refractory after 1 second line (salvage) regimen or after HSCT - Subject is positive for FLT3-ITD activating mutation in bone marrow or peripheral blood (>10% allelic ratio) - ECOG performance status of 0 to 2 - In the absence of rapidly progressing disease clearly documented by the investigator, the interval from prior treatment to time of AC220 administration will be at least 2 weeks (14 days) for prior cytotoxic agents or at least 5 half-lives for prior noncytotoxic agents, including immunosuppressive therapy post HSCT - Persistent chronic clinically significant nonhematological toxicities from prior treatment (including chemotherapy, kinase inhibitors, immunotherapy, experimental agents, radiation, HSCT, or surgery) must be Grade = or < than 1 - Patients - both males and females - with reproductive potential are eligible if the following criteria is met: --- Female subject is: --- Post-menopausal (defined as at least 2 years without menses) prior to Screening visit; or --- surgically sterile (at least 1 month prior to Screening visit; or --- of childbearing potential with contraception --- Female subject of childbearing potential has a negative pregnancy test at the Screening visit and agrees to use contraception consisting of two forms of birth control (one of which must be a barrier method) throughout the study period --- Male subject with partner(s) of childbearing potential must agree to use contraception consisting of two forms of birth control (one of which must be a barrier method) and agrees to no sperm donation throughout the study period - Subject must have adequate renal, hepatic, and coagulation parameters as indicated by the following laboratory values: --- Aspartate aminotransferase (AST), and alanine aminotransferase (ALT) = or < 2.5 x institutional upper limit of normal (ULN) --- Total bilirubin = or < 1.5 x institutional ULN --- Serum creatinine = or< 1.5 x institutional ULN and glomerular filtration rate (GFR) > 30 mL/min (calculated by Cockcroft and Gault formula). Other eligibility criteria may apply. - Subject received previous treatment with AC220 - Subject has a diagnosis of acute promyelocytic leukemia - Subject has a diagnosis of chronic myelogenous leukemia (CML) in blast crisis - Subject has AML or antecedent MDS secondary to prior chemotherapy - Subject has had HSCT and has either of the following: --- Is within 100 days of transplant --- Is still taking immunosuppressive drugs --- Has clinically significant graft-versus-host disease requiring treatment --- Has Grade > 1 persistent non hematological toxicity related to the transplant - Donor lymphocyte infusion (DLI) is not permitted during the study or < 30 days prior to study entry - Subject has clinically active CNS leukemia. A subject is considered eligible if CNS leukemia is controlled and subject is receiving intrathecal (IT) therapy at study entry. Subjects should continue to receive IT therapy (or cranial radiation) as clinically indicated - Subject has received concurrent chemotherapy, immunotherapy, or radiotherapy within 14 days prior to the first dose of AC220, or any ancillary therapy that is considered to be investigational (i.e., used for non-approved indications(s) and in the context of a research investigation) within 30 days or 5 half-lives (whichever is longer) prior to the first dose of study drug - Subject requires treatment with concomitant drugs that prolong QT/QTc interval or with strong inhibitors or inducers of cytochrome P450- isozyme3A4 (CYP3A4) with the exception of antibiotics, antifungals, and antivirals that are used as standard of care post-transplant or to prevent or treat infections and other such drugs that are considered absolutely essential for the care of the subject - Subject requires treatment with anticoagulant therapy - Subject has a known positive test for human immunodeficiency virus, hepatitis C, or hepatitis B surface antigen - Subject had major surgery within 4 weeks prior to first dose of AC220 - Subject has uncontrolled or significant cardiovascular disease, including --- A myocardial infarction 12 months prior to the start of study drug; --- Uncontrolled angina within 6 months prior to the start of study drug; --- History of congestive heart failure (CHF) New York Heart Association (NYHA) class 3 or 4. If a screening echocardiogram (ECHO) or Multiple Gate Acquisition Scan (MUGA) is performed within 1 month prior to, or during study screening, and the result is a left ventricular ejection fraction (LVEF) that is = 45% (or institutional lower limit of normal value); then this is not exclusionary --- Heart rate <50 beats per minute at Screening ECG; --- Diagnosed or suspected congenital long QT syndrome; --- Known family history of congenital long QT syndrome; --- QTc interval calculated by Fridericia's correction factor (QTcF) at Screening = to or > 450 ms. The QTcF will be derived from the average QTcF in triplicate; --- Any history of second or third degree heart block; --- Uncontrolled hypertension defined as systolic blood pressure = or > 180 mmHg or diastolic blood pressure = or > 110 mmHg; --- Obligate need for a cardiac pacemaker or defibrillator; --- Complete left bundle branch block; --- Atrial fibrillation documented within 2 weeks prior to first dose of study drug; or --- History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia) that was symptomatic or required treatment (CTCAE Grade 3) - Subject has a pre-existing disorder predisposing the subject to a serious or life-threatening infection (e.g. cystic fibrosis, congenital or acquired immunodeficiency, bleeding disorder, or cytopenias not related to AML) - Subject has an active uncontrolled acute or chronic systemic fungal, bacterial, viral, or other infection - Subject has any of the following laboratory values: --- Serum potassium < 4.0 mmol/L despite supplementation, or > 5.5 mmol/L --- Serum magnesium below the institutional normal limit despite supplementation, or > 3 mg/dL (1.23 mmol/L) --- Serum calcium >11.5 mg/dL (2.9 mmol/L) or ionized calcium >1.5 mmol/L - Subject is a female with a positive pregnancy test, pregnant, or breastfeeding - Subject has any medical, psychiatric, addictive or other kind of disorder which compromises the ability of the subject to give written informed consent and/or to comply with procedures Other exclusion criteria may apply. b3fdf27c350fe0665f06ebbb6db3d2c9 9378 Phase 1b Safety and Efficacy Study of TRU-016 and Rituximab in Previously Untreated Chronic Lymphocytic Leukemia I John Pagel, MD, PhD 2631.00 43; 48; 49 Leukemia; Lymphoma; Lymphoproliferative Disease Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9378.html http://www.clinicaltrials.gov/ct/search?term=NCT01644253 NCT01644253 The purpose of this study is to evaluate the safety and efficacy of TRU-016 when when administered in combination with rituximab in patients with previously untreated chronic lymphocytic leukemia (CLL). Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Diagnosis of CLL by IWCLL criteria and with Rai stage intermediate or high risk CLL - No prior therapy for CLL - At least one of the following criteria for active disease requiring treatment: progressive splenomegaly and/or lymphadenopathy; anemia or thrombocytopenia due to bone marrow involvement; or progressive lymphocytosis with an increase of >50% over a 2-month period or an unanticipated doubling time of less than 6 months - Contraindication to chemotherapy as first-line therapy due to patient age, comorbidity or patient preference - Age >/= to 18 years - ECOG performance status of </= 2 - Life expectancy > 6 months in opinion of Investigator - Serum creatinine, total bilirubin, ALT/SGPT </= 2.0 x upper limit of normal - ANC >/= 800/mm3 - Platelets >/= 30,000/mm3 Other eligibility criteria may apply. - Has received treatment with rituximab, alemtuzumab, ofatumumab or any other chemotherapeutic agent for CLL - Has received an investigational therapy within 30 days of first dose of study drug - Previous or concurrent additional malignancy - Clinically significant pulmonary dysfunction, active infection, prior allogeneic bone marrow transplant, active autoimmune disease - Positive serology for HIV or hepatitis C - Hepatitis B surface antigen or hepatitis B core antibody positive - Pregnant or breastfeeding - Known current drug or alcohol abuse Other exclusion criteria may apply. 4a2978009315423b1356374a653987df 9402 Safety and Efficacy of Fidaxomicin Versus Placebo for Prophylaxis Against Clostridium Difficile-Associated Diarrhea in Adults Undergoing Hematopoietic Stem Cell Transplantation (DEFLECT-1) III Steven Pergam, MD 2634.00 36 Hematologic Malignancies Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9402.html http://www.clinicaltrials.gov/ct/search?term=NCT01691248 NCT01691248 The objective of this study is to demonstrate the efficacy and safety of fidaxomicin versus placebo for prophylaxis against Clostridium difficile-Associated Diarrhea (CDAD) in adult subjects undergoing hematopoietic stem cell transplantation (HSCT). Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Male or female 18 years of age or older. - Female subjects of childbearing potential must be using an adequate and reliable method of contraception (e.g., abstinence, barrier with additional spermicide foam or jelly, intrauterine device, hormonal contraception). Subjects (both male and female) must agree to avoid conception during treatment and for four weeks following the end of study treatment. - Individuals undergoing HSCT with fluoroquinolone prophylaxis. - Informed consent is provided. Other eligibility criteria may apply. - Ongoing active CDAD infection (as evidenced by clinical signs of diarrhea along with the presence of either toxin A and/or B [or their respective genes, tcdA and/or tcdB] of C. difficile in the stool) or current treatment for CDAD. - Undergoing cord blood transplants. - Subject has fulminant colitis, toxic megacolon, or ileus. - A history of inflammatory bowel disease (ulcerative colitis or Crohn's disease). - Women who are pregnant or are actively breast feeding (all women of childbearing potential must have a negative pregnancy test result prior to dosing study drug). - Use of any drugs potentially useful in the treatment of CDAD (e.g. oral vancomycin, metronidazole, oral bacitracin, fusidic acid, rifaximin, and nitazoxanide). - Any other condition that, in the opinion of the investigator, would jeopardize the safety or rights of the subject participating in the study, would make it unlikely for the subject to complete the study, or would confound the results of the study. - Participation in other clinical research studies utilizing an investigational agent within one month prior to screening and during the study treatment period. Other exclusion criteria may apply. 441e64f25cec5bb7094dc873b4470f36 9411 Ponatinib in Newly Diagnosed Chronic Myeloid Leukemia (CML) (EPIC) III Vivian Oehler, MD 2645.00 19; 36 Chronic Myeloid Leukemia (CML); Hematologic Malignancies Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9411.html http://www.clinicaltrials.gov/ct/search?term=NCT01650805 NCT01650805 The purpose of this study is to compare the efficacy of ponatinib and imatinib in patients with newly diagnosed chronic myeloid leukemia (CML) in the chronic phase. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - 1. CP CML within 6 months of diagnosis --- CP-CML will be defined by (i) <15% blasts in bone marrow; (ii) <30% blasts plus promyelocytes in bone marrow; (iii) <20% basophils in peripheral blood; (iv) =/> 100 × 10^9/L platelets (=/> 100,000/mm^3); (v) No evidence of extramedullary disease except hepatosplenomegaly; AND (vi) No prior diagnosis of AP-CML or BP-CML - 2. Cytogenetic assessment must demonstrate the BCR-ABL fusion by presence of the t(9;22) Philadelphia chromosome --- (a)Variant translocations are only allowed provided they are assessable for cytogenetic response utilizing conventional cytogenetic techniques; (b) Conventional chromosome banding must be performed; AND (c) A minimum of 20 metaphases must be assessable at entry - 3. ECOG Performance Status of 0, 1, or 2 - 4. Adequate hepatic function as defined by the following criteria: --- (a) Total serum bilirubin =/< 1.5 x upper limit of normal (ULN), unless due to Gilbert's syndrome; (b) Alanine aminotransferase (ALT) =/< 2.5 × ULN; AND (c) Aspartate aminotransferase (AST) =/< 2.5 × ULN - 5. Adequate renal function as defined as defined by serum creatinine <1.5 x ULN - 6. Adequate pancreatic function as defined by serum lipase and amylase =/< 1.5 × ULN Other eligibility criteria may apply. - 1. Received prior imatinib therapy - 2. Received prior dasatinib therapy - 3. Received prior nilotinib therapy - 4. Received, for CML, any other systemic anticancer therapy, experimental therapy, or radiation therapy with the exception of anagrelide or hydroxyurea - 5. Major surgery within 28 days prior to initiating therapy - 6. History of bleeding disorder unrelated to CML - 7. History of acute pancreatitis within 1 year of study or history of chronic pancreatitis - 8. History of alcohol abuse - 9. Have uncontrolled hypertriglyceridemia (triglycerides >450 mg/dL) - 10. Significant uncontrolled or active cardiovascular disease, specifically including, but not restricted to: --- (a) Myocardial infarction, unstable angina and/or congestive heart failure within 3 months prior to randomization; OR (b) History of clinically significant (as determined by the treating physician) atrial arrhythmia or any ventricular arrhythmia - 11. Uncontrolled hypertension (diastolic blood pressure >100 mm Hg; systolic >150 mm Hg) - 12. Taking medications that are known to be associated with Torsades de Pointes - 13. Ongoing or active infection. The requirement for intravenous (IV) antibiotics is considered active infection - 14. Known history of human immunodeficiency virus (HIV). Testing is not required in the absence of history - 15. Pregnant or breastfeeding - 16. Malabsorption syndrome or other gastrointestinal illness that could affect oral absorption of study drugs - 17. Diagnosed with or received anticancer therapy for another primary malignancy within 3 years prior to entry (except for non-melanoma skin cancer or cervical cancer in situ) - 18. Any condition or illness that, in the opinion of the Investigator, would compromise patient safety or interfere with the evaluation of the drug Other exclusion criteria may apply. 