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, 16 May 2012 20:15:01 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 RATIONALE: Giving low doses of chemotherapy, such as fludarabine, and total-body irradiation (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. PURPOSE: This clinical trial studies giving fludarabine and total-body irradiation together followed by a donor stem cell transplant and cyclosporine and mycophenolate mofetil in treating HIV-positive patients with or without cancer Ages Eligible for Study: up to 64 Years Genders Eligible for Study: Both - Patients with hematologic malignancy, lymphoma or other HIV-associated malignancy are eligible provided these criteria are met: a) 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; b) HAART is initiated within one month of hematopoietic cell transplant; c) Viral load has decreased by >= 1.5 logs or viral load < 5000 copies/ml plasma on HAART therapy; d) CD4 count is allowed to be > 100 cells/ul - HIV infected patients without malignancy who have failed highly active antiretroviral therapy (HAART) are eligible provided that these criteria are met: q a) they have been treated with more than one regimen of HAART for a total of at least 6 months duration; b) the viral load is < 50 copies/ml plasma; c) 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 a) Peripheral blood stem cells will be collected from donors greater than 12 years of age; b) Bone marrow will be collected from donors less than 12 years of age - DONOR: HLA phenotypically identical unrelated donor; match grades allowed: a) Match grade 1: Matched at allele level for HLA-A, B, C, DRB1, and DQB1; b) 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. 338216f1324762de13fa80648c33e13d 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 Purpose RATIONALE: 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. 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. PURPOSE: 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 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) - 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 - 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%; ejection fraction is required if age > 50 years or there is a history of anthracycline exposure or history of cardiac disease - Carbon monoxide diffusing capacity (DLCO) < 30%, total lung capacity (TLC) < 30%, forced expiratory volume in one second (FEV1) < 30% and/or receiving supplementary continuous oxygen - 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. 4e1a63163de4090a9524b548af2e7669 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: o come back after first remission, or o did not respond to initial treatment, or o evolved from myelodysplastic or myeloproliferative syndrome. • MDS patients must have one of the following: o refractory anemia with excess blasts (RAEB), o RAEB in transformation (RAEBT), o refractory cytopenia with multilineage dysplasia (RCMD), o RCMD with ringed sideroblasts (RCMD-RS), or o 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. 8425330af110b52aea23d86b311ad018 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 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) 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 leukopheresis 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 leukopheresis; - c) Must have adequate veins for leukopheresis 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: - a) FHCRC matching allowed will be Grades 1.0 to 2.1; Unrelated donors who are prospectively: - i) Matched for 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 - 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 Fred Hutchinson Cancer Research Center (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. a5b3717556c220de82ecf1914f26ffa5 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 Purpose RATIONALE: Giving chemotherapy, such as temozolomide, carmustine (BCNU), 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 (G-CSF), 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. PURPOSE: This phase I/II trial is studying BCNU 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 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. 90fe4a3cef0f8b9826a72101126f9f89 6068 Melphalan and Amifostine Followed By One or Two Autologous or Syngeneic Stem Cell Transplants and Maintenance Therapy in Treating Patients With Stage II-III Multiple Myeloma III Bill Bensinger, MD 2004.00 36; 57 Hematologic Malignancies; Multiple Myeloma (MM) Kathy Lilleby, RN klilleby@fhcrc.org 206/667-5836 http://www.fhcrc.org/en/treatment/clinical-trials/detail.6068.html http://www.clinicaltrials.gov/ct/search?term=NCT00217438 NCT00217438 Purpose RATIONALE: Giving chemotherapy drugs, such as melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Chemoprotective drugs, such as amifostine, may protect normal cells from the side effects of chemotherapy. Giving chemotherapy with a peripheral stem cell transplant once or twice, using stem cells from the patient or an identical brother or sister, may allow more chemotherapy to be given so more cancer cells are killed. Giving maintenance therapy after a stem cell transplant may kill any cancer cells that remain. It is not yet known which dose of melphalan is more effective in treating multiple myeloma (MM). PURPOSE: This randomized phase III trial is studying two different doses of melphalan to compare how well they work when given together with amifostine followed by one or two autologous or syngeneic stem cell transplants and maintenance therapy in treating patients with stage II-III MM Ages Eligible for Study: 18 Years to 70 Years Genders Eligible for Study: Both - Patients who have MM undergoing autologous or syngeneic hematopoietic transplantation - Patients must meet Salmon and Durie criteria for initial diagnosis of MM - Transplant will be offered to patients with stage II or III MM - Measurable disease, defined as serum monoclonal protein >= 0.2 g/dl or Bence Jones protein >= 200 mg/24 h - Karnofsky >= 70 or Eastern Cooperative Oncology Group (ECOG) 0-2 - Life expectancy is not severely limited by concomitant illness - Left ventricular ejection fraction >= 50% - No uncontrolled arrhythmias or symptomatic cardiac disease - Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and diffusion capacity of carbon monoxide (DLCO) >= 50% - No symptomatic pulmonary disease - Human immunodeficiency virus (HIV) negative - Bilirubin < 2 mg/dl - Serum glutamic pyruvate transaminase (SGPT) < 2.5 x normal - Creatinine clearance >= 60 cc/min, estimated or measured - Signed informed consent Other eligibility criteria may apply. - Pregnant or lactating females - Uncontrolled infection - Planned tandem autologous/reduced intensity allograft - Insufficient PBSC for an autologous transplant (< 3.0 x 10^6 CD34+ cells/kg total) - Prior autologous transplant - Non-secretory myeloma and patients who are in a complete response or near complete response after conventional therapy - Patients unwilling to practice adequate forms of contraception if clinically indicated - Male patients on study need to be consulted to use latex condoms, even if they have had a vasectomy, every time they have sex with a woman who is able to have children - Patients with history of seizures - Patients receiving antihypertensive therapy that cannot be stopped for 24 hours preceding amifostine treatment Other exclusion criteria may apply. 2d88fa9d64a911b2cfd89b3eb9798e24 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 NCT00553098 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. e3c4d670d2c71c93d8fb6333ac06df15 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 11; 36; 61 Bone Marrow and Hematopoietic Stem Cell Transplant (BMT and HSCT); Hematologic Malignancies; 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 RATIONALE: 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 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. PURPOSE: This phase II trial is studying 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) 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) - 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 the Patient Care Conference (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. 2e33f0748919525079db4b714bf2c7cb 6788 Fludarabine Phosphate, Cyclophosphamide, and Total-Body Irradiation Followed by Donor Bone Marrow Transplant, Mycophenolate Mofetil, and Cyclosporine in Treating Patients With Fanconi Anemia I/II Hans-Peter Kiem, MD 2064.00 1; 2; 5; 11; 26; 36; 43; 61 Acute Lymphoid Leukemia (ALL); Acute Myeloid Leukemia (AML); Aplastic Anemia; Bone Marrow and Hematopoietic Stem Cell Transplant (BMT and HSCT); Fanconi Anemia; 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.6788.html http://www.clinicaltrials.gov/ct/search?term=NCT00453388 NCT00453388 RATIONALE: Giving low doses of chemotherapy, such as fludarabine phosphate and cyclophosphamide, and total-body irradiation (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. PURPOSE: This phase I/II trial is studying the side effects and best dose of TBI when given together with fludarabine phosphate and cyclophosphamide followed by donor bone marrow transplant, mycophenolate mofetil, and cyclosporine and to see how well they work in treating patients with Fanconi anemia (FA) - 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 < 8g/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 event and single-lineage BM failure as defined above - Any patient with FA and pre-existing cytogenetic abnormality including hematopoietic malignancy (acute myeloid leukemia [AML] or myelodysplastic syndrome [MDS]) in 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, HLA-haploidentical donors must be identical for one human leukocyte antigen (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 - 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) cardiac disease (ejection fraction < 35%) or lung disease - 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 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]) - 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. 351d0215f7a0edc3a65a9d77545bfd95 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 Stem Cell Transplantation Followed by Allogeneic Stem Cell Transplantation and Bortezomib Maintenance Therapy for 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 Purpose RATIONALE: 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. PURPOSE: 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). Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Meets Salmon/Durie criteria for initial diagnosis of MM - 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)-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 - 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 HLA phenotypically matched unrelated donor (according to Standard Practice HLA matching criteria, Grade #2.1): a) Matched for serologically recognized HLA-A, B, and C antigens and at least five of six HLA-A, B, and C alleles; b) Matched for HLA-DRB1 and DQB1 at the allele level (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) - Pregnancy - 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 - 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; ejection fraction is required if the patient has a history of anthracyclines or history of cardiac disease; b) Diffusing lung capacity for carbon monoxide (DLCO) < 50%, forced expiratory volume in 1 second (FEV) < 50% and/or receiving supplementary continuous oxygen; c) Liver function abnormalities: 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; d) Karnofsky score < 70% for adult patients - Patient with poorly controlled hypertension and on multiple antihypertensives - Patients with >= grade 2 peripheral neuropathy - 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 Fred Hutchinson Cancer Research Center (FHCRC) criteria for stem cell donation - DONOR: Age < 12 years - DONOR: A positive anti-donor cytotoxic crossmatch Other exclusion criteria may apply. 3ddca211f7e4de5ff358ac1e7af4fb52 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 7246 Nilotinib and Imatinib Mesylate After Donor Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia or Chronic Myelogenous Leukemia I/II Paul Carpenter, MD 2223.00 1; 19; 36; 43 Acute Lymphoid Leukemia (ALL); 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.7246.html http://www.clinicaltrials.gov/ct/search?term=NCT00702403 NCT00702403 Purpose RATIONALE: Nilotinib and imatinib mesylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase I/II trial is studying the side effects and best way to give nilotinib when given together with imatinib mesylate after donor stem cell transplant in treating patients with acute lymphoblastic leukemia or chronic myelogenous leukemia - Genders Eligible for Study: Both - Body surface area >= 1 m^2 - Allogeneic HCT - Acute lymphocytic leukemia (ALL) or chronic myelogenous leukemia (CML) characterized by the p190 and/or p210 BCR/ABL gene rearrangement - CML in accelerated phase, blast crisis, or blast crisis remission as defined by WHO criteria - CML in chronic phase if patient age =< 17 years or a patient of any age with CML in second chronic phase or beyond - Patients with minimal residual disease (MRD) that is not declining in response to tyrosine kinase inhibitor therapy must be screened for the T315I and other mutations - An appropriately matched related or unrelated donor - Signed informed consent - Patient must have a life expectancy of at least 2 months - Stated willingness of the patient to comply with study procedures and reporting requirements - Creatinine =< 2.0 x upper limit normal (ULN) - Platelets > 20 x 10^9 /L - Serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x ULN, conjugated bilirubin < 3 x ULN - Serum potassium phosphorus, magnesium, and calcium >= lower limit normal (LLN) or correctable with supplements prior to first dose of study drug; calcium levels may be corrected for hypoalbuminemia - Serum amylase and lipase < 1.5 x ULN - Female patients of childbearing potential must have negative pregnancy test within 7 days before initiation of study drug dosing; postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential; male and female patients of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug - Careful rationalization with a view to discontinuing or considering alternatives to any concomitant medications that have potential to prolong the QT interval Other eligibility criteria may apply. - Autologous transplant - Non-myeloablative transplant - Patient age > 17 years with CML in first chronic phase - Aberrant antigen expression on marrow leukemic blasts >= 5% by multidimensional flow cytometric assay immediately before conditioning (CML patients in chronic phase exempt from flow cytometry screening) - Ph+ ALL without complete cytogenetic remission immediately before conditioning - Known T315I mutation - Hypersensitivity to Gleevec or Tasigna - Patients who are Tasigna-resistant or intolerant - CNS involvement with leukemia at baseline (pre-imatinib therapy); CML CP, AP patients exempt from CNS involvement screening - Female patients who are pregnant, breast-feeding, or of childbearing potential without a negative serum pregnancy test at screening; male or female patients of childbearing potential unwilling to use effective contraceptive precautions throughout the trial; post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential - Life expectancy severely limited by diseases other than leukemia - Myocardial infarction within one year prior to starting nilotinib - Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, unstable angina) - Absolute neutrophil count (ANC) less than 1500 per microliter at study entry despite the use of filgrastim (G-CSF) - Impaired cardiac function, including any one of the following: - Complete left bundle branch block or bifascicular block (right bundle branch block plus left anterior hemiblock) or use of ventricular-paced pacemaker - Congenital long QT syndrome or a family history of long QT syndrome - History of or presence of significant ventricular or atrial tachyarrhythmias - Clinically significant resting bradycardia (< 50 beats per minute) - QTc > 450 milliseconds on screening electrocardiogram (ECG); if QTc > 450 and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient rescreened for QTc Other exclusion criteria may apply. 014c96a59ba6bb8b553007a735a576eb 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 Purpose This phase I/II trial is studying the side effects of laboratory-treated T cells when given with or without ipilimumab and 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 - Tumor expression of NY-ESO-1 (2+ staining or > 25%) by immunohistochemistry (IHC) - 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 - 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, immunotherapy, radiotherapy or major surgery; at least 6 weeks for nitrosoureas, mitomycin C, and liposomal doxorubicin - 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 - Willing and able to give informed consent 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 - WBC < 2000/uL - 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 FEV1 < 2.0 L or DLco (corr for Hgb) < 75% will be excluded - Significant cardiovascular abnormalities as defined by any one of the following: - Congestive heart failure - Clinically significant hypotension - Symptoms of coronary artery disease - Presence of cardiac arrhythmias on electrocardiogram (EKG) requiring drug therapy - 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 - The following agents are not allowed while on study: systemic corticosteroids (except as outlined for management of transferred T cell toxicity), immunotherapy (for example, interleukins, interferons, melanoma vaccines, intravenous immunoglobulin, expanded polyclonal TIL or LAK therapy), pentoxifylline, other investigational agents Other exclusion criteria may apply. 2dedfcef499554f9534a792701cf1c19 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 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.7570.html http://www.clinicaltrials.gov/ct/search?term=NCT00867529 NCT00867529 RATIONALE: 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. PURPOSE: This phase II trial is studying rituximab in treating patients undergoing donor peripheral blood stem cell transplant for relapsed or refractory B-cell lymphoma 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 - Able to give informed consent (if >= 18 years of age), or with a legal guardian capable of giving consent (if < 18 years of age) - Patients with an appropriate related or unrelated donor; human leukocyte antigen (HLA)-haploidentical donors are excluded Other eligibility criteria may apply. - Ineligible for non-myeloablative allogeneic HCT - Receiving an HLA-haploidentical allograft - Females who are pregnant or breast-feeding - Are fertile but unwilling to use contraception during and for at least 12 months after HCT Other exclusion criteria may apply. d222c5ef23d7ad2cfeddc4b16b275871 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 RATIONALE: 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. Monoclonal antibodies, such as gemtuzumab ozogamicin, 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 azacitidine together with gemtuzumab ozogamicin may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving azacitidine together with gemtuzumab ozogamicin works in treating patients relapsed myelodysplastic syndrome, chronic myelomonocytic leukemia, or acute myeloid leukemia who have undergone stem cell transplant. Genders Eligible for Study: Both - MDS, CMML or AML patients (as diagnosed by 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 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 - 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 IWG criterial - Evidence of CNS disease at time of relapse by morphology or flow (a diagnostic LP is not required at time of relapse) - Serum Creatinine > 2 x ULN (upper limit of normal) - AST/ALT > 2x ULN - Performance status > 2 (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. b2b7f3761bc3be22606ac64dc1ae11ab 7549 Bortezomib and Vorinostat in Treating Patients With Multiple Myeloma Who Have Undergone Autologous Stem Cell Transplant II Leona Holmberg, MD, PhD 2253.00 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.7549.html http://www.clinicaltrials.gov/ct/search?term=NCT00839956 NCT00839956 RATIONALE: Bortezomib and vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving bortezomib together with vorinostat after an autologous stem cell transplant may stop the growth of any cancer cells that remain after transplant. PURPOSE: This phase II trial is studying the side effects of giving bortezomib together with vorinostat and to see how well it works in treating patients with multiple myeloma who have undergone autologous stem cell transplant Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Any autologous patient who underwent high dose melphalan (>= 140 mg/m^2) therapy or peripheral blood stem cell (PBSC) rescue for any stage of multiple myeloma and did not participate in another clinical transplant trial whose primary endpoint is also evaluating long-term, disease-free survival, or survival - Platelet count (transfusion independent) > 75,000 cells/mm^3 and absolute granulocyte count > 1500 cells/mm^3 for 5 calendar days after recovery from high dose therapy - Consenting for study between 30 days to 120 days after transplant - Female patient of childbearing potential has a negative serum pregnancy test beta-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 treatment on study, starting with visit 1 and for 3 months afterward - Male patient agrees to use an adequate method of contraception for the duration of the treatment on study and for 3 months afterward Other eligibility criteria may apply. - Eastern Cooperative Oncology Group (ECOG) performance status >= 2 - A left ventricular ejection fraction less than 45% pre-transplant - Congestive heart disease with transplant, history of MI, history of coronary artery disease, or prolonged QTC - Total bilirubin greater than 2 mg/ml (unless history of Gilbert's disease) - Aspartate aminotransferase (SGOT) or alanine aminotransferase (SGPT) > 2.5 x upper limit of normal - Creatinine clearance < 20 ml/minute, calculated by Cockroft-Gault formula or measured urine - Cannot give informed consent - Untreated systemic infection - Poorly-controlled diabetes mellitus (DM) >= grade 3 peripheral neuropathy - Prior history of human immunodeficiency virus (HIV) positivity with pre-transplant evaluation 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 - Potassium (K) and magnesium (Mg) < normal limits - Patient who has had chemotherapy, radiotherapy, or biological therapy, within 30 days (42 days for nitrosoureas or mitomycin C) prior to initial dosing with study drug(s) 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 device within 30 days of initial dosing with study drugs - Patient had prior treatment with an histone deacetylase inhibitor (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 - 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 is pregnant or breast-feeding, or expecting to conceive or father children within the projected duration of the study - 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 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 Other exclusion criteria may apply. bde05e91f81f9d49f4edd349a19a356e 7645 Treosulfan and Fludarabine Before Donor Stem Cell Transplant in Treating Patients With Nonmalignant Inherited Disorders II Lauri Burroughs, MD 2256.00 127 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 RATIONALE: 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 potentially res for patients and pot. Investigators at the Fred Hutchinson Cancer Research Center in collaboration with Oregon Health & Sciences 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. PURPOSE: 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 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 PI (Dr. Lauri Burroughs) and potentially the nonmalignant board to determine if they are eligible for HCT on this study - DONOR: 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 DNA typing - DONOR: Bone marrow is the preferred cell source; PBSC are allowed if donor refuses or is unable to give marrow Other eligibility criteria may apply. - Patients with aplastic anemia and Fanconi anemia - 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 DLCO < 60% of predicted (or, if unable to perform pulmonary function tests, then 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. 39989f8d7e248da58ac1faff097ab414 7599 Treosulfan, Fludarabine Phosphate, and Total-Body Irradiation Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia or Myelodysplastic Syndrome II Boglarka Gyurkocza, MD 2272.00 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.7599.html http://www.clinicaltrials.gov/ct/search?term=NCT00860574 NCT00860574 The purpose of this study is to look at the effects, good or bad, of an experimental combination of low-dose total body irradiation (TBI) and chemotherapy drugs, given prior to stem-cell transplantation, in patients with high-risk acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). The chemotherapy drugs used in this research study are treosulfan and fludarabine. These drugs will be given along with low-dose total body irradiation (TBI). Study participants will then undergo a donor bone-marrow or peripheral-blood stem-cell transplant. Participants will receive treatment at the Seattle Cancer Care Alliance (SCCA) and at the University of Washington Medical Center (UWMC). Treatment on this study will last about 3 ½ months. We would like to do long-term follow-up by calling each study participant on the telephone once a year to see how he or she is doing. 1. Age 60 years or younger 2. Diagnosed with one of the following: - Acute myeloid leukemia (AML) beyond 1st remission, or intermediate or high-risk AML in 1st complete remission - Myelodysplastic syndrome (MDS) 3. A suitable donor is available Other eligibility criteria may apply. • Prior or concurrent umbilical cord blood transplantation (prior autologous or allogeneic hematopoietic stem cell transplantation is allowed) • Inadequate organ function (heart, lung, kidney, liver) • Active infectious disease, HIV-positivity, or active infectious hepatitis • CNS leukemic involvement • Pregnant or lactating Other exclusion criteria may apply. b2df1ff5168e36a953ef64cf08529efe 7628 Vorinostat, Gemtuzumab Ozogamicin, and Azacitidine in Treating Older Patients With Relapsed or Refractory Acute Myeloid Leukemia I/II Roland Walter, MD 2288.00 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.7628.html http://www.clinicaltrials.gov/ct/search?term=NCT00895934 NCT00895934 RATIONALE: Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as gemtuzumab ozogamicin, 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. 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. Giving vorinostat together with gemtuzumab ozogamicin and azacitidine may kill more cancer cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of vorinostat and to see how well it works when given together with gemtuzumab ozogamicin and azacitidine in treating older patients with relapsed or refractory acute myeloid leukemia (AML). Ages Eligible for Study: 50 Years and older Genders Eligible for Study: Both DISEASE CHARACTERISTICS: Morphological diagnosis of acute myeloid leukemia (AML) - No acute promyelocytic leukemia (FAB M3) - Biphenotypic AML allowed Must have cytogenetic analysis performed on bone marrow specimen within 14 days prior to study entry unless undergoing cytoreduction with hydroxyurea for WBC = 25,000/µL Requires first salvage chemotherapy for persistent or relapsing disease after = 1 course of conventional chemotherapy (e.g., with "7+3"), as defined by persistence of = 50% myeloid blasts measured on 1 occasion or persistence of = 20% myeloid blasts measured on 2 occasions with no improvement between first and second assessments performed 3-7 days apart - Duration of first complete remission < 12 months OR primary resistant disease - Not in remission - No second or subsequent relapse No refractory/relapsing chronic myelogenous leukemia in blast crisis No clinical evidence suggestive of CNS involvement with leukemia unless a lumbar puncture confirms the absence of leukemic blasts in the cerebrospinal fluid PATIENT CHARACTERISTICS: ECOG/WHO/Zubrod performance status 0-3 WBC < 25,000/µL - Patients with WBC = 25,000/µL must undergo cytoreduction with hydroxyurea prior to study enrollment - Patients with symptoms/signs of hyperleukocytosis or WBC > 100,000/µL may undergo leukapheresis prior to study enrollment Bilirubin = 1.5 times upper limit of normal (ULN) (unless elevation is thought to be due to hepatic infiltration by AML, Gilbert syndrome, or hemolysis) AST and ALT = 1.5 times ULN (unless elevation is thought to be due to hepatic infiltration by AML) Serum creatinine = 1.5 times ULN LVEF = 40% by MUGA scan, echocardiography, or other appropriate diagnostic study Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for = 3 months after completion of study treatment HIV positivity allowed provided CD4 count = 200 cells/µL and there are no active AIDS-related complications No clinical evidence of congestive heart failure No other malignancy unless the patient was diagnosed = 2 years ago AND has been disease-free for = 6 months after completion of curative intent therapy - Patients with treated nonmelanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia are eligible, regardless of disease-free duration, provided definitive treatment for the condition has been completed - Patients with organ-confined prostate cancer are eligible provided there is no evidence of recurrent or progressive disease, based on prostate-specific antigen (PSA) values, AND hormonal therapy has been initiated or a radical prostatectomy has been performed No known hypersensitivity to gemtuzumab ozogamicin, vorinostat, azacitidine, or mannitol No uncontrolled systemic fungal, bacterial, viral, or other infection, defined as exhibiting ongoing signs/symptoms related to the infection with no improvement despite appropriate antibiotics or other treatment PRIOR CONCURRENT THERAPY: See Disease Characteristics Recovered from all prior therapy Prior autologous or allogeneic hematopoietic stem cell transplant allowed provided relapse occurred 6-12 months after transplant At least 14 days since prior active therapy for AML, except for hydroxyurea At least 6 months since prior and no concurrent chemotherapy or radiotherapy for another malignancy - Concurrent hormonal therapy allowed No prior gemtuzumab ozogamicin, histone deacetylase (HDAC) inhibitors (including valproic acid for control of seizure activity or for other purposes), or demethylating agents for treatment of AML No other concurrent investigational therapy or anticancer therapy No concurrent medications that may cause torsades de pointes Other eligibility criteria may apply. Other exclusion criteria may apply. 8a027a91494babdd2f6ad0a5758aa296 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 RATIONALE: 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 autologous stem cell transplant may thus kill any lymphoma cells that remain after transplant. PURPOSE: This phase II trial is studying the side effects and how well bortezomib and vorinostat work in treating patients with non-Hodgkin lymphoma after an autologous stem cell transplant. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both Inclusion Criteria for Transplant: - Diagnosis of non-Hodgkin's lymphoma, transformed B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, diffuse large B-cell or T-cell lymphoma, and deemed a candidate for autologous transplant - Signed informed consent - Male patient agrees to use an adequate method of contraception for the duration of the study - Renal: Creatinine clearance (calculated creatinine clearance is permitted) > 40 mL/min - Pulmonary: DLCO, FEV1, and FVC >= 50% of predicted (corrected for hemoglobin) - Hepatic: Bilirubin =< 2.0 mg/dL (except for isolated hyperbilirubinemia attributed to Gilbert syndrome) and ALT and AST =< 3x the upper limit of normal - 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, patients > 60 years of age must have a left ventricular ejection fraction of at least >= 40% demonstrated by MUGA or Echo - Autologous graft with a minimum of >= 3.0 x 10^6 CD34+ cells/kg (not CD34 selected) - Female patients of childbearing potential has a negative serum pregnancy test beta-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 Inclusion Criteria for Maintenance Therapy: - 30-120 days post ASCT for non-Hodgkin's lymphoma: CrCL >= 40 mL/min; PLT >= 75,000, and ANC >= 1500 cells/mm3 for 5 days after recovery from ASCT nadir; TB =< 2.0 (unless history of Gilbert's disease), 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 HSCT - Patients with evidence of MDS/AML or abnormal cytogenetics analysis indicative of MDS on the pre-transplant bone marrow examination - Prolonged QTC on EKG - Poorly-controlled DM - Prior history of 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) - History of CNS disease - Patient had prior treatment with an 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 - 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 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 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: - MI with ASCT or developed dilated cardiomyopathy with ASCT - Untreated systemic infection - K and Mg < normal limits of adequate supplementation - >= grade 2 peripheral neuropathy within 14 days before beginning maintenance therapy - Any other non-study investigational agent; radiation therapy will not be allowed - Prolonged QTC - Poorly controlled DM Other exclusion criteria may apply. c4f75a9a044f73e25260c659a1d1bdef 7555 Clofarabine and Cytarabine in Treating Older Patients With Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndromes That Have Relapsed or Not Responded to Treatment I/II John Pagel, MD, PhD 2302.00 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.7555.html http://www.clinicaltrials.gov/ct/search?term=NCT00839982 NCT00839982 RATIONALE: Drugs used in chemotherapy, such as clofarabine and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving clofarabine together with cytarabine may kill more cancer cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of clofarabine when given together with cytarabine and to see how well they work in treating older patients with acute myeloid leukemia or high-risk myelodysplastic syndromes that have relapsed or not responded to treatment Ages Eligible for Study: 60 Years and older Genders Eligible for Study: Both - Diagnosis of 1st relapse or refractory AML; or patients with high risk MDS (10-19% blasts) who have received previous therapy 1st remission must have been < 1 year - Must not have received previous ara-C or clofarabine - ECOG Performance Status of 0 - 2 - Not candidates for standard 7 + 3 regimen (Ara-C and an anthracycline), high dose Ara-C, or hematopoietic stem-cell transplantation - Serum creatinine =< 1.0 mg/dL; if serum creatinine >1.0 mg/dL, then the estimated glomerular filtration rate (GFR) must be >50 L/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease equation - Serum bilirubin =< 1.5 x upper limit of normal (ULN) - Aspartate transaminase (AST)/alanine transaminase (ALT) =< 2.5 x ULN - Alkaline phosphatase =< 2.5 x ULN - Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent - Female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment - Male and female patients should use an effective contraceptive method during the study and for a minimum of 6 months after study treatment Other eligibility criteria may apply. - Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol - Patients with acute promyelocytic leukemia (APL) - Use of investigational agents within 30 days or any anticancer therapy within 2 weeks before study entry with the exception of hydroxyurea; the patient must have recovered from all acute toxicities from any previous therapy - 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 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 - Have had a diagnosis of another malignancy, unless the patient has been disease free for at least 3 years following the completion of curative intent therapy including the following: - Patients with treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, regardless of the disease-free duration, are eligible for this study if definitive treatment for the condition has been completed - Patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen (PSA) values are also eligible for this study if hormonal therapy has been initiated, or a radical prostatectomy or definitive radiotherapy has been performed - Have currently active gastrointestinal disease, or prior surgery that may affect the ability of the patient to absorb oral clofarabine Other exclusion criteria may apply. 25890e5ea3c41d3f9a1326211bc57599 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 RATIONALE: Giving chemotherapy drugs, such as fludarabine phosphate, and total-body irradiation (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. PURPOSE: This phase I trial uses pretargeted radioimmunotherapy and donor peripheral blood stem cell transplant employing fludarabine phosphate and TBI to treat patients with high-risk acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Patients must have an expected survival of > 60 days and must be free of active infection - Karnofsky score >= 70 or ECOG =< 2 - 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 must have an HLA-identical sibling donor or an HLA-matched unrelated donor who meets standard Seattle Cancer Care Alliance (SCCA) and/or NMDP criteria for PBSC donation - Related donors should be matched by molecular methods at the intermediate resolution level at HLA-A, B, C, and DRB1 according to 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 - 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/mm3 (control with hydroxyurea or similar agent is allowed) - Patients must have normal hepatic function (bilirubin, AST and ALT < 2 times the upper limit of normal) - Patients must have a creatinine clearance greater than 50/mL per minute (test must be performed within 28 days prior to registration) 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: left ventricular ejection fraction <35%; corrected DLCO <35% and/or receiving supplemental continuous oxygen - 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 HIV - Perceived inability to tolerate diagnostic or therapeutic procedures, particularly treatment in radiation isolation - 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 - Liver abnormalities: fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, or hepatic encephalopathy - Women of childbearing potential who are pregnant (beta HCG +) or breast feeding - Active CNS leukemia Other exclusion criteria may apply. 322755b33f0f6feb20894a52ba1fe476 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 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.8047.html http://www.clinicaltrials.gov/ct/search?term=NCT01097057 NCT01097057 RATIONALE: 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. PURPOSE: 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. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - 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 - Cardiac: left ventricular ejection fraction at rest >= 50% demonstrated by MUGA or echocardiogram - Renal: creatinine clearance (calculated creatinine clearance is permitted) > 50 mL/min - Signed informed consent - Planned autologous transplant within 3 months after collection of PBSCs - Diagnosis of CD20+ non-Hodgkin's lymphoma Other eligibility criteria may apply. - HIV positive - 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 or women unwilling to use contraceptive techniques from the time of chemo-mobilization - Prior autologous or allogeneic HSCT - Plan to be treated on another investigational therapy within 4 weeks of enrolling on this study - Hepatitis B carriers - 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 - Other investigational agents during study participation Other exclusion criteria may apply. e98aa3fe810e9a4531514640d24f64c4 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 7862 High-dose Chemotherapy for Poor-prognosis Relapsed Germ-Cell Tumors II Leona Holmberg, MD, PhD 2328.00 83; 133 Solid Tumors; Germ Cell Tumors (GCT) Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.7862.html http://www.clinicaltrials.gov/ct/search?term=NCT00936936 NCT00936936 Purpose: The goal of this clinical research study is to learn if bevacizumab, when given in combination with 2 cycles of high-dose chemotherapy, can help to control germ-cell tumors. The first cycle of chemotherapy will include the drugs gemcitabine, docetaxel, melphalan, and carboplatin. The second cycle of chemotherapy will include the drugs ifosfamide, carboplatin, and etoposide. The safety of these drug combinations will also be studied. Ages Eligible for Study: 18 Years to 65 Years Genders Eligible for Study: Both - Patients with seminomatous or nonseminomatous germ-cell tumors (GCT) in one of the following groups: A) First relapse or progression or second response with an intermediate or high risk according to the Beyer model. B) Second relapse or beyond. - Adequate renal glomerular and tubular function, as defined by estimated serum creatinine clearance >/=50 ml/min and/or serum creatinine </= 1.8 mg/dL, and urinary protein excretion </=500 mg/day. - Adequate hepatic function, as defined by ALT and AST </=3 x upper limit of normal (ULN); serum bilirubin and alkaline phosphatase </=2 x ULN or considered not clinically significant. - Adequate pulmonary function with FEV1 (Forced expiratory volume in the first second), FVC (Forced vital capacity) and DLCO (diffusing capacity of the lung for carbon monoxide) >/=50% of predicted, corrected for volume and hemoglobin. - Adequate cardiac function with LVEF (left ventricular ejection fraction) >/=40%. No uncontrolled arrhythmias or symptomatic cardiac disease. - Zubrod performance status 0-2. - A minimum apheresis collection of 5 million CD34+ cells/kg of autologous hematopoietic progenitor cells (AHPC). - Written informed consent by patients and/ or their parents or legal guardians. Assent for those patients inclusive of ages 12 to 17. Other eligibility criteria may apply. - Growing teratoma syndrome, defined as enlarging tumor masses with normal serum markers during chemotherapy for nonseminomatous GCT. - Late tumor relapses, defined as those occurring > 3 years after completion of first-line chemotherapy - Major surgery within 30 days before the initiation of study treatment - Radiotherapy within 21 days prior to initiation of study treatment - Patients with active central nervous system (CNS) disease, defined as brain or meningeal metastases that are not in complete remission. - Patients with active hepatitis B, either active carrier (HBsAg +) or viremic (HBV DNA >/=10,000 copies/mL, or >/= 2,000 IU/mL). - Evidence of either cirrhosis or stage 3-4 liver fibrosis in patients who either show chronic hepatitis C or positive hepatitis C serology. - Active infection requiring parenteral antibiotics. - HIV infection, unless the patient is receiving effective antiretroviral therapy with undetectable viral load and normal CD4 counts - Patients who have had a previous autologous or allogeneic stem cell transplant in the previous 12 months. - Bleeding diathesis - Hypercoagulable state or thrombophilia - Aspirin (>325 mg/day) use within 10 days before initiation of study treatment. - Ongoing uncontrolled hypertension (>140/90 mm Hg on medication). - Non-healing wound or significant traumatic injury within 30 days before the initiation of study treatment - Positive pregnancy test in a female patient of childbearing potential defined as not post menopausal for twelve months or no previous surgical sterilization. Other exclusion criteria may apply. 60cf347690e0cceb1de64c1c63d198a3 7875 Clofarabine, Cytarabine, and Filgrastim Followed by Infusion of Non-human Leukocyte Antigen (HLA) Matched Ex Vivo Expanded Cord Blood Progenitors in Treating Patients With Acute Myeloid Leukemia I Colleen Delaney, MD, MSc 2335.00 2; 36; 43; 121 Acute Myeloid Leukemia (AML); Hematologic Malignancies; Leukemia; 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.7875.html http://www.clinicaltrials.gov/ct/search?term=NCT01031368 NCT01031368 The purpose of this research study is to determine the safety and efficacy of an experimental treatment for patients with acute myeloid leukemia. Participants in this study will receive an infusion of cord-blood progenitor cells after receiving a course of chemotherapy that includes the drugs clofarabine and cytarabine. Patients will also receive granulocyte-colony stimulating factor. The cord-blood infusion may be followed by up to 3 more courses of chemotherapy. Hematopoietic progenitor cells are cells that give rise to the blood system. The cord-blood progenitor cells will be grown or "expanded" in a laboratory before the infusion takes place. The cord-blood progenitor cells will not be genetically matched with the participant’s tissue type. This study is being done to determine whether or not giving these expanded cells after chemotherapy is safe and helps the blood system to recover more quickly from chemotherapy. Cytarabine is approved by the Food and Drug Administration (FDA) for use in AML. Clofarabine is approved for use in some pediatric patients with another type of leukemia, called acute lymphoblastic leukemia (ALL). Participants will receive treatment at the Seattle Cancer Care Alliance (SCCA) and University of Washington Medical Center (UWMC). The study includes up to 6 months of study treatment for participants who receive all 4 courses of chemotherapy. After that, we would like to maintain follow-up contact for a total of 5 years on study. • 18-70 years of age • Diagnosed with one of the following: - Acute myeloid leukemia (by WHO criteria), either relapsed or refractory - Untreated AML patients with cytogenetic or molecular abnormalities associated with poor prognosis - Untreated AML patients with intermediate prognosis Other eligibility criteria may apply. • Allogeneic transplant recipients • Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol • Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver (including symptomatic hepatitis, veno-occlusive disease), or other organ system dysfunction • 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 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. 906e8541e15618ae781103ca99a28718 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 Purpose 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 the 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 12 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 > 70% 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 transaminase (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 Other exclusion criteria may apply. b31379c99aeced98b7130c2bf4250056 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 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.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 after HCT within 3 months of study enrollment - The baseline absolute FEV1 must be >= 10% lower than the pre-transplant FEV1 as defined by the pre-transplant FEV1 minus the baseline FEV1 - Life expectancy > 6 months at the time of enrollment as judged by the enrolling investigator - All females of childbearing potential must have a negative serum or urine pregnancy test =< 7 days before study drug administration - Subject (or parent/guardian) has the ability to understand and willingness to sign a written consent document Other eligibility criteria may apply. - Patients with recurrent malignancy or disease progression requiring anticancer therapy - Known history of allergy to montelukast, zafirlukast, azithromycin, erythromycin, or clarithromycin - Pregnant females or nursing mothers - Transaminases > 5 X upper limit of normal (ULN) - Total bilirubin > 3 X ULN - Patients currently on daily inhaled steroid (with any inhaled steroid equivalent to fluticasone) for > 1 month preceding enrollment - Patients currently on montelukast for > 1 month preceding enrollment - Patients currently on chronic dosing of azithromycin (>= 3 x/week) for > 1 month preceding enrollment; patients that have taken a Z-pak or other macrolides to treat infection are eligible - Patients requiring > 1.2 mg/kg/day of prednisone (or equivalent steroid) - Receipt of any non-Food and Drug Administration (FDA) approved study medication within the last 4 weeks (this does not apply to use of FDA-approved drugs for an off-label indication) - Evidence of any viral, bacterial or fungal infection not responding to appropriate treatment - Patients with clinical asthma (variable and recurring symptoms of airflow obstruction and bronchial hyper-responsiveness) - 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 on long-term oxygen therapy - Patients with uncontrolled substance abuse or psychiatric disorder - Patients who are deemed (by the local principal investigator [PI] or the pulmonary function test [PFT] lab) unable to reliably perform pulmonary function tests Other exclusion criteria may apply. 7ee45c9789e048247167297b976eec6e 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 - 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 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 - Patients must have evidence of persistent lymphoma by physical examination, radiographic studies, blood or bone marrow evaluation, flow cytometry, or polymerase chain reaction (PCR) - 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 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 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 In-ibritumomab tiuxetan dose) Other exclusion criteria may apply. f4dbd0d47236f88d92f42ed85185b3db 8665 Cyclosporine, Pravastatin Sodium, Etoposide, and Mitoxantrone Hydrochloride in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia I/II Roland Walter, MD 2409.00 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.8665.html http://www.clinicaltrials.gov/ct/search?term=NCT01342887 NCT01342887 Purpose This phase I/II trial studies the side effects and best dose of etoposide and mitoxantrone hydrochloride when given together with cyclosporine and pravastatin sodium and to see how well they work in treating patients with relapsed or refractory acute myeloid leukemia (AML). Cyclosporine may inhibit efflux of cancer drugs out of cancer cells and may thereby improve chemotherapy treatment for AML. Pravastatin sodium may stop the growth of cancer cells by blocking some of the nutrients needed for cell growth. Drugs used in chemotherapy, such as etoposide and mitoxantrone hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving cyclosporine together with pravastatin sodium, etoposide, and mitoxantrone hydrochloride may kill more cancer cells Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Treatment-related mortality (TRM) score < 22.8 as calculated with simplified model - Prior morphological diagnosis of AML according to the 2008 World Health Organization (WHO) diagnostic criteria; patients with biphenotypic AML are eligible; patients with acute promyelocytic leukemia with t(15;17)(q22;q12) and variants are ineligible - Relapsed/persistent disease as defined by International Working Group criteria; 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 - Eastern Cooperative Oncology Group (ECOG) performance status of 0-3, assessed at time of registration - Should be off any active therapy for AML with the exception of hydroxyurea or low-dose cytarabine (=< 100 mg/m^2) for at least 14 days prior to study registration unless patient has rapidly progressive disease, and all Grade 2-4 non-hematologic toxicities must have resolved - 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 glutamic pyruvate transaminase (SGPT) (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 scan (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 - Patients with symptoms/signs of hyperleukocytosis or white blood cell (WBC) > 100,000/uL can be treated with leukapheresis prior to enrollment - 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 - Ability to understand and the willingness to sign a written informed consent document; the consent can be obtained from a legally authorized representative if the patient is unable to provide informed consent Other eligibility criteria may apply. - Diagnosis of another malignancy, unless the patient was diagnosed at least 2 years earlier and has been disease-free for at least 6 months following the completion of curative intent therapy with the following exceptions: - Patients with treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, regardless of the disease-free duration, are eligible for this study if definitive treatment for the condition has been completed - Patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen (PSA) values are also eligible for this study if hormonal therapy has been initiated or a radical prostatectomy has been performed - Refractory/relapsing blast crisis of chronic myelogenous leukemia (CML) - Known hypersensitivity to any study drug - Human immunodeficiency virus (HIV)-positive patients are excluded if their cluster of differentiation (CD)4 count is below 200 cells/uL or if they have active acquired immune deficiency syndrome (AIDS)-related complications, as these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy - Pregnant or lactating patients; women of child-bearing potential must undergo pregnancy test within 7 days prior to registration - Uncontrolled systemic fungal, bacterial, viral, or other infection (defined as exhibiting progressive signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment) - Patients may not be receiving any other investigational agents Other exclusion criteria may apply. b9592c3635e0e1bdedb64c00dd0a8335 8330 Panobinostat (LBH589) and Imatinib Mesylate in Treating Patients With Previously Treated Chronic Phase Chronic Myelogenous Leukemia I Vivian Oehler, MD 2412.00 19; 36; 43 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.8330.html http://www.clinicaltrials.gov/ct/search?term=NCT00686218 NCT00686218 RATIONALE: Panobinostat and imatinib mesylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase I trial is studying the side effects and best dose of panobinostat when given together with imatinib in treating patients with previously treated chronic phase chronic myelogenous leukemia. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed - CML CP patients who have been treated with and tolerated Imatinib for 1 year or more, have achieved at least major cytogenetic response and continue to be BCR-ABL positive (Patients should be receiving Imatinib at a dose of 400 daily at the time of entry into the study) - ANC and PLT need to be in the normal range - Serum albumin >= 3g/dL - AST/SGOT and ALT/SGPT =< 2.5 x upper limit of normal (ULN) - Serum bilirubin =< 1.5 x ULN - Serum creatinine =< 1.5 x ULN or 24-hour creatinine clearance >= 50 ml/min - Serum potassium >= lower limit of normal (LLN) - Serum phosphorus >= LLN - Serum total calcium (corrected for serum albumin) or serum ionized calcium >= LLN - Serum magnesium >= LLN - ECOG performance status of =< 2 Other eligibility criteria may apply. - Prior treatment with an HDAC inhibitor - Patient who have been treated with Imatinib < 1 year or patients are currently being treated with Imatinib at a dose > 400 mg daily - Impaired cardiac function including any one of the following: Screening ECG with a QTc > 450 msec; Patients with congenital long QT syndrome; History or presence of sustained ventricular tachycardia; Any history of ventricular fibrillation or torsades de pointes; Bradycardia defined as heart rate < 50 beats per minute (patients with a pacemaker and heart rate >= 50 beats per minute are eligible); Patients with a myocardial infarction or unstable angina within 6 months of study entry; Congestive heart failure (NY Heart Association class III or IV); Right bundle branch block and left anterior hemiblock (bifascicular block) - Uncontrolled hypertension - Concomitant use of drugs with a risk of prolonging the QT interval or inducing torsades de pointes - Concomitant use of CYP3A4 inhibitors - Patients with unresolved diarrhea > CTCAE grade 1 - Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LBH589 - Other concurrent severe and/or uncontrolled medical conditions - Patients who have received chemotherapy, any investigational drug or undergone major surgery < 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy - Concomitant use of any other anti-cancer therapy or radiation therapy - Patients being treated with Coumadin (unless patients who require anticoagulation can be switched to a low-molecular weight or standard heparin) - Female patients who are pregnant or breast feeding or patients of reproductive potential not willing to use a double method of contraception including a barrier method (i.e. condom) during the study and 3 months after the end of treatment (Women of childbearing potential [WOCBP] must have a negative serum pregnancy test within 7 days of the first administration of oral LBH589) - Male patients whose sexual partners are WOCBP not willing to use a double method of contraception including condom during the study and 3 months after the end of treatment - Patients with a history of another primary malignancy within 5 years other than curatively treated CIS of the cervix, or basal or squamous cell carcinoma of the skin - Patients with known positivity for human immunodeficiency virus (HIV) or hepatitis C; baseline testing for HIV and hepatitis C is not required - Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent Other exclusion criteria may apply. 5365cf18cd69f5f7531bc59aa12d9589 8291 Bendamustine Hydrochloride and Idarubicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia or Myelodysplastic Syndrome I/II John Pagel, MD, PhD 2413.00 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.8291.html http://www.clinicaltrials.gov/ct/search?term=NCT01141725 NCT01141725 Purpose RATIONALE: Drugs used in chemotherapy, such as bendamustine hydrochloride or idarubicin, 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. PURPOSE: This phase I/II trial is studying the side effects and best dose of bendamustine hydrochloride when given together with idarubicin in treating older patients with previously untreated acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) Ages Eligible for Study: 50 Years and older Genders Eligible for Study: Both - Diagnosis of untreated AML or MDS with 10-19% marrow blasts; patients may be enrolled if they received prior treatment with demethylating agents specifically for the purpose of treating MDS - 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 x upper limit of normal (ULN) - Aspartate transaminase (AST)/alanine transaminase (ALT) =< 2.5 x ULN - Alkaline phosphatase =< 2.5 x ULN - Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent - 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 Other eligibility criteria may apply. - Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol - Use of investigational agents within 30 days or any anticancer therapy within 2 weeks before study entry with the exception of hydroxyurea; subjects who are enrolled with high risk MDS (specifically) may have prior treatment with drugs in the class called "demethylating agents"; examples of these drugs include 5-azacytidine (azacitidine) and 5-azadeoxycytidine (decitabine), and may include approved or experimental drugs not currently used, which fall into this class and may be developed in the future; the patient must have recovered from all acute toxicities from any previous therapy - 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 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 - Known hypersensitivity to bendamustine (bendamustine hydrochloride) or idarubicin - 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) - Have had a diagnosis of another malignancy, unless the patient has been disease-free for at least 3 years following the completion of curative intent therapy - Other circumstances in which patients with prior malignancies are not excluded, include the following: - Patients with treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, regardless of the disease-free duration, if definitive treatment for the condition has been completed - Patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen (PSA) values if hormonal therapy has been initiated, or a radical prostatectomy or definitive radiotherapy has been performed - Concurrent hormonal therapy is allowed Other exclusion criteria may apply. 6ac1ff73d91dac9840c007f3326d9458 8352 Phase 1 Nilotinib in Steroid Dependent/Refractory Chronic Graft Versus Host Disease I Paul Carpenter, MD 2423.00 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.8352.html http://www.clinicaltrials.gov/ct/search?term=NCT01155817 NCT01155817 PRIMARY OBJECTIVES: Determine the safety and tolerability of nilotinib in steroid dependent / refractory cGVHD. SECONDARY OBJECTIVES: Determine the clinical efficacy of nilotinib in steroid dependent / refractory cGVHD. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both Inclusion Criteria:5.1.1 Steroid dependent/refractory cGVHD defined as: 1. Dependent disease - Persistent cGVHD manifestations requiring a glucocorticoid dose >= prednisone 0.25 mg/kg/day (0.5 mg/kg po qod) for at least 12 weeks. 2. Refractory disease - Progressive cGVHD manifestations despite treatment with a glucocorticoid dose >= prednisone 0.5 mg/kg/day (1 mg/kg po qod) for at least 4 weeks. 5.1.2 Any previous treatments for cGVHD (except nilotinib). Participants may have received nilotinib for other reasons besides cGVHD such as leukemia or solid tumor. 5.1.3 Participants must be receiving baseline systemic glucocorticoid therapy for cGVHD at study entry. The dose of steroids must be stable for 14 days prior to starting nilotinib. 5.1.4 At the time of trial enrollment, participants may be receiving one or two other immunosuppressive therapies in addition to glucocorticoids. Immunosuppressant doses must be stable for 14 days prior to starting nilotinib. Monoclonal T or B cell antibodies must be discontinued at least 28 days before starting nilotinib. 5.1.5 Chronic GVHD manifestations that can be followed on physical or laboratory exam. A list of potential manifestations is presented in Appendix D. 1. Skin changes 2. Oral mucosa changes 3. Hepatic dysfunction 5.1.6 >= 18 years old 5.1.7 Life expectancy >= 6 months. 5.1.8 Karnofsky performance status >= 60 (defined as being unable to work, able to live at home, and able to care for most personal needs but requiring occasional assistance from others). 5.1.9 Laboratory parameters: 1. Creatinine < 1.5 x ULN 2. ANC > 1.5 x 10^9/L 3. Platelets > 100 x 10^9/L 4. Total bilirubin < 1.5 x ULN 5. AST (SGOT) and ALT (SGPT) < 2.5 x ULN 6. Serum amylase and lipase <= 1.5 x ULN 7. Alkaline phosphatase <= 2.5 x ULN 8. Patients must have the following laboratory values within normal limits at the local institution lab or corrected to within normal limits with supplements prior to the first dose of study medication: Potassium Magnesium Phosphorus Calcium 5.1.10 Oxygen saturation during exertion maintained at >= 88% on room air. 5.1.11 Ability to understand and willingness to sign a written informed consent form. 5.1.12 Females with reproductive potential must have a negative pregnancy test <= 7 days before starting nilotinib. Reproductive potential will be defined as having at least 1 menstrual period in the past 12 months. Male and female subjects with reproductive potential agree to the use of barrier contraception during their treatment and for up to 3 months after the last dose. 5.1.13 Careful rationalization of concomitant medications with the intent to discontinue or change to alternative medications when any concomitant medications are identified that have the potential to prolong the QTcB interval or are associated with an increased risk of torsades de pointes. (Appendix B) 5.1.14 . Careful rationalization of concomitant medications with the intent to discontinue or change to alternative medications if any concomitant medications are identified to be strong CYP3A4 inhibitors. (Appendix C) 5.1.15 Myeloablative or non-myeloablative allogeneic hematopoietic cell transplant. Other eligibility criteria may apply. Exclusion Criteria: 5.2.1 Currently receiving or has received within 28 days of starting study drug nilotinib or any other tyrosine kinase inhibitor. 5.2.2 Received any anti-T or anti-B cell monoclonal antibody <= 28 days prior to the anticipated start of study drug. 5.2.3 Currently receiving > two immunosuppressants other than glucocorticoids. 5.2.4 Currently receiving a calcineurin inhibitor and sirolimus 5.2.5 Received any investigational agents <= 28 days before starting nilotinib. 5.2.6 Impaired cardiac function including any one of the following: 1. Clinically significant resting brachycardia (<50 beats per minute). 2. QTc > 450 msec on baseline ECG. If QTc >450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc. 3. Myocardial infarction within 12 months prior to starting study. 4. Other clinically significant uncontrolled heart disease (e.g. unstable angina, congestive heart failure or uncontrolled hypertension). 5. History of or presence of clinically significant ventricular or atrial tachyarrhythmias. (including congenital long QT syndrome or a known family history of congenital long QT syndrome) 5.2.7 Allogeneic cell infusion within 100 days 5.2.8 Uncontrolled infections not responsive to antibiotics, antiviral medicines, or antifungal medicines. 5.2.9 Progressive malignant disease including post transplant lymphoproliferative disease. 5.2.10 Any secondary malignancy except basal and squamous cell carcinoma of the skin within the past five years. 5.2.11 Nilotinib intolerance or hypersensitivity. 5.2.12 Impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection or gastric bypass surgery). 5.2.13 Acute or chronic pancreatic disease 5.2.14 Major surgery within 4 weeks prior to Day 1 of the study or who have not recovered from prior surgery. 5.2.15 Subject is pregnant, breast-feeding, or of childbearing potential without a negative serum or urine pregnancy test within 7 days of enrollment. Male or female patients of childbearing potential unwilling to use effective contraceptive precautions throughout the trial. 5.2.16 Subject not willing to comply with treatment or response evaluation (including associated procedures such as skin biopsy). 5.2.17 Subject has a concurrent illness which in the opinion of the investigator may interfere with the treatment and evaluation of the patient. Other exclusion criteria may apply. 4a305973dc06a058dc03440f3e54a223 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 RATIONALE: 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. PURPOSE: This phase II trial is studying the side effects and how well giving clofarabine together with low-dose total-body irradiation works in treating patients with acute myeloid leukemia undergoing donor peripheral blood stem cell transplant 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 - 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 FAB M3 in 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 HIV+ (HIV+ patients registered at 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 - DLCO < 40% (corrected), TLC < 40%, FEV1 < 40% 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 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 has to be =< 1.0 mg/dL; if not measured creatinine clearance should be equal 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 - Patients with systemic, uncontrolled infection - 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 amphotorecin 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 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. 322d9307d9df75a1b4927e5319208d1d 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 - Patients must have 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 x-rays, or hypercalcemia) and meet one of the following requirements: - 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]); OR - Have progressive disease on primary therapy with or without prior autologous stem cell transplant; OR - Have 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 - 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: - 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 - 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: - Left ventricular ejection fraction less than 35 percent - Corrected diffusion capacity of carbon monoxide (DLCO) less than 35 percent 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 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; 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. d149e27669c10fd5dc6f7d474472b736 8485 AKT Kinase Inhibitor MK-2206 With Relapsed Refractory Acute Myelogenous Leukemia II Roland Walter, MD 2466.00 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.8485.html http://www.clinicaltrials.gov/ct/search?term=NCT01253447 NCT01253447 The goal of this clinical research study is to learn if MK-2206 can help to control AML that has come back or has not responded to treatment. The safety of this drug will also be studied. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Patients must have histologically or cytologically confirmed AML other then acute promyelocytic leukemia - Patients must have persistent or relapsing disease requiring 2nd salvage therapy (e.g. treatment for second relapse or for primary refractory disease after failure of two prior treatment regimens); duration of prior complete remission <12 months if not refractory disease. Patients with prior autologous and allogeneic hematopoietic stem cell transplantation are eligible if patients are off immunosuppression for >1 month and have no evidence of active graft versus host disease (GVHD) except grade 1 skin GVHD. - Patient at the time of enrollment should not be a candidate for allogeneic stem cell transplantation. - Patient is male or female and >/=18 years of age on the day of signing informed consent. - ECOG performance status </=2 - Patient must have adequate organ function as indicated by the following laboratory values: Serum creatinine or calculated creatinine clearance</=1.5 x upper limit of normal (ULN) OR >/=60 mL/min for patients with creatinine levels >1.5 x institutional ULN; Serum total bilirubin </=2 x ULN OR direct bilirubin </= ULN for patients with total bilirubin levels >2 x ULN, unless elevation is thought to be due to hepatic infiltration by AML, Gilbert's syndrome, or hemolysis; AST (SGOT) and ALT (SGPT) </=2.5 x ULN or </=5 x ULN unless considered to be secondary to leukemic involvement; Fasting serum glucose</=150 mg/dl; HBA1C <=9%. - Female patient of childbearing potential must have a negative serum or urine pregnancy test beta-hCG within 72 hours prior to receiving the first dose of study medication. - Patient, or the patient's legal representative, has voluntarily agreed to participate by giving written informed consent. - Patient is able to swallow capsules and has no surgical or anatomical condition that will preclude the patient from swallowing and absorbing oral medications on an ongoing basis. Other eligibility criteria may apply. - Patients may not be receiving any other investigational agents. - Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1, without complete recovery. - Active uncontrolled infection. - Patients with CNS involvement - Systemic chemotherapy (with the exception of hydroxyurea) within 14 days (or within 5 half-lives for an investigational agent) prior to first dose of study drug, unless there is evidence of rapidly progressive disease. Persistent chronic clinically significant toxicities from prior chemotherapy must not be > grade 1. - Patient has known hypersensitivity to the components of study drug or its analogs. - Patient has a history or current evidence of clinically significant heart disease including: 1) Uncontrolled congestive heart failure, unstable angina pectoris, 2) uncontrolled cardiac arrhythmia, 3) history or current evidence of a myocardial infarction during the last 6 months, 4) QTc prolongation >450 msec (Bazett's Formula), 5) congenitally long QT syndrome, and/or has received any marketed or experimental compound in the last 4 weeks or 5 half lives (whichever is shorter) prior to entering the study with possible or known effects of QT prolongation. - Patient with evidence of symptomatic bradycardia, or a history of clinically significant bradyarrhythmias such as sick sinus syndrome, 2nd degree AV block (Mobitz Type 2). - Patient with uncontrolled hypertension (i.e., BP >/= 160/90 mHg ). Patients who are controlled on antihypertensive medication will be allowed to enter the study. - Patient with poorly controlled diabetes defined as HBA1C >9%. - Patient is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study. - Patient is known to be Human Immunodeficiency Virus (HIV)-positive with history of AIDS defining conditions; or CD4 cells prior to leukemia onset </= 400 cells/mm3; or patients receiving antiretroviral therapy that affects CYP3A4 such as protease inhibitors, efavirenz, nevirapine, or zidovudine Patient has active Hepatitis B or C or active Hepatitis A. Other exclusion criteria may apply. d52a40f524f941dda666563a7ff003ed 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; 43; 48; 64 Chronic Lymphoid Leukemia (CLL); 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. - 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 >= 1500/mm^3 - Platelet count (transfusion independent) >= 50,000/mm^3 - Creatinine clearance >= 30ml/min by Cockcroft-Gault formula - Total bilirubin =< 1.5 x upper limit of normal (ULN) - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine transaminase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 3 x ULN - 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. 9e5d38021da181c5241a3818dcfb5e07 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 Purpose 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 fludarabine phosphate, 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 with advanced AML defined as beyond first remission, primary refractory disease, or evolved from MDS or myeloproliferative syndromes; or patients with 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 Patients must have normal hepatic function (bilirubin, aspartate aminotransferase [AST] and alanine transaminase [ALT] < 2 times the upper limit of normal [ULN]) 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 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: - Sibling donor. A patient and sibling donor should be matched for HLA-A, B, C, DRB1 and DQB1 by an intermediate resolution DNA-based method. - 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 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 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 Women of childbearing potential who are pregnant (beta-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. 215f40ce109887be1fcec367cd816f08 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 8637 Lenalidomide in Treating Patients With AIDS-Related Kaposi Sarcoma I/II Corey Casper 2507.00 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.8637.html http://www.clinicaltrials.gov/ct/search?term=NCT01057121 NCT01057121 RATIONALE: Lenalidomide may stop the growth of tumor cells by blocking blood flow to the tumor. PURPOSE: This phase I/II trial is studying the side effects and best dose of lenalidomide and to see how well it works in treating patients with AIDS-related Kaposi sarcoma. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both DISEASE CHARACTERISTICS: • Biopsy-confirmed Kaposi sarcoma (KS) involving skin with or without visceral involvement o Newly diagnosed or refractory to or intolerant of one or more prior therapies • Must have cutaneous lesion(s) amenable to four 3-mm tumor biopsies during the study (either 4 separate lesions measuring > 4 mm each OR 2 separate lesions measuring > 8 mm each) and at least five additional lesions measurable for assessment with no improvement over the past month o Patients should have a sufficient number of non-indicator lesions available for biopsy of a size that will permit four 3-mm tumor biopsies during the study (two biopsies will be performed on Day 1 prior to treatment and two biopsies will be performed on Day 15) (the two biopsies can be performed on two separate non-indicator lesions measuring > 4 mm OR performed on one non-indicator lesion measuring >8 mm in size) • No evidence of improvement in KS within the past 3 months, unless there is evidence of progression of KS within the past 4 weeks • No requirement for front-line therapy (i.e., symptomatic visceral or pulmonary KS or symptomatic KS impairing functional status) • Serologically confirmed HIV infection by any of the FDA-approved tests o CD4 count > 50/mm^3 AND viral load < 2,000 copies/mL o Must be on a stable antiretroviral therapy regimen for HIV infection for = 12 weeks before study entry - Any FDA-approved antiretroviral therapy (except for zidovudine) allowed - Patients whose antiretroviral regimen contains zidovudine and whose viral load is suppressed (viral load = 200 copies/mL) are eligible provided their antiretroviral therapy is adjusted to a less toxic therapy not containing zidovudine (study enrollment may proceed without waiting 12 weeks) - Patients whose antiretroviral regimen contains zidovudine and whose viral load is not suppressed (viral load = 200 copies/mL) are eligible provided their antiretroviral therapy is adjusted to a less toxic regimen not containing zidovudine AND they are stable for = 12 weeks before study entry (allowing for optimal viral suppression) PATIENT CHARACTERISTICS: • Karnofsky performance status 60-100% • Life expectancy = 3 months • Hemoglobin = 8 g/dL (transfusion independent) • ANC = 1,000/mm^3 • Platelet count = 100,000/mm^3 • Calculated creatinine clearance = 60 mL/min (for patients enrolled in phase I) OR = 30 mL/min (for patients enrolled in phase II) • Total bilirubin = 1.5 times upper limit of normal (ULN) (= 3.5 mg/dL for patients with elevated bilirubin secondary to atazanavir therapy provided the direct bilirubin is normal) • AST and ALT = 3 times ULN • Not pregnant or nursing • Negative pregnancy test • Fertile patients must use effective double-method contraception for = 28 days before, during, and for = 28 days after completion of study treatment • Able to comply with study treatment, in the opinion of the investigator • No other primary malignancy within the past 2 years except for basal cell skin cancer, cervical carcinoma in situ, or anal carcinoma in situ • No other neoplasia requiring cytotoxic therapy • No pulmonary embolism (PE) or deep vein thrombosis (DVT) within the past year o History of PE or DVT or predisposing clotting risk factors are allowed provided patient is receiving anticoagulation at therapeutic dosing • No acute infection (other than oral thrush or genital herpes) requiring treatment within the past 14 days • No concurrent, acute, active opportunistic infection (other than oral thrush or genital herpes) within the past 14 days • No other serious medical illness within the past 14 days • No physical or psychiatric condition that, in the opinion of the investigator, would place the patient at high-risk of toxicity or non-compliance PRIOR CONCURRENT THERAPY: • See Disease Characteristics • No prior local therapy for any KS-indicator lesion unless the lesion has clearly progressed since treatment o Any prior local treatment to indicator lesions (regardless of the elapsed time) is not allowed unless there is evidence of clear-cut progression of that lesion(s) • More than 4 weeks since prior and no other concurrent antineoplastic treatment for KS (including chemotherapy, radiotherapy, local therapy [including topical fluorouracil], biological therapy, or investigational therapy) • No concurrent steroid treatment except steroids as replacement therapy for adrenal insufficiency or inhaled steroids for the treatment of asthma • No concurrent zidovudine • Concurrent erythropoietin-stimulating agents allowed provided patient is on therapeutic anticoagulation Other eligibility criteria may apply. Other exclusion criteria may apply. 0af21d5f33fd285711509d0c76fe2278 8755 High-Dose Cyclophosphamide and Anti-Thymocyte Globulin Followed by Peripheral Blood Stem Cell Transplant in Treating Patients With Systemic Scleroderma 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 Purpose This phase II trial studies how well giving cyclophosphamide and anti-thymocyte globulin together followed by peripheral blood stem cell transplant (PBSCT) works in treating patients with systemic Sclerosis. Stem cells are collected from the patient's blood and stored prior to treatment. To store the stem cells patients are given colony-stimulating factor, 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. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy and immunosuppression. 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, d or e - 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 for evaluation by the evaluation resource center (ERC) - c) Presence of SSc-related pulmonary disease with forced vital capacity (FVC) < 80% or hemoglobin-adjusted diffusing capacity for carbon monoxide (DLCO)1 < 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: - e) 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 plts/mm3 - 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 CT or 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) - Patients in group 3 must have a left ventricular ejection fraction of > 50% by Doppler echocardiography or multi gated acquisition scan (MUGA) scan - If arrhythmias are evident clinically, then an evaluation by a cardiologist is required GROUP 4: - Diffuse scleroderma with disease duration =< 2 years and skin score >= 30 - Patients in group 4 must have a left ventricular ejection fraction of > 50% by Doppler echocardiography or MUGA scan - If arrhythmias are evident clinically, then an evaluation by a cardiologist is required 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 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 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 cathertization is indicated; prior history of PAH but controlled with medications will not exclude patients from the protocol - 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 - 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] < 3x ULN) is allowed - The presence of anti-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. 18c130ecc9e178eb4b69b273ef80a7d4 8794 Cyclophosphamide for Preventing Graft-Versus-Host Disease After Peripheral Blood Stem Cell Transplant in Patients With Hematological Malignancies II Marco Mielcarek, MD 2541.00 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.8794.html http://www.clinicaltrials.gov/ct/search?term=NCT01427881 NCT01427881 Purpose This phase II trial studies how well cyclophosphamide works for preventing graft-versus-host disease after peripheral blood stem cell transplant in patients with hematological malignancies. Giving chemotherapy and total-body irradiation before a 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 cyclophosphamide after transplant may stop this from happening. Ages Eligible for Study: up to 65 Years Genders Eligible for Study: Both - Acute lymphocytic leukemia (ALL) in first complete remission (CR1) with high risk features defined as evidence of adverse cytogenetics such as t(9;22), t(1;19), t(4;11), or mixed-lineage leukemia (MLL) rearrangements or presence of minimal residual disease - Acute myeloid leukemia (AML) in CR1 with high risk features defined as: - Greater than 1 cycle of induction therapy required to achieve remission - Preceding myelodysplastic syndrome (MDS) other than myelofibrosis, secondary AML - Presence of fms-related tyrosine kinase 3 (Flt3) mutations or internal tandem duplications - French-American-British (FAB) M6 or M7 classification or adverse cytogenetics for overall survival such as those associated with MDS, M6, M7 leukemia - Complex karyotype [>= 3 abnormalities], inv(3), t(3;3), t(6;9), t(6;11), t(11;19)(q23;p13.1), + 8 [alone or with other abnormalities except for t(8:21), t(9;11), inv(16)] - 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) - MDS with following high risk features: - Poor cytogenetics (7q- or complex cytogenetics) - International Prognostic Scoring System (IPSS) intermediate (INT)-2 or greater - Treatment-related MDS - Any phase of MDS if patient is < 21 years of age - Chronic myelogenous leukemia (CML) beyond 1st chronic phase or resistant 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 donor 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 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%; 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) - Measured serum creatinine clearance =< 60 mL/min - 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. fbea7631166ad8e109e435069c9adabe 1998 II Tia Higano, MD 30296 30; 71; 83 Genitourinary Cancer; Prostate Cancer; Solid Tumors Jacqueline Sprinkle 206/288-1189 http://www.fhcrc.org/en/treatment/clinical-trials/detail.1998.html http://www.clinicaltrials.gov/ct/search?term=NCT00223665 NCT00223665 8d4c75be306eaae199d572861e8421f3 7618 NA Monique Cherrier, PhD 30824 71; 83 Prostate Cancer; Solid Tumors Tom Erickson, MA 206/277-1058 http://depts.washington.edu/memoryhg/ 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. a4cecd13fd8e08ed8096d2088e5d9812 6365 Cisplatin and Radiation Therapy With or Without Erlotinib Hydrochloride in Treating Patients With Stage III or Stage IV Head and Neck Cancer II Renato Martins, MD, MPH 6106 35; 42; 44; 56; 76; 83; 89; 90 Head and Neck Cancer; Laryngeal Cancer; Lip and Oral Cavity Cancer; Mouth Cancer; Salivary Gland Cancer; Solid Tumors; Thyroid Cancer; Tongue Cancer Sarah Wallace swallace@seattlecca.org 206/288-7487 http://www.fhcrc.org/en/treatment/clinical-trials/detail.6365.html http://www.clinicaltrials.gov/ct/search?term=NCT00410826 NCT00410826 The purpose of this study is to determine the safety and effectiveness of treating patients who have advanced head and neck cancer with the drug erlotinib, given in addition to the drug cisplatin and radiotherapy. This research is being done to compare the effects, good and/or bad, of treatment with erlotinib, cisplatin and radiotherapy, versus the current, standard treatment, which uses cisplatin and radiotherapy alone. This study will compare two groups of participants: One group will receive the standard treatment of cisplatin and radiotherapy alone; the other group will receive the drug erlotinib in addition to the standard treatment. Assignment to either group of participants is random (by chance). Most of the care will be given at the Seattle Cancer Care Alliance (SCCA) outpatient clinic. If hospitalization is needed while in Seattle, participants will be admitted to the University of Washington Medical Center (UWMC). Treatment on the study will last 6-8 weeks. All participants will receive the chemotherapy drug cisplatin once every 3 weeks for a total of three times, and radiation treatment for 6 weeks. Those participants who are randomly selected to receive erlotinib will take one erlotinib pill every day throughout the radiation treatment period. Once chemotherapy and radiation treatment are completed, all participants will receive standard care appropriate for the stage and location of the disease. 1. Patient has stage III or stage IV squamous cell carcinoma of the head and neck that is inoperable. 2. Patient is 18 years of age or older. 3. Male and female patients with reproductive potential must be willing to use an acceptable contraceptive method. 4. Patient has authorization from a dentist to begin radiation therapy. Other eligibility criteria may apply. 1. Other cancer in past 5 years (except non-melanoma skin cancer) 2. Congestive heart failure 3. Chronic diarrhea 4. Prior radiation, chemotherapy, or investigational treatment for head and neck cancer 5. Pregnant or breastfeeding women Other exclusion criteria may apply. 97a187a0f2af1e1d5b4765af8378e835 6954 Sunitinib Malate, Paclitaxel, Doxorubicin Hydrochloride, and Cyclophosphamide Before Surgery in Treating Patients With Stage IIB-IIIC Breast Cancer II Jennifer Specht, MD 6488 13; 83 Breast Cancer; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.cancer.gov/cancertopics/druginfo/sunitinibmalate http://www.fhcrc.org/en/treatment/clinical-trials/detail.6954.html http://www.clinicaltrials.gov/ct/search?term=NCT00513695 NCT00513695 Purpose This phase II trial studies how well giving sunitinib malate together with paclitaxel, doxorubicin hydrochloride, and cyclophosphamide before surgery works in treating patients with stage IIB-IIIC breast cancer. Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor. Drugs used in chemotherapy, such as paclitaxel, doxorubicin hydrochloride, and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving sunitinib malate together with combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed Genders Eligible for Study: Both - Be informed of the investigational nature of the study and all pertinent aspects of the trial and must sign and give written consent in accordance with institutional and federal guidelines - Have a histologically-confirmed diagnosis of breast cancer that is locally advanced or inflammatory; inflammatory breast cancer is defined as erythema and peau d'orange involving half or more of the breast with a histologic diagnosis of breast cancer; the finding of focal dermal lymphatic involvement on histology does not constitute inflammatory breast cancer - Have selected stage IIB (T3, N0, M0) or IIIA (T3, N1-2, M0 or T0-2, N2, M0) disease judged primarily unresectable by an experienced breast surgeon or otherwise deemed appropriate candidates for neoadjuvant treatment or stage IIIB (T4, any N, M0) or stage IIIC (any T, N3, M0) disease - Patients must have a performance status of 0-2 by Zubrod criteria - Absolute neutrophil count (ANC) >= 1,500 cells/mm^3 - Platelet count >= 100,000 cells/mm^3 - Serum creatinine =< 1.5 x institutional upper limit of normal (IULN) Bilirubin =< 2.0 - Serum glutamic oxaloacetic transaminase (SGOT)/serum glutamic pyruvic transaminase (SGPT)/alkaline phosphatase =< 2.0 x IULN - Have a multi gated acquisition scan (MUGA) or echocardiogram scan performed within 3 months prior to enrollment and have a left ventricular ejection fraction (LVEF) % greater than the institutional lower limit of normal - Be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other trial procedures Other eligibility criteria may apply. - Have evidence of distant metastases - Have tumors that overexpress human epidermal growth factor receptor 2 (HER2)/neu as evidenced by 3+ staining by immunohistochemistry or gene amplification by fluorescent in situ hybridization (FISH) - Have received any prior chemotherapy or hormonal therapy for breast cancer - Have received prior radiation therapy or prior definitive surgery for breast cancer - Have a clinical diagnosis of congestive heart failure or angina pectoris or any of the following within the 6 months prior to study drug administration:, myocardial infarction, coronary/peripheral artery bypass graft, cerebrovascular accident or transient ischemic attack, or pulmonary embolism - Have ongoing cardiac dysrhythmias of National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 3.0 grade >= 2 - Have uncontrolled hypertension (>150/100 mm Hg despite optimal medical therapy) - Have pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication - Have a known, active infection - Have any prior malignancy except for adequately treated basal cell or squamous cell skin cancer, any in situ cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission or any other cancer from which the patient has been disease-free for 5 years - Human immunodeficiency virus (HIV) positive - Are receiving or planning to receive any concurrent anticancer therapy while receiving protocol treatment - Are receiving or planning to receive concurrent treatment on another clinical trial (supportive care trials or non-treatment trials, e.g. quality of life (QOL) are allowed; participation in the companion imaging trial, dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) and fludeoxyglucose F 18 positron emission tomography (FDG PET) with Kinetic Analysis to Monitor Breast Cancer Response to Neoadjuvant Sunitinib and Metronomic Chemotherapy is also allowed) - Be pregnant or breast feeding; female subjects must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of therapy; all female subjects with reproductive potential must have a negative pregnancy test (serum or urine) prior to enrollment; male subjects must be surgically sterile or must 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 - Have other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study Other exclusion criteria may apply. df64cc3acde00c36f63dd98c922e5d37 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 Purpose 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 (American Joint Committee on Cancer [AJCC] 6th Ed.); resectability is determined by the treating surgeon and published guidelines (National Comprehensive Cancer Network v2.2006) - 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) - 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 - 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 - 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. 162eb0b04b427645a2861932f784d5bf 7129 Topical Imiquimod and Abraxane in Treating Patients With Advanced Breast Cancer II Lupe Salazar, MD 6578 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.7129.html http://www.clinicaltrials.gov/ct/search?term=NCT00821964 NCT00821964 Purpose This phase II trial is studying the side effects of giving topical imiquimod together with Abraxane (paclitaxel albumin-stabilized nanoparticle formulation) to see how well it works in treating patients with advanced breast cancer. Biological therapies, such as imiquimod, may stimulate the immune system to kill tumor cells. Drugs used in chemotherapy, such as Abraxane, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving imiquimod together with Abraxane may kill more tumor cells. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Patients with advanced stage refractory breast cancer - Progressive or relapsed disease following standard therapy with chemotherapy and/or surgery, and/or radiation - Patients must have measurable (bi-dimensional) chest wall disease and/or cutaneous metastatic lesions - Patients must be at least 7 days from last chemotherapy and 30 days from local radiotherapy and/or systemic steroids - Patients on bisphosphonates, trastuzumab, lapatinib and/or hormonal therapy are eligible - White blood cell count >= 1000/ul - Absolute neutrophil count (ANC) >= 1200/ul - Platelets > 75,000/ul - Serum creatinine =< 2.0 mg/dL, a creatinine clearance > 60 ml/min - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2 X upper limit normal (ULN) - Total bilirubin < 2 X ULN - Patients must have a Performance Status Score (Eastern Cooperative Oncology Group [ECOG] Scale) =< 2 - Patients must have recovered from major infections and/or surgical procedures and, in the opinion of the investigator, not have a significant active concurrent medical illness precluding protocol treatment - Men and women of reproductive ability must agree to contraceptive use during the study and for 1 month after imiquimod/Abraxane treatment is discontinued Other eligibility criteria may apply. - Patients with prior allergic reaction to taxanes - Patients with any clinically significant active autoimmune disease requiring active treatment with systemic steroids or other immunomodulators - Pregnant or breast-feeding women - Patients with peripheral neuropathy >= Grade 2 Other exclusion criteria may apply. c7ef80cdcd698c9c06e6987c5d64af20 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 The purpose of this research study is to determine whether or not the combination of the drugs nab-paclitaxel (Abraxane®), bevacizumab (Avastin®) and erlotinib (Tarceva®) is effective as treatment for breast cancer. In this study, we want to learn what effects, good or bad, this treatment has on people with a specific type of breast cancer called “triple negative breast cancer” that has spread to other parts of the body. The combination of the 3 drugs (Abraxane, Avastin and Tarceva) together in this research study is considered an investigational treatment. The length of study treatment is expected to be about 16 months. The study will take three and a half to four years to complete. Participants in this study will receive treatment at the Seattle Cancer Care Alliance outpatient clinic every week for the first 6 months, and then every other week for the next 10 months. During the first 6 months of study treatment, participants will receive nab-paclitaxel weekly and bevacizumab every other week. Both drugs are given intravenously (IV, by injection into a vein). If the cancer is stable or responding to treatment after the first 6 months, the participant will continue to receive bevacizumab intravenously every other week and will also take erlotinib by mouth every day for about 10 more months. After completion of study treatment, patients will be contacted periodically for follow-up. • 18 years or older • Diagnosed with breast cancer that has spread to other parts of the body (metastatic disease) and has the following “triple-negative” characteristics: - Estrogen receptor-negative - Progesterone receptor-negative - HER2/neu non-overexpressing • Planning to receive first-line therapy for metastatic disease Other eligibility criteria may apply. • Recurrent disease within 12 months after completion of adjuvant chemotherapy containing a weekly taxane • Central Nervous System (CNS) metastases Other exclusion criteria may apply. 748d576ca45f9446a25a309021a5c608 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 The purpose of this research study is to evaluate the safety and effects, good or bad, of an experimental procedure called adoptive T cell therapy. This study also includes treatment with an experimental vaccine. This study is for subjects with stage IV breast cancer that over-expresses the HER2 protein and is not completely responding to conventional therapy. There are several components to this study, including: weekly vaccines; leukapheresis procedure; chemotherapy; weekly T-cell infusions; booster vaccines; imaging and follow-up assessments. Treatment on this study (vaccines, chemotherapy, T-cell infusions and booster vaccines) will last about 7 months. Initial follow-up will continue for about 2 years, and long-term follow-up will continue for as long as the study participant will allow. All procedures will take place at the University of Washington Medical Center and possibly the Puget Sound Blood Center. We will then ask the participant's primary physician to keep us informed about the participant's health and send us blood samples on a regular basis. - Diagnosis of HER2+, Stage IV breast cancer that has been maximally treated and not achieved a complete remission - Disease is stable, measurable and not considered curable by conventional therapies - Subjects may be currently receiving trastuzumab and/or lapatinib and/or hormonal therapy and/or bisphosphonate therapy - Must be off of chemotherapy and steroids for at least 14 days before starting this study - Must be 18 years or older - If subject has a history of brain metastases, he or she must have a stable head imaging study within 30 days of enrollment Other eligibility criteria may apply. - Any indications that the patient is allergic or very sensitive to GM-CSF in vaccine products - Concurrent enrollment in other treatment studies - Pregnant or breast-feeding women - Active brain metastases - Cardiac disease - Immune system disorders such as HIV Other exclusion criteria may apply. 06419414b83fdf9c6d13f23960ab8bbb 7519 Bendamustine Hydrochloride in Treating Patients With Recurrent or Progressive Anaplastic Glioma II Marc Chamberlain, MD 6803 6; 12; 33; 83 Astrocytomas; Brain Cancer; Glioma; Solid Tumors Fereshteh Assadian 206/288-6693 https://catalyst.uw.edu/workspace/stonesk/14504/79546 http://www.fhcrc.org/en/treatment/clinical-trials/detail.7519.html http://www.clinicaltrials.gov/ct/search?term=NCT00823797 NCT00823797 The purpose of this study is to find out what effects (good and bad) the anti-cancer medication bendamustine has on treating brain cancers (Recurrent High-Grade Gliomas). This is an experimental treatment. Study participants will receive infusions of the drug, bendamustine, for six months or until the cancer returns or grows. Infusions of the study drug take place on two consecutive days each month. Participants will be asked to return for follow-up visits every other month for up to three years after starting treatment. This research study is conducted at the University of Washington Medical Center and Seattle Cancer Care Alliance. - Brain tumor that has been diagnosed as a recurrent high-grade glioma (anaplastic gliomas). - Other criteria will be evaluated by the physician, nurse, and study coordinator to determine whether the study is right for individual patients. Other eligibility criteria may apply. - Criteria will be evaluated by the physician, nurse, and study coordinator to determine whether the study is right for individual patients. Other exclusion criteria may apply. 3d008d4c4ecde454a163e17d3c5bc98e 7596 Vorinostat in Treating Patients With Stage IV Breast Cancer Receiving Aromatase Inhibitor Therapy Pilot Hannah Linden, MD 6856 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.7596.html http://www.clinicaltrials.gov/ct/search?term=NCT01153672 NCT01153672 RATIONALE: Vorinostat may may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Vorinostat may also help aromatase inhibitor therapy work better by making tumor cells more sensitive to the drug. PURPOSE: This clinical trial studies vorinostat in treating patients with stage IV breast cancer receiving aromatase inhibitor therapy. 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 AI or other endocrine therapy, but is no longer deriving benefit to AI therapy in the opinion of the treating investigator; patients need to stop the AI for at least one week prior to starting vorinostat treatment on this protocol - At least one site of measurable disease, as defined by the modified RECIST Criteria - ECOG performance status 0-2 - Female patient is either post menopausal, free from menses for >= 2 years, surgically sterilized or willing to use 2 barrier methods of contraception (such as IUD, diaphragm, condom) to prevent pregnancy or agrees to abstain from heterosexual activity throughout the study - Female patient of childbearing potential has a negative serum or urine pregnancy test within 7 days prior to receiving the first dose of vorinostat - Female patient that is pre-menopausal must be on ovarian suppression therapy - 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 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 and magnesium levels within normal limits - Calculated creatinine clearance >= 30 mL/min - Serum total bilirubin =< 1.5 X ULN - AST (SGOT) and ALT (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 - Patient is willing to continue on same AI therapy - Patient agrees to participate in imagining Protocol 7184 Other eligibility criteria may apply. - Patient has not derived clinical benefit from any previous hormonal therapy (e.g. tamoxifen or aromatase inhibitor) - 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) - Patient has received an ER blocking therapy (selective estrogen receptor modulating or downregulating SERM or SERD i.e. tamoxifen or fulvestrant) within the past 30 days - Patient had prior treatment with an 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 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 - 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 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. 340d98b8e507be45391cf7d55597ee00 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 - 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. 294cdb839bf9a5c44140110bd3b8e391 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 Central Nervous System (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 RATIONALE: 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-CSF liposomal cytarabine may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving high-dose methotrexate together with liposomal cytarabine works in treating patients with CNS metastases from metastatic breast cancer. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Female - Women 18 years or older who are not pregnant (contraception must be used throughout the study) - Diagnosis of breast cancer with metastases to CNS (regardless of receptor status) - 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 MRI and CSF cytology - Karnofsky Performance Status > 60 - Acceptable bone marrow function as documented by history and current complete blood counts (CBC): WBC > 3.0 K, ANC > 1.5 K, PLT > 100 K, HCT > 30 % - Acceptable renal function (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 enrolment will be allowed to continue) - Bisphosphonates (i.e., zolendronic acid) will be allowed - Mini-mental status examination score of 24 or above - Enzyme-inducing anti-seizure medications are allowed, however, when possible non-enzyme inducing drugs should be selected - In Her2/Neu positive patients, continuation of trastuzumab or lapatinib for systemic disease may continue at the discretion of the treating physician - Steroids are allowed 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 < 4.0 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 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 - 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 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 - During therapy with HD-MTX and for 1- 2 days before and 2-3 days following discharge from the hospital patients are not allowed to take non-steroidal anti-inflammatory medications including aspirin or sulfa compounds. Patients should avoid citrus fruit (grapefruit, oranges, lemons, and limes) and acidic fruits and fruit juices (cranberry, etc.) - No other intrathecal medications in addition to liposomal cytarabine are allowed during therapy - In general, systemic chemotherapy (other than high-dose methotrexate) will not be allowed while on study Other exclusion criteria may apply. 066280913ed33167cd9d9e88086ce139 7882 Combination Chemotherapy in Treating Patients With Stage III or Stage IV Malignant Peripheral Nerve Sheath Tumors II Eve Rodler, MD 7007 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.7882.html http://www.clinicaltrials.gov/ct/search?term=NCT00304083 NCT00304083 RATIONALE: Drugs used in chemotherapy, such as doxorubicin, ifosfamide, and etoposide, 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. Giving combination chemotherapy with or without radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving combination chemotherapy after surgery may kill any tumor cells that remain after surgery. PURPOSE: This phase II trial is studying how well combination chemotherapy works in treating patients with stage III or stage IV malignant peripheral nerve sheath tumors. Genders Eligible for Study: Both DISEASE CHARACTERISTICS: - Newly diagnosed sporadic or neurofibromatosis type 1 (NF1)-associated high-grade malignant peripheral nerve sheath tumors (MPNSTs) - Stage III or stage IV (metastatic) disease - Measurable disease, defined as at least 1 tumor that is measurable in 2 dimensions on CT scan or MRI PATIENT CHARACTERISTICS: - Ejection fraction normal by echocardiogram or MUGA - Serum creatinine normal for age OR creatinine clearance > 60 mL/min - SGPT < 5 times upper limit of normal (ULN) - Bilirubin < 2.5 times ULN - Absolute neutrophil count = 1,500/mm^3* - Hemoglobin = 9.0 g/dL* - Platelet count = 100,000/mm^3* - ECOG performance status 0-2 - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for 6 months after completion of study treatment NOTE: * Unsupported PRIOR CONCURRENT THERAPY: - No prior chemotherapy for MPNST - Prior surgical resection of MPNST allowed provided residual or recurrent measurable disease is present - Recovered from toxic effects of all prior therapy - At least 3 weeks since prior chemotherapy or biologic therapy for treatment of a plexiform neurofibroma, optical pathway tumor, or other NF1-associated tumor (in patients with NF1) - At least 6 weeks since prior radiotherapy for treatment of a plexiform neurofibroma, optical pathway tumor, or other NF1-associated tumor (in patients with NF1) - At least 4 weeks since prior radiotherapy to the area involved by MPNST - No other concurrent growth factors (e.g., sargramostim [GM-CSF] or interleukin-11) - Concurrent epoetin alfa allowed Other eligibility criteria may apply. Other exclusion criteria may apply. 8583f4537fd6c5b6e226417d1377bf10 7883 A Placebo-Controlled Study of Saracatinib (AZD0530) in Patients With Recurrent Osteosarcoma Localized to the Lung II Eve Rodler, MD 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. df0e0f1c3a4ea3b238d98f61ed7203d2 8007 Abiraterone Acetate, Prednisone, and Leuprolide Acetate or Goserelin Before and During Radiation Therapy in Treating Patients With Localized or Locally Advanced Prostate Cancer II Robert Montgomery, MD 7048 30; 71; 83 Genitourinary Cancer; Prostate Cancer; Solid Tumors Mark Konodi 206/359-5227 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8007.html http://www.clinicaltrials.gov/ct/search?term=NCT01023061 NCT01023061 Purpose RATIONALE: Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as abiraterone acetate, leuprolide acetate, and goserelin, may lessen the amount of androgens made by the body. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving abiraterone acetate and leuprolide acetate or goserelin before or together with radiation therapy may be an effective treatment for prostate cancer. PURPOSE: This phase II trial is studying the side effects and how well giving abiraterone acetate, prednisone, and leuprolide acetate or goserelin before and during radiation therapy works in treating patients with localized or locally advanced prostate cancer Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Male - Willing and able to provide written informed consent - Patients must allow biopsy prior to neoadjuvant therapy and at the time of fiducial placement - Written Authorization for Use and Release of Health and Research Study Information has been obtained - Histologically proven adenocarcinoma of the prostate - Patients must be candidates for short or long term androgen deprivation in combination with external beam radiotherapy (RT) based on the following criteria: - Intermediate Risk Disease: T2b/c, or Gleason 7, or PSA 10-20 - High Risk Disease: Gleason 8-10, or PSA > 20, or T3/4 - Patients may not have received any prior pharmacologic therapy or RT for prostate cancer - Eastern Cooperative Oncology Group (ECOG) performance status =< 2 - Karnofsky >= 60% - Eligibility of patients receiving any medications or substances known to affect or with the potential to affect the androgen axis will be determined following review of their case by the Principal Investigator - White blood cell count: >= 3,000/mm^3 - Absolute granulocyte count: >= 1,000/mm^3 - Platelets: >= 100,000/mm^3 - Hemoglobin >= 10g/dL - Potassium >= 3.5 mmol/L - Serum creatinine: =< 1.5 x upper limit of normal (ULN) - Aspartate aminotransferase (AST) < 2.5 x ULN - Alanine transaminase (ALT) < 2.5 x ULN - Total bilirubin: =< 1.5 x ULN (except for patients with documented Gilbert's disease) Other eligibility criteria may apply. - Patients may not be receiving any investigational agents - Concurrent enrollment in another clinical investigational drug or device study is prohibited - The concurrent administration of other anticancer therapy, including cytotoxic or hormonal agents (except LHRH agonists), or immunotherapy, is prohibited during neoadjuvant concurrent and adjuvant therapy - 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 - Patients with hypogonadism or severe androgen deficiency as defined by serum testosterone less than 100 ng/dL will not be eligible - History of pituitary or adrenal dysfunction - Patients who are receiving any androgens, estrogens or progestational agents, or who received any of these agents within the 6 months prior to evaluation will not be eligible - Patients who are taking drugs which affect androgen metabolism (e.g. spironolactone, ketoconazole, finasteride, dutasteride) will not be eligible - Concomitant therapy with any of the following listed is prohibited: 5 alpha-reductase inhibitor (finasteride, dutasteride); ketoconazole, diethylstilbestrol, PC-SPES, and other preparations such as saw palmetto thought to have endocrine effects on prostate cancer; radiopharmaceuticals such as strontium (89Sr) or samarium (153Sm); Aldactone, Spironol (spironolactone); estrogens, testosterone, progesterones, herbal medications - Patients who received any of these agents within the 6 months prior to evaluation will be reviewed for eligibility by the Principal Investigator on a case by case basis - Use of other investigational drug therapy for any reason is prohibited - Patients with inflammatory bowel disease or other autoimmune conditions which might affect the radiated colon or rectum - Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris, cardiac arrhythmia which is symptomatic or requires active therapy, recent deep venous thrombosis, pulmonary emboli, cerebrovascular accident or ischemia will not be eligible - Patients who have chronic active hepatitis or acute hepatitis will not be eligible - 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 medical conditions, which, in the opinion of the investigators, would jeopardize either the patient or the integrity of the data obtained will not be eligible - Uncontrolled hypertension within the screening period (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 therapy - History of congestive heart failure of any severity - Other active malignancy, except non-melanoma skin cancer and superficial bladder cancer - History of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug - Patients with diabetes not controlled with diet alone (i.e. requiring insulin or oral hypoglycemics) - Patients unwilling to use contraceptives while on study Other exclusion criteria may apply. ad236e1fd0ea3ea490843be5baf49511 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. 4d0321563c3876f2b1f029d97809e20d 8188 Clofarabine, Cytarabine, and G-CSF in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia or Advanced Myelodysplastic Syndrome II Pamela Becker, MD, PhD 7144 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.8188.html http://www.clinicaltrials.gov/ct/search?term=NCT01101880 NCT01101880 RATIONALE: Drugs used in chemotherapy, such as clofarabine and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving the drugs in different doses may kill more cancer cells. Colony stimulating factors, such as G-CSF, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy. Giving clofarabine and cytarabine together with G-CSF may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving clofarabine and cytarabine together with G-CSF works in treating patients with newly diagnosed acute myeloid leukemia or advanced myelodysplastic syndrome. Ages Eligible for Study: 18 Years to 65 Years Genders Eligible for Study: Both - Diagnosis of acute myeloid leukemia by WHO criteria (except acute promyelocytic leukemia), or myelodysplastic syndrome with >= 10% blasts, RAEB-2 by WHO classification - ECOG Performance Status 0 - 2 - Adequate renal and hepatic function as indicated by the following laboratory values: - Serum creatinine =< 1.0 mg/dL; if serum creatinine > 1.0 mg/dL, then the estimated glomerular filtration rate (GFR) must be > 60 mL/min/1.73 m^2 as calculated by the Modification of Diet in Renal Disease equation - Serum bilirubin =< 1.5 x upper limit of normal (ULN) - Aspartate transaminase (AST) =< 2.5 x ULN - Alanine transaminase (ALT) =< 2.5 x ULN - Alkaline phosphatase =< 2.5 x ULN - Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent - Female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment - Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment Other eligibility criteria may apply. - Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol with the exception of intrathecal chemotherapy administered on days that are not concurrent with clofarabine and cytarabine - No prior anti-leukemia therapy other than 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 significant organ compromise due to systemic fungal, bacterial, viral, or other infection - Pregnant or lactating patients - Any significant concurrent illness, condition, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results - Have had a diagnosis of another malignancy, unless the patient has been disease-free for at least 3 years following the completion of curative intent therapy including the following: A) Patients with treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, regardless of the disease-free duration, are eligible for this study if definitive treatment for the condition has been completed; B) Patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen (PSA) values are also eligible for this study if hormonal therapy has been initiated or a radical prostatectomy has been performed - Prior allogeneic stem cell transplant - No concomitant cytotoxic therapy or investigational therapy is allowed during the study Other exclusion criteria may apply. 2a6922ced8aa42e6a5f31479538d7f2c 8222 Veliparib, Cisplatin, and Vinorelbine Ditartrate in Treating Patients With Recurrent and/or Metastatic Breast Cancer I Eve Rodler, 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 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 previously 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. b87a7e3fc623047acf12b024ce0f0537 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: I. To determine the safety of an insulin like growth factor binding protein 2 (IGFBP-2) Th polyepitope plasmid based vaccine in patients with advanced stage ovarian cancer. II. To determine the immunogenicity of IGFBP-2 Th polyepitope plasmid based vaccine in patients with advanced stage ovarian cancer. SECONDARY OBJECTIVES: I. To determine whether intermolecular epitope spreading occurs with the generation of an IGFBP-2 specific Th1 immune response. II. To determine whether IGFBP-2 vaccination modulates T regulatory cells. OUTLINE: Patients receive pUMVC3-hIGFBP-2 multi-epitope plasmid DNA vaccine intradermally (ID) monthly for 3 months. After completion of study treatment, patients are followed up at 1, 3, 6, and 12 months, and then yearly for 15 years. • Patients with advanced stage ovarian cancer, stages III or IV, who have been treated to complete remission with standard therapies • Patients must be at least 14 days post cytotoxic chemotherapy, and/or monoclonal antibody therapy, prior to enrollment • Patients must be at least 14 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/mm^3 • 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. 9ad2f1b552a75a145af1607a7dca6da5 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; 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.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 (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 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 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 within the previous 3 weeks or palliative radiation therapy within the previous 2 weeks; major surgery within the past 4 weeks prior to dosing with cetuximab or VTX-2337; patients should have recovered from major toxicities of prior therapy - Concurrent symptomatic central nervous system (CNS) involvement, brain or meningeal 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 Other exclusion criteria may apply. 3e2b8a14d180265f59821f5cb7c3706c 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 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 - 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. a89d388f99135ce7648b1e7265664b70 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: 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 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 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 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 hysterectomy A bilateral oophorectomy (ovariectomy); a bilateral tubal ligation 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: 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 Oral contraceptive, either combined or progestogen alone Injectable progestogen Implants of levonorgestrel Estrogenic vaginal ring Percutaneous contraceptive patches Intrauterine device (IUD) or intrauterine system (IUS) with a documented failure rate of less than 1% per year 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 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 - Prior exposure to receptor tyrosine kinase inhibitors and anti-angiogenic agents in the metastatic setting is not allowed - 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: Active peptic ulcer disease Known intraluminal metastatic lesion/s with risk of bleeding 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 - 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 - 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: Cardiac angioplasty or stenting Myocardial infarction Unstable angina Coronary artery bypass graft surgery Symptomatic peripheral vascular disease 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; 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 - 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: Radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of pazopanib OR 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. 223a86b8c143b067542f67fa186d03c5 8908 Abiraterone Acetate Combined With Dutasteride for Metastatic Castrate Resistant Prostate Cancer II Robert Montgomery, MD 7621 30; 71; 83 Genitourinary Cancer; Prostate Cancer; Solid Tumors Sara Teller 206/598-0854 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8908.html http://www.clinicaltrials.gov/ct/search?term=NCT01393730 NCT01393730 The purpose of this research study is to determine if the addition of dutasteride to a regimen with abiraterone acetate and prednisone will improve on therapy in patients with castrate-resistant prostate cancer and metastatic disease. This study will also help determine the side effects of the study treatment and how often they occur. Patients will receive abiraterone acetate and prednisone orally, once daily for 2 months (2 cycles) on an outpatient basis. At the start of cycle 3, dutasteride will be taken once daily. Patients will return to the clinic on Day 14 of the first 3 cycles for routine blood tests. Patients will come to the clinic every 12 weeks for a CT scan and/or x-ray of the chest, CT scan or MRI of the abdomen and pelvis, bone scan, and blood test for testosterone and other specialized blood test. - Diagnosis of adenocarcinoma of the prostate - Castrate resistant disease - Metastatic disease - Normal organ and marrow function - Subjects with partners of childbearing potential must be willing to use adequate methods of birth control Other eligibility criteria may apply. - Uncontrolled intercurrent illness - Uncontrolled hypertension - Active or symptomatic viral hepatitis or chronic liver disease - History of pituitary or adrenal dysfunction - Clinically significant heart disease - History of a different malignancy unless disease-free for at least 5 years - Known brain metastasis - History of gastrointestinal disorders - Prior therapy with abiraterone acetate - HIV-positive individuals on antiretroviral therapy - Requirement for steroid use greater than the equivalent of 5 mg of prednisone daily - Atrial fibrillation or other cardiac arrhythmia requiring therapy - Thromboembolism in the last 6 months Other exclusion criteria may apply. 4a75fef45d7b726429b2fdb4ad5bb4b1 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 6853 Study Looking at Effectiveness of I-131-Tositumomab (Bexxar) Consolidation for Patients With Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) II John Pagel, MD, PhD PSOC 2301 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.6853.html http://www.clinicaltrials.gov/ct/search?term=NCT00476047 NCT00476047 This study is evaluating the use of radioimmunotherapy given to patients whose B-Cell Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) is in first remission. (The initial treatment, standard chemotherapy, is not part of this study.) The purpose of this research treatment is to determine the safety and effects, good or bad, of using radioimmunotherapy to try and eliminate any remaining disease and to lower the chance of the CLL/SLL from returning. Radioimmunotherapy uses an antibody that is designed to target specific cancer cells such as the CLL/SLL cells, and deliver a small targeted dose of radiation to them. The use of radioimmunotherapy in this study is investigational. Study participants will receive the radiolabeled antibody called 131I-tositumomab (also called Bexxar®) at the University of Washington Medical Center (UWMC) or Seattle Cancer Care Alliance (SCCA). Treatment with 131I-tositumomab can be given as an outpatient. It requires 4 to 5 visits to a nuclear medicine physician at the UWMC during a 1 to 2 week period. During this time, study participants will receive a dose of 131I-tositumomab, then have 3 whole-body scans performed and then receive another dose of 131I-tositumomab. Participants will be asked to visit their study doctor for follow-up exams for at least 5 years. • Age 18 or older • Diagnosed with CD20+ CLL or SLL (prior to first treatment had either Rai stage III/IV disease or Rai stage I/II with evidence of disease activity) • Patient received prior therapy and is in 1st remission with a partial or complete response to treatment • Patient has no more than 25% of marrow space involved by leukemia Other eligibility criteria may apply. • Prior treatment with radiolabeled antibody • Active hemolysis • Receiving sustained transfusion support of blood products • In 2nd remission or beyond • Prior treatment with either stem cell or bone marrow transplant • Active obstructive hydronephrosis Other exclusion criteria may apply. 839bc91f82de5aa4a28b81fb18ced070 7686 Vorinostat, Fludarabine Phosphate, Cyclophosphamide, and Rituximab in Treating Patients With Previously Untreated B-Cell 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 study is evaluating the use of the drug vorinostat when given in addition to standard treatment (fludarabine, cyclophosphamide and rituximab) in patients with B-cell Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL). The purpose of this study is to: 1) Determine how much of the drug vorinostat can be given safely in combination with the standard chemotherapy of fludarabine, cyclophosphamide and rituximab. 2) Determine whether or not adding vorinostat to standard treatment followed by rituximab plus vorinostat maintenance therapy can improve response to treatment and prevent the CLL/SLL from coming back. 3) Determine the effects, good or bad, of using vorinostat in combination with the other chemotherapy drugs. Study participants will receive treatment at the University of Washington Medical Center (UWMC) or Seattle Cancer Care Alliance (SCCA). The length of treatment in this study will be about 2 ½ years. Fludarabine, cyclophosphamide, rituximab and vorinostat therapy will be received during the first 6 months. Following that, maintenance therapy with rituximab and vorinostat will be received for two years. • Age 18 or older • Diagnosed with CD20+ chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), meeting one of the following stage criteria: - Stage I or II disease with evidence of disease activity - Stage III or IV disease • Have not received previous treatment for CLL or SLL Other eligibility criteria may apply. • Prior cytotoxic chemotherapy, radiotherapy, immunotherapy, or cytokine therapy for CLL or SLL • Prior stem cell or bone marrow transplant • Active hemolysis • Receiving sustained transfusion support with blood products • Active obstructive hydronephrosis • Brain or leptomeningeal involvement by malignancy Other exclusion criteria may apply. 9b822ea5f78c422ccea4843ca74ca661 8021 II Oliver Press, MD, PhD SWOG 0816 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.8021.html http://www.clinicaltrials.gov/ct/search?term=NCT00822120 NCT00822120 43312c2bd88653acb84e8b2970df7c23 2237 Donor Lymphocyte Infusion in Treating Patients With Persistent, Relapsed, or Progressing Cancer After Donor Hematopoietic Cell Transplant I/II Brenda Sandmaier, MD 1803.00 1; 2; 19; 36; 38; 40; 43; 48; 57; 64 Acute Lymphoid Leukemia (ALL); Acute Myeloid Leukemia (AML); Chronic Myeloid Leukemia (CML); Hematologic Malignancies; Hodgkin's Lymphoma; Juvenile Myeloid Leukemia (JML); 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.2237.html http://www.clinicaltrials.gov/ct/search?term=NCT00068718 NCT00068718 RATIONALE: White blood cells from donors may be able to kill cancer cells in patients with cancer that has come back after a donor hematopoietic cell transplant. PURPOSE: This clinical trial studies donor lymphocyte infusion in treating patients with persistent, relapsed, or progressing cancer after donor hematopoietic cell transplantation Genders Eligible for Study: Both - Only patients having received a preceding nonmyeloablative allogeneic transplantation with fludarabine/2 Gy total-body irradiation (TBI) - 4 Gy TBI or 2 Gy TBI - 4 Gy TBI conditioning from either a related or unrelated donor are eligible for this protocol - Patients with persistent, relapsed or progressing malignancy after nonmyeloablative allogeneic transplantation (persistent disease will be defined as a failure to achieve a response as compared to baseline) - Patients with rapidly progressing malignancies (acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), blastic phase chronic myelogenous leukemia (CML-BC), intermediate-high-grade non-Hodgkin lymphoma (NHL), Hodgkins disease or aggressive multiple myeloma (MM)) should receive salvage chemotherapy or radiation before DLI according to the recommendation made in this protocol; any form of salvage chemotherapy should be discontinued no less than 3 weeks before DLI; therapy with Gleevec or IFN-alpha should be discontinued prior to DLI; after salvage chemotherapy restaging is performed, patients with progressive disease and patients not meeting the inclusion criteria of the study after chemotherapy will be excluded from the study; patients are allowed to receive further doses of chemotherapy after DLI administration if they are scheduled for further DLI; after additional therapy the patients must be restaged and must again meet inclusion criteria to receive further DLI - Patients must be able to tolerate a taper of systemic steroids to a dosage of less than or equal to 0.25 mg/kg/day; all other immunosuppressive therapy must have been discontinued for at least two weeks without significant flares in GVHD (i.e., increase of acute GVHD by one or more grades) - Patients must have persistent donor CD3 cells (> 5% donor CD3 cells by a DNA-based assay that compares the profile of amplified fragment length polymorphisms [ampFLP or FISH studies or 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 DLI product must be from the original donor of hematopoietic cell transplantation - 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 for pediatric patients - DONOR: Donors 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. 071d9cc040a9c4d18b27299cfdc05be9 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 RATIONALE: 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. PURPOSE: This clinical trial studies pentostatin and donor lymphocyte infusion in preventing graft rejection in patients who have undergone donor stem cell transplant 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 DNA-based assay that compares the profile of amplified fragment length polymorphisms [ampFLP] [or FISH studies or VNTR]) - DONOR: Alternatively to a fresh unmodified leukapheresis product, previously collected cryopreserved peripheral blood stem cells (PBSC) after mobilization with G-CSF or crypreserved unmodified leukapheresis product from the original donor can be used; if cryopreserved product is not available, the DLI product must be from the original donor of hematopoietic cell transplantation. - 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. 107fba8068a81af8ebae18820cc1263b 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 Purpose 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 (David G Maloney, 206-667-5616 or Brenda Sandmaier, 206-667-4961) - 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. 63d071386bcce82a35fb742528691372 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 The purpose of this study is to learn more about the effects, good and bad, of stem-cell transplantation that uses umbilical cord blood as the stem-cell source. This study is for subjects who are 45 years of age or younger, and who do not have a suitably matched stem cell donor. Analysis of the effects of transplants helps us improve transplant outcomes in the future. As part of the transplant process, participants will receive high doses of chemotherapy and radiation to treat their underlying disease. This chemotherapy and radiation treatment also kills the healthy blood stem cells that are already in the bone marrow. Participants will receive blood stem cells from the umbilical cord of a healthy donor to help recover the bone marrow. 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. Participants 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 the transplantation (after about 3 months) will be according to the participant’s specific type of disease. Visits to the participant’s physician will likely be scheduled 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 2 years after the transplant. 1. Participant is 45 years of age or younger (must be at least 6 months old). 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 (according to study guidelines); b. Chronic myelogenous leukemia (except refractory blast crisis); c. Advanced myelofibrosis; d. Myelodysplastic syndrome with severe pancytopenia or complex cytogenetics; e. Large-cell lymphoma (according to study guidelines); f. Lymphoblastic, Burkitt’s and other high grade lymphomas; g. Mantle-cell lymphoma, lymphoplasmacytic lymphoma, and prolymphocytic leukemia may be eligible after initial therapy; h. Multiple myeloma (according to study guidelines). Other eligibility criteria may apply. 1. Over 45 years of age (or under 6 months). 2. A suitably matched, related or unrelated donor is available. 3. Pregnancy or breastfeeding. 4. Evidence of HIV infection. 5. Uncontrolled viral or bacterial infection at the time of study enrollment. 6. Active or recent (prior 6 month) invasive fungal infection without ID consult and approval. 7. Presence of acute leukemia that has returned or is persistent. 8. Presence of large cell and high grade non-Hodgkins lymphoma that has not responded to previous treatment with chemotherapy (progressive disease after more than 2 salvage regimens). 9. If 18 years of age or younger, prior myeloablative transplant within the last 6 months. 10. If older than 18 years of age, prior myeloablative allotransplant or autologous transplant. 11. Extensive prior therapy including more than 12 months of alkylator therapy, or more than 6 months of alkylator therapy with extensive radiation. Other exclusion criteria may apply. 1cf7314af07ad68a6f3ef1727413a5e6 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. fa7d01f5a4922d5ab1bd6ee5fad67631 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: - come back after first remission, or - did not respond to initial treatment, or - evolved from myelodysplastic or myeloproliferative syndrome • MDS patients must have one of the following: - refractory anemia with excess blasts (RAEB), - RAEB in transformation (RAEBT), - refractory cytopenia with multilineage dysplasia (RCMD), - RCMD with ringed sideroblasts (RCMD-RS), or - 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. a87f3474cc0d1165490caa84f20b060a 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 RATIONALE: 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. PURPOSE: This phase II trial is studying how well giving sirolimus together with cyclosporine and mycophenolate mofetil works in preventing graft-vs-host disease in patients with hematologic malignancies undergoing donor peripheral blood stem cell transplant. 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 TRM); this criterion can include patients with a HCT-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 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 PI (Brenda Sandmaier, MD 206 667 4961) 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 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 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 - 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 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 any single class II locus (HLA-DRB1 or - DQB1); 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: a) 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 - DONOR: b) mismatched for two HLA class I alleles, but matched for HLA-DRB1 and HLA-DQ, OR - DONOR: c) mismatched for one HLA-DRB1 antigen or allele with or without an additional mismatch for one 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 G-CSF mobilized PBSC only will be permitted as a HSC source on this protocol Other eligibility criteria may apply. - Patients who are homozygous at the mismatched 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 CMML - Patients with 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 - 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 - 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 - 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%; ejection fraction is required if the patient is > 50 years of age, or history of cardiac disease or anthracycline exposure - Corrected DLCO < 40%, TLC < 40%, 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 - 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. 24b27a706026c096268527b2a1613952 7575 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 d38794df9aa3952cc0c2f90509b84f51 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 RATIONALE: 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. 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 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 not eligible for autologous HCT; not eligible for high-dose HCT; or after failed autologous HCT - 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 failed front-line therapy and either failed or not be eligible for autologous HCT - 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) - ( > int- 1 per International prostate symptom score [IPSS]) after > or = 1 prior cycle of induction chemotherapy; must have < 5% marrow blasts at time of transplant - Waldenstroms 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 2. 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 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 - 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. 5886450290334ab737fd240c0b2fd3ef 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 RATIONALE: 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. 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. 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 - MCL, T-NHL, or other high-risk malignancies may be enrolled/transplanted in CR/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 CT imaging for purposes of planar and/or 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 (Cr < 2.0) and normal hepatic function (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 - 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 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 BMT (e.g. abnormally decreased cardiac ejection fraction, DLCO < 50% predicted, FEV1 < 70% predicted, AIDS, etc.) - Known HIV seropositivity - Pregnancy or breast feeding - Prior allogeneic bone marrow or stem cell transplant - Prior autologous bone marrow or stem cell transplant or prior 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 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) - 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. e31146d8ddc3f03b911adac36c77aa8e 7293 Unrelated 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 RATIONALE: Giving chemotherapy and total-body irradiation 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. PURPOSE: This phase II trial is studying how well umbilical cord blood transplant from an unrelated donor works in treating patients with hematological cancer 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% - 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: Must have < 5% morphologic marrow blasts in an evaluable marrow (>25% of normal cellularity for age) at the time of transplant - Acute Lymphoblastic Leukemia: Must have < 5% morphologic marrow blasts in an evaluable marrow (> 25% of normal cellularity for age) at the time of 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; 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 therapy pre-transplant to reduce blast count to =< 5% - 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 - Donors: 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 - Donors: The patient and the cord blood unit(s) must be matched for at least 4 of 6 loci as defined above - Donors: 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 or available 10/10 matched unrelated 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 - Donors: Any cord blood units with < 1.5 x 10^7 total nucleated cells per kilogram recipient weight - Donors: 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. d4d0e9e431facc9f7ebf8b7c789805a9 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 RATIONALE: 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 cancer cells. These donated stem cells may help destroy cancer cells (graft-versus-tumor effect). PURPOSE: 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 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 Ages Eligible for Study: up to 75 Years Genders Eligible for Study: Both Must have the capacity to give informed consent Detectable tumor on radiographic studies or bone marrow biopsy prior to mobilization regimen 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 Patients with stored autologous stem cells will be allowed Stem cells from an identical donor could be used for autologous HCT 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 i) Diagnosis of NHL or HL, of any histological grade, ii) Refractory or relapsed disease after standard chemotherapy, iii) High risk of early relapse following autograft alone Waldenstrom's Macroglobulinemia: must have failed 2 courses of therapy CLL: i) Patients with either a: - Diagnosis of T-cell CLL or T-cell PLL who have failed initial chemotherapy, or - Diagnosis of B-cell CLL, B-cell small lymphocytic lymphoma, or B-cell CLL that progressed to prolymphocytic leukemia (PLL) who either: 1) Failed to meet NCI Working Group criteria for complete or partial response after therapy with a regimen containing fludarabine (or another nucleoside analog, e.g. 2-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 FCR, at any time point 3) Have "17p deletion" cytogenetic abnormality and relapsed at any time point after initial chemotherapy ii) Harvesting criteria for autologous HCT: 4) previously collected PBMC may be used 5) circulating CLL cells < 5000 iii) Marrow involvement with CLL cells < 50% MM: Patients who: i) Have received induction therapy for a minimum of 4 cycles ii) In addition, patients must meet at least one of the following criteria I-IX (I-VII at time of diagnosis or pre-autograft): - Any abnormal karyotype by metaphase analysis except for isolated t(11,14), - FISH translocation 4:14, - FISH translocation 14:16, - FISH deletion 17p, - Beta2-microglobulin > 5.5 mg/ml, - Cytogenetic hypodiploidy - Plasmablastic morphology (>= 2%), - Recurrent or non-responsive (less than PR) MM after at least two different lines of conventional chemotherapy - progressive MM after a previous autograft (provided stored autologous CD34 cells are available) Plasma cell leukemia: after induction chemotherapy Donor Selection Inclusions: - 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 - Age < 75 yrs, older donors may be considered after review at Patient Care Conference Other eligibility criteria may apply. - Life expectancy severely limited by disease other than malignancy - Seropositive for the human immunodeficiency virus - Female patients who are pregnant or breastfeeding - Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment - Cross match positive with donor - Patients with available HLA matched related donors - 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 - Patients with fungal infection and radiological progression after receipt of amphotericin B or active triazole for greater than 1 month - Cardiac: Symptomatic coronary artery disease or ejection fraction < 40% or other cardiac failure requiring therapy; ejection fraction is required if the patient has a history of anthracyclines or history of cardiac disease - Pulmonary: Corrected DLCO < 50% of predicted, FEV1 < 50% of predicted, and/or receiving supplementary continuous oxygen - 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. 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 Selection: - Donor-recipient pairs in which the HLA-mismatch is only in the HVG direction; - Donors who are not expected to meet the minimum target dose of marrow cells (1 x 108 nucleated cells/kg recipient IBW); - Infection with HIV; - Weight < 20 kg; - A positive anti-donor cytotoxic crossmatch Other exclusion criteria may apply. dcd8f2edb77b9bc2b583557da1947f47 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, 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, 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 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 or readily available 10/10 matched unrelated 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 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. ba490ac578c598a73ba82aac7d6b3061 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 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 RATIONALE: 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 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. PURPOSE: This phase II trial is studying how well donor peripheral blood stem cell transplant works in treating patients with hematologic malignancies. Genders Eligible for Study: Both - Molecular based 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 CRp - Acute Lymphoblastic Leukemia in high risk CR1 as defined by at least one of the following: adverse cytogenetics such as t(9;22), t(1;19), t(4;11), 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 - OR adverse cytogenetics for overall survival such: 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 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 Flt3 abnormalities; or FAB M6 or M7 leukemia; - 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) - Patients with adequate physical function as measured by: - Cardiac: left ventricular ejection fraction at rest must be >= 35% - Hepatic: bilirubin =< 2.5 mg/dL - ALT < 5 x ULN - AST < 5 x ULN - Alkaline phosphatase < 5 x ULN - Renal: serum creatinine within normal range for age, or if serum creatinine outside normal range for age, then renal function (creatinine clearance or GFR) > 40 mL/min/1.73m^2 - Pulmonary: FEV1, FVC, DLCO (diffusion capacity) > 50% predicted (corrected for hemoglobin); if unable to perform pulmonary function tests, then O2 saturation > 92% on room air - Performance status: 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 INCLUSION CRITERIA: Donors must be HLA-haploidentical first-degree relatives of the patient; eligible donors include biological parents, siblings, or children, or half-siblings Other eligibility criteria may apply. - HLA-matched or single allele-mismatched donor able to donate - 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) - Patients with primary idiopathic myelofibrosis - DONOR EXCLUSION CRITERIA: Positive anti-donor HLA antibody Other exclusion criteria may apply. d66bfc56116ddd54b30d0486a2bfcf02 8329 Infusion of Off-the-Shelf Expanded Cord Blood Cells to Augment Cord Blood Transplant in Patients With Hematologic Malignancies II Colleen Delaney, MD, MSc 2378.00 1; 19; 36; 43; 61; 121 Acute Lymphoid Leukemia (ALL); Chronic Myeloid Leukemia (CML); Hematologic Malignancies; Leukemia; 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.8329.html http://www.clinicaltrials.gov/ct/search?term=NCT01175785 NCT01175785 RATIONALE: Chemotherapy, such as fludarabine and cyclophosphamide, and total-body irradiation given before an umbilical cord blood transplant stops the growth of leukemia cells and works to prevent the patient's immune system from rejecting the donor's stem cells. The healthy stem cells from the donor's umbilical cord blood help the patient's bone marrow make new red blood cells, white blood cells, and platelets. It may take several weeks for these new blood cells to grow. During that period of time, patients are at increased risk for bleeding and infection. Faster recovery of white blood cells may decrease the number and severity of infections. Studies have shown that counts recover more quickly when more cord blood cells are given with the transplant. We have developed a way of growing or "expanding" the number of cord blood cells in the lab so that there are more cells available for transplant. We are doing this study to find out whether or not giving these expanded cells along with one or two unexpanded cord blood units is safe and if use of expanded cells can decrease the time it takes for white blood cells to recover after transplant. We will study the time it takes for blood counts to recover, which of the two or three cord blood units makes up the patient's new blood system, and how quickly immune system cells return. PURPOSE: This phase II trial is studying the safety and potential efficacy of infusing non-human leukocyte antigen (HLA) matched ex vivo expanded cord blood progenitors with one or two unmanipulated umbilical cord blood units for transplantation following conditioning with fludarabine, cyclophosphamide and total body irradiation, and immunosuppression with cyclosporine and mycophenolate mofetil for patients with hematologic malignancies Ages Eligible for Study: 6 Months to 45 Years Genders Eligible for Study: Both - Acute myeloid leukemia: - High risk complete response (CR)1 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 CR, erythroblastic or megakaryocytic leukemia; >= 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 can not 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, Colleen Delaney 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; - 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 can not 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, Colleen Delaney 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 imatinib mesylate - Myelodysplasia International Prognostic Scoring System (IPSS) intermediate 2 (Int-2) or High risk (i.e., refractory anemia with excess myeloblasts [RAEB], refractory anemia with excess blasts in transformation [RAEB-T]) 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% - Lansky (< 16 years old) >= 50% - Calculated creatinine clearance must be > 60 mL and serum creatinine =< 2 mg/dL (adults) - Calculated creatinine clearance must be > 60 mL/min (children < 18 years old) - Total serum bilirubin must be < 3mg/dl and transaminases must be < 3 x the upper limit of normal - Diffusion capacity of carbon monoxide (DLCO) corrected > 50% normal; for pediatric patients unable to perform pulmonary function tests, O2 saturation > 92% on room air - 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. 4d175f14f3bc60a73e2c63ef42f0dc65 8360 Exercise and Stress Management Post Autologous and Allogeneic Transplant III Stephanie Lee, MD, MPH 2443.00 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.8360.html http://www.clinicaltrials.gov/ct/search?term=NCT01278927 NCT01278927 Purpose This is a Phase III, randomized, unblinded, multicenter, prospective comparative study. The purpose of this study is to test whether exercise or stress management training delivered to autologous and allogeneic hematopoietic cell transplantation (HCT) patients prior to transplantation can improve functional status and the transplant experience. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Able to speak and read English - Able to exercise at low to moderate intensity - adequate cardiopulmonary reserve, as judged by self-reported ability to walk up one flight of stairs, no requirement for supplemental oxygen, and physician judgment - Willing and able to provide informed consent. - Stated willingness to comply with study procedures and reporting requirements - Planned autologous or allogeneic transplantation within 6 weeks. Other eligibility criteria may apply. - Orthopedic, neurologic or other problems which prevent safe ambulation and protocol adherence - Participation in another clinical trial with quality of life or functional status as a primary endpoint Other exclusion criteria may apply. 47181ecba117297a0dbc82220db43896 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 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.8430.html http://www.clinicaltrials.gov/ct/search?term=NCT01231412 NCT01231412 RATIONALE: 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. PURPOSE: This phase II 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 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 PI (Brenda Sandmaier, MD 206 667 4961) 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. - 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 - 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-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-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; or - 4) 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 - 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 first chronic phase (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 - DONOR: Matched for human leukocyte antigen (HLA)-A, B, C, DRB1 and DQB1 by high resolution typing - DONOR: 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 Organ dysfunction: - Cardiac ejection fraction < 35%; ejection fraction is required if age > 50 years or there is a history of anthracycline exposure or history of cardiac disease - 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 - 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, 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 or ARM 3 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. 394708331846798341e76d89f428c78d 8787 CD19-specific Donor 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 target CD19 in patients who have had a matched related allogeneic hematopoietic stem cell transplant for a CD19+ B cell malignancy and are at high-risk of disease relapse after transplant. - Ages Eligible for Study: 18 Years to 75 Years - Genders Eligible for Study: Both - Patients with CD19+ B cell malignancy who are planned for peripheral blood stem cell transplant from an HLA-matched related donor after myeloablative or non-myeloablative conditioning on a Fred Hutchinson Cancer Research Center (FHCRC) transplant protocol and are at high risk of relapse after HCT defined by any one of the disease-specific criteria listed below: - Philadelphia chromosome negative acute lymphoblastic leukemia: - Beyond first complete remission (CR) at the time of pre-transplant evaluation - 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 - First CR with poor risk cytogenetics (t(4:11), t(8;14), hypodiploidy, near triploidy or > 5 cytogenetic abnormalities) at diagnosis - 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 - Mantle cell lymphoma:?Lymph nodes greater than or equal to 2 cm at the time of pre-transplant evaluation - 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 - 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. - Age greater than or equal to 18 years and less than or equal to 75 years Other eligibility criteria may apply. - Philadelphia chromosome positive acute lymphocytic leukemia - Central nervous system (CNS) tumor refractory to intrathecal chemotherapy and/or cranio-spinal radiation - Human immunodeficiency virus (HIV) seropositive - Significant medical or psychological conditions that would make them unsuitable candidates for allogeneic HCT and T cell therapy - Fertile patients unwilling to use contraception during and for 12 months after HCT - Pregnant or breast-feeding Other exclusion criteria may apply. 45e30771b90de77583f8f8fb04220c15 8826 A Multicenter Access and Distribution Protocol for Unlicensed Cryopreserved Cord Blood Units (CBUs) II 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. a6d04d3fe6814d06fa7e8f97ee9e370a 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; 48; 57 Hematologic Malignancies; Hodgkin's Lymphoma; 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 RATIONALE: Giving chemotherapy, such as bendamustine hydrochloride 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 G-CSF, and certain chemotherapy drugs helps stem cells move from the bone marrow to the blood so they can be collected and stored. PURPOSE: This phase II trial is studying how well giving bendamustine hydrochloride, dexamethasone, and filgrastim together for peripheral stem cell mobilization works in treating patients with refractory or recurrent lymphoma or multiple myeloma. 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 PI approval - WHO classification of patients' malignancies must be provided - Patients with multiple myeloma must have a serum protein electrophoresis with immunofixation; serum beta-2 microglobulin; serum free light chains; 24-hour urine collection for Bence-Jones protein (light chains) and monoclonal component by urine protein electrophoresis evaluated within one month of enrollment - Patients with lymphoid malignancies must have a CT of chest, abdomen, and pelvis within one month 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 - Bone Marrow Function: ANC >= 1,500/mm^3 - Platelets >= 100,000/mm^3 (without transfusion or growth factor support) - Renal Function: A creatinine clearance greater than 50/ml per minute by the following formula (all tests must be performed within 28 days prior to registration): CrCl = (140-age) (Wt in Kg) x 0.85 (female) OR 1.0 (male)/72 x serum Cr Hepatic function: - Total bilirubin < 1.5 times upper limit of normal - AST and 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 for apheresis procedure - Three or fewer prior myelotoxic treatment regimens (specific regimens include ICE, DHAP, MTX/HiDAC, hyperCVAD, VTD-PACE) Other eligibility criteria may apply. - Patients known positive for 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 who have previously demonstrated resistance to bendamustine therapy (i.e. no response or progression w/in 6 months) - Greater than four prior cycles of lenalidomide therapy - Fludarabine or other nucleoside analog (except gemcitabine or cytarabine) therapy within 24 months of registration - Symptomatic cardiopulmonary disease - Prior autologous or allogeneic transplantation - Prior radioimmunotherapy within 12 weeks of registration - Prior failed (< 5 x 10^6 CD34/kg) peripheral blood stem cell (PBSC) collection - Prior pelvic or spinal irradiation - Previous 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. 7662fcdc00ac7cadd61d08683b3b356e 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 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 RATIONALE: 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. PURPOSE: This phase I 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. 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's lymphoma), or untreated lymphomas that are not curable with anthracycline based therapy (e.g. MCL, FL, MZL, LPL); patients with other lymphomas that have not received any prior therapy and are not candidates for anthracycline based therapies, are eligible with PI review and approval - 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 CT, 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 ECOG performance status of 0, 1, or 2 - Adequate Bone Marrow Function: ANC >= 1,500/mm^3, platelets >= 100,000/mm^3 (without transfusion or growth factor support) - Adequate Renal Function: serum creatinine < 1.5 mg/dl or creatinine clearance greater than 50/ ml per minute - Adequate Hepatic function: total bilirubin < 1.5 times upper limit of normal, AST and ALT < 2.5 times upper limit of normal - Patients must have a serum 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 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 - Previous chemotherapy/immunotherapy within 3 weeks before study entry - Concurrent use of other anti-cancer agents or experimental treatments - Known hypersensitivity to bendamustine, mannitol, etopiside, carboplatin, or rituximab Other exclusion criteria may apply. 872a388fff23f485a47100d57fbe3573 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 8133 II George Laramore, MD, PhD 7060 12; 83; 126 Brain Cancer; Solid Tumors; Meningioma Marge Koe 206/598-4127 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8133.html http://www.clinicaltrials.gov/ct/search?term=NCT00895622 NCT00895622 7d2c83ffb63d1e39f2d01e654bf2e317 8343 II George Laramore, MD, PhD 7196 6; 12; 32; 33; 83 Astrocytomas; Brain Cancer; Glioblastoma Multiforme; Glioma; Solid Tumors Marge Koe 206/598-4127 http://www.rtog.org/; http://www.acrin.org; http://www.cancer.gov/ http://www.fhcrc.org/en/treatment/clinical-trials/detail.8343.html http://www.clinicaltrials.gov/ct/search?term=NCT01062425 NCT01062425 d053510bee74cc38d2948fc62716bd40 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 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 7283 III Fred Appelbaum, MD CTSU C140503 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.7283.html http://www.clinicaltrials.gov/ct/search?term=NCT00499330 NCT00499330 f8d704f1e91efd2edc22ce7f59c53626 7027 III Fred Appelbaum, MD CTSU C50303 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.7027.html http://www.clinicaltrials.gov/ct/search?term=NCT00118209 NCT00118209 1053bd9095f332341e8b4674e8f9b8a3 8720 II Fred Appelbaum, MD CTSU C50604 48; 64 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.8720.html http://www.clinicaltrials.gov/ct/search?term=NCT01132807 NCT01132807 14326e20087459a16a936e2f0bb4ca27 6548 III Fred Appelbaum, MD CTSU C80405 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.6548.html http://www.clinicaltrials.gov/ct/search?term=NCT00265850 NCT00265850 6f94580033ac803388ca3ee80d2fb576 6066 III Fred Appelbaum, MD CTSU C90202 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.6066.html http://www.clinicaltrials.gov/ct/search?term=NCT00079001 NCT00079001 4b4805ee5b64aef3030bc25aacfd4a26 7149 III Fred Appelbaum, MD CTSU E1505 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.7149.html http://www.clinicaltrials.gov/ct/search?term=NCT00324805 NCT00324805 e00b78975ea9d0183f0cb4389777c417 7785 II Fred Appelbaum, MD CTSU N0733 13; 83 Breast Cancer; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.ctsu.org/ http://www.fhcrc.org/en/treatment/clinical-trials/detail.7785.html http://www.clinicaltrials.gov/ct/search?term=NCT00684983 NCT00684983 069309bfcd01bb80a0f46eff722dafd3 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 dd55c92ccc0329a4de0390fb898b91dd 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 6996 III Fred Appelbaum, MD SWOG 0500 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.6996.html http://www.clinicaltrials.gov/ct/search?term=NCT00382018 NCT00382018 0dfeff8c0427fbe3e37d1864b7585884 7313 III Fred Appelbaum, MD SWOG 0518 28; 83; 140 Gastrointestinal Cancer; Solid Tumors; Neuroendocrine Tumor Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.7313.html http://www.clinicaltrials.gov/ct/search?term=NCT00569127 NCT00569127 88f544d2a473f136a36f23c1a2266685 7360 II Fred Appelbaum, MD SWOG 0535 3; 36; 43 Acute Promyeloid Leukemia (APL); Hematologic Malignancies; Leukemia Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.7360.html http://www.clinicaltrials.gov/ct/search?term=NCT00551460 NCT00551460 5c29bf2ce51c5a9d3ff1c80bbc8553dd 8209 NA Fred Appelbaum, MD SWOG 0702 13; 30; 36; 46; 57; 71; 83 Breast Cancer; Genitourinary Cancer; Hematologic Malignancies; Lung Cancer; Multiple Myeloma (MM); 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.8209.html http://www.clinicaltrials.gov/ct/search?term=NCT00874211 NCT00874211 46ccc2273fc401bbfaec62447a67ef6b 8039 II Fred Appelbaum, MD SWOG 0703 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.8039.html http://www.clinicaltrials.gov/ct/search?term=NCT00658814 NCT00658814 65604e66ca1773dffc6f1d16eeced6e5 8593 II Fred Appelbaum, MD SWOG 0709 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.8593.html http://www.clinicaltrials.gov/ct/search?term=NCT00661193 NCT00661193 21873df6f19598359e8357d6d61c7027 8038 I Fred Appelbaum, MD SWOG 0711 28; 45; 83 Gastrointestinal Cancer; 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.8038.html http://www.clinicaltrials.gov/ct/search?term=NCT00608361 NCT00608361 b148ccf9dd94ff3e9e1c7029534fce02 8029 II Fred Appelbaum, MD SWOG 0713 28; 73; 83 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.8029.html http://www.clinicaltrials.gov/ct/search?term=NCT00686166 NCT00686166 6028b312fffe48a5dc8b0e637630075f 8879 II Fred Appelbaum, MD SWOG 0800 13; 83 Breast Cancer; Solid Tumors Kim Conway 206/667-7141 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8879.html http://www.clinicaltrials.gov/ct/search?term=NCT00856492 NCT00856492 0b0d0b74c23c8fc6c49e537e7eb31da7 8880 II Fred Appelbaum, MD SWOG 0802 46; 83 Lung Cancer; Solid Tumors Kim Conway 206/667-7141 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8880.html http://www.clinicaltrials.gov/ct/search?term=NCT00828139 NCT00828139 9d13a68b4716e195fe9f7b0bd34c7e1f 8686 II Fred Appelbaum, MD SWOG 0805 1; 43 Acute Lymphoid Leukemia (ALL); Leukemia Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8686.html http://www.clinicaltrials.gov/ct/search?term=NCT00792948 NCT00792948 5b0ff229b83edb1f8fd3055a39b49372 8484 II Fred Appelbaum, MD SWOG 0809 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.8484.html http://www.clinicaltrials.gov/ct/search?term=NCT00789958 NCT00789958 0755a9b267d895070f77f3ea5248668e 8470 Carboplatin and Paclitaxel With or Without Bevacizumab and/or Cetuximab in Treating Patients With Stage IV or Recurrent Non-Small Cell Lung Cancer III Fred Appelbaum, MD SWOG 0819 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.8470.html http://www.clinicaltrials.gov/ct/search?term=NCT00946712 NCT00946712 38bb90838b48f28b16115d78243eb853 8881 II Fred Appelbaum, MD SWOG 0910 1; 36 Acute Lymphoid Leukemia (ALL); Hematologic Malignancies Kim Conway 206/667-7141 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8881.html http://www.clinicaltrials.gov/ct/search?term=SWOG+0910 SWOG+0910 2d91114a7e5cb07e972b6f2b3381a846 8442 II Fred Appelbaum, MD SWOG 0919 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.8442.html http://www.clinicaltrials.gov/ct/search?term=NCT00840177 NCT00840177 2f2c494e33a732740ade9fc1489e4de4 8642 II Evan Yu, MD SWOG 0925 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.8642.html http://www.clinicaltrials.gov/ct/search?term=NCT01120236 NCT01120236 b9fa403185887bbb9919da8e79ad9313 8882 III Fred Appelbaum, MD SWOG 0931 74; 83 Renal Cancer; Solid Tumors Kim Conway 206/667-7141 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8882.html http://www.clinicaltrials.gov/ct/search?term=NCT01120249 NCT01120249 bc175419a0bffc48b12d98dc94a6186d 7334 II Fred Appelbaum, MD SWOG C10403 1; 36; 43 Acute Lymphoid Leukemia (ALL); Hematologic Malignancies; Leukemia Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.7334.html http://www.clinicaltrials.gov/ct/search?term=NCT00558519 NCT00558519 012b4c0fe090170d32bf9ba530b674d7 8618 III Fred Appelbaum, MD SWOG C80702 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.8618.html http://www.clinicaltrials.gov/ct/search?term=SWOG+C80702 SWOG+C80702 5d39040a72f9f86169f9d6d8bbe4432a 8613 III Fred Appelbaum, MD SWOG C90601 30; 83 Genitourinary Cancer; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8613.html http://www.clinicaltrials.gov/ct/search?term=NCT00942331 NCT00942331 fd5551c19c10912779496a498e6c8838 8971 III Fred Appelbaum, MD SWOG E1609 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.8971.html http://www.clinicaltrials.gov/ct/search?term=SWOG+E1609 SWOG+E1609 adc29e086f036f3c1e40dcc6c937b700 8842 III Fred Appelbaum, MD SWOG MA.32 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.8842.html http://www.clinicaltrials.gov/ct/search?term=NCT01101438 NCT01101438 14b3fd0618b309cfa43bb2813976a93c 8841 II Fred Appelbaum, MD SWOG S1005 27; 28; 83; 84 Gastric Cancer; Gastrointestinal Cancer; Solid Tumors; Stomach Cancer Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8841.html http://www.clinicaltrials.gov/ct/search?term=NCT01260701 NCT01260701 8b3b02fd84510cdda8d97d072e5e4786 8931 II Fred Appelbaum, MD SWOG S1014 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.8931.html http://www.clinicaltrials.gov/ct/search?term=SWOG+S1014 SWOG+S1014 31d38fe0b475cddc66cde5be466d2654 7501 Trabectedin for Patients With Locally Advanced or Metastatic Soft Tissue Sarcoma III Eve Rodler, MD 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. 1d76bd33ccf65fa5054953ce28ff646c 7289 Phase III Lucanix™ Vaccine Therapy in Advanced Non-small Cell Lung Cancer (NSCLC) Following Front-line Chemotherapy (STOP) III Keith Eaton, MD, PhD 20062200 46; 83 Lung Cancer; Solid Tumors Libby Kell emkell@seattlecca