48b12ba0d70d0f351ddc10077e14805c 9390 A Study of DCDT2980S in Combination With MabThera/Rituxan or DCDS4501A in Combination With MabThera/Rituxan in Patients With Non-Hodgkin's Lymphoma II Oliver Press, MD, PhD 2649.00 48; 49; 64 Lymphoma; Lymphoproliferative Disease; Non-Hodgkin's Lymphoma (NHL) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9390.html http://www.clinicaltrials.gov/ct/search?term=NCT01691898 NCT01691898 This randomized, multicenter, open-label study will evaluate the safety and the efficacy of DCDT2980S in combination with MabThera/Rituxan (rituximab) or DCDS4501A in combination with MabThera/Rituxan in patients with relapsed or refractory follicular non-Hodgkin's lymphoma and relapsed/refractory diffuse large B-cell lymphoma. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2 - Life expectancy of at least 12 weeks - History of histologically documented relapsed or refractory Grades 1-3a follicular lymphoma, or relapsed or refractory diffuse large B-cell lymphoma - Availability of an archival or freshly biopsied tumor tissue sample must be confirmed for study enrollment - Have a clinical indication for treatment as determined by the investigator - Must have at least one bi-dimensionally measurable lesion (>1.5 cm in its largest dimension by CT scan or MRI) Other eligibility criteria may apply. - Prior use of any monoclonal antibody, radioimmuno-conjugate or antibody drug conjugate within 4 weeks before study start - Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or any investigational anti-cancer agent within 2 weeks prior study start - Adverse events except for sensory neuropathy from any previous treatments must be resolved or stabilized to Grade </=2 prior study start - Completion of autologous stem cell transplant within 100 days prior study start - Prior allogeneic stem cell transplant - Eligibility for autologous SCT (patients with relapsed or refractory DLBCL) - History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins) - History of other malignancy that could affect compliance with the protocol or interpretation of results - Current or past history of CNS lymphoma - Current Grade > 1 peripheral neuropathy Other exclusion criteria may apply. 2b33addbee322304b46dd7c436fd3f43 9403 Phase III Study of CPX-351 Versus 7+3 in Patients 60-75 Years Old With Untreated High Risk (Secondary) Acute Myeloid Leukemia (301) III John Pagel, MD, PhD 2651.00 2; 36 Acute Myeloid Leukemia (AML); Hematologic Malignancies Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9403.html http://www.clinicaltrials.gov/ct/search?term=NCT01696084 NCT01696084 To confirm the efficacy of CPX-351 compared to 7+3 as first line therapy in elderly patients (60-75 yrs) with high risk (secondary) Acute Myeloid Leukemia. The primary efficacy endpoint will be overall survival. Ages Eligible for Study: 60 Years to 75 Years Genders Eligible for Study: Both - Ability to understand and voluntarily give informed consent - Age 60-75 years at the time of diagnosis of AML - Pathological diagnosis of AML according to WHO criteria (with at least 20% blasts in the peripheral blood or bone marrow) - Confirmation of: --- Therapy related AML: t-AML must have a documented history of prior cytotoxic therapy or ionizing radiotherapy for an unrelated disease --- AML with a history of myelodysplasia: MDSAML must have bone marrow documentation of prior MDS --- AML with a history of CMMoL: CMMoLAML must have bone marrow documentation of prior CMMoL --- De novo AML with karyotypic abnormalities characteristic of MDS: de novoAML must have cytogenetics with abnormalities per WHO. - Eastern Cooperative Oncology Group (ECOG) performance status 0-2 - Able to adhere to the study visit schedule and other protocol requirements - Laboratory values fulfilling the following: --- Serum creatinine < 2.0 mg/dL --- Serum total bilirubin < 2.0 mg/dL, patients with Gilbert's Syndrome should contact the medical monitor --- Serum alanine aminotransferase or aspartate aminotransferase < 3 times the ULN ***Note: If elevated liver enzymes, above the ULN, are related to disease; contact medical monitor to discuss. - Cardiac ejection fraction -/> 50% by echocardiography or MUGA - Patients with second malignancies in remission may be eligible if there is clinical evidence of disease stability for a period of greater than 6 months off cytotoxic chemotherapy, documented by imaging, tumor marker studies, etc., at screening. Patients maintained on long-term non-chemotherapy treatment, e.g., hormonal therapy, are eligible. Other eligibility criteria may apply. - Except for CMMoL, patients with history of myeloproliferative neoplasms (MPN) (defined as a history of essential thrombocytosis or polycythemia vera, or idiopathic myelofibrosis prior to the diagnosis of AML) or combined MDS/MPN are not eligible. - Acute promyelocytic leukemia [t(15;17)] or favorable cytogenetics, including t(8;21) or inv16 if known at the time of randomization. - Clinical evidence of active CNS leukemia - Patients with active (uncontrolled, metastatic) second malignancies are excluded. - 5.1.2.5 Prior treatment intended for induction therapy of AML; only hydroxyurea is permitted for control of blood counts. For example, a patient with MDS that changes HMA dose and schedule after the diagnosis of AML is excluded. AML-type therapy, such as cytarabine alone (>1g/m2/day) or cytarabine plus an anthracycline as well as prior HSCT are also excluded. - Administration of any therapy for MDS (conventional or investigational) must be completed by 2 weeks prior to of the first dose of study drug; in the event of rapidly proliferative disease use of hydroxyurea is permitted until 24 hours before the start of study treatment. Toxicities associated with prior MDS therapy must have recovered to grade 1 or less prior to start of treatment. - Any major surgery or radiation therapy within four weeks. - Patients with prior cumulative anthracycline exposure of greater than 368 mg/m2 daunorubicin (or equivalent). - Any serious medical condition, laboratory abnormality or psychiatric illness that would prevent obtaining informed consent - Patients with myocardial impairment of any cause (e.g. cardiomyopathy, ischemic heart disease, significant valvular dysfunction, hypertensive heart disease, and congestive heart failure) resulting in heart failure by New York Heart Association Criteria (Class III or IV staging) - Active or uncontrolled infection. Patients with an infection receiving treatment (antibiotic, antifungal or antiviral treatment) may be entered into the study but must be afebrile and hemodynamically stable for =/> 72 hrs. - Current evidence of invasive fungal infection (blood or tissue culture); patients with recent fungal infection must have a subsequent negative cultures to be eligible; known HIV (new testing not required) or evidence of active hepatitis B or C infection (with rising transaminase values) - Hypersensitivity to cytarabine, daunorubicin or liposomal products - History of Wilson's disease or other copper-metabolism disorder Other exclusion criteria may apply. 3a88646513ff636dbd63388f7d14e81d 9514 Daily IL-2 for Steroid-Refractory Chronic Graft-versus-Host-Disease II Stephanie Lee, MD, MPH 2672.00 96 Chronic Graft Versus Host Disease (cGVHD) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.9514.html http://www.clinicaltrials.gov/ct/search?term=NCT01366092 NCT01366092 Chronic GVHD is a medical condition that may occur after a bone marrow, stem cell or cord blood transplant. The donor's immune system may recognize the your body (the host) as foreign and attempt to 'reject' it. This process is known as graft-versus-host-disease. It is thought that IL-2 may help control chronic GVHD by stopping the donor's immune system from 'rejecting' your body. In this research study, we are looking to see how IL-2 can be used in combination with steroids to treat cGVHD. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Recipient of allogeneic stem cell transplantation with myeloablative or non-myeloablative conditioning regimens - Steroid refractory cGVHD with systemic therapy onset within the prior 6 months - No more than 2 prior lines of cGVHD therapy - Estimated life expectancy > 3 months - Adequate organ function Other eligibility criteria may apply. - Ongoing prednisone requirement > 1 mg/kg/day (or equivalent) - Concurrent use of calcineurin-inhibitors plus sirolimus - History of thrombotic microangiopathy, hemolytic-uremic syndrome or thrombotic thrombocytopenic purpura - Active malignant relapse - Active uncontrolled infection - Uncontrolled cardiac angina or symptomatic congestive heart failure - Organ transplant (allograft) recipient - HIV-positive on combination antiretroviral therapy - Active hepatitis B or C - Pregnant or breast-feeding Other exclusion criteria may apply. b07cdaf023977e76d9060ffab679be8e 7623 Study of MDX-1105 in Subjects With Selected Advanced or Recurrent Solid Tumors (MDX1105-01) I Scott Tykodi, MD 7104 20; 28; 30; 34; 41; 46; 52; 65; 74; 83 Colon Cancer; Gastrointestinal Cancer; Genitourinary Cancer; Gynecological Cancer; Kidney Cancer; Lung Cancer; Melanoma; Ovarian Cancer; Renal Cancer; Solid Tumors Phase 1 Program, Study Line phase1@u.washington.edu 206/288-7551 http://www.fhcrc.org/en/treatment/clinical-trials/detail.7623.html http://www.clinicaltrials.gov/ct/search?term=NCT00729664 NCT00729664 Purpose The primary purpose of this study is to determine if MDX-1105 is safe and tolerated when administered every 14 days to subjects with selected advanced or recurrent solid tumors. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - ECOG PS 0 to 2 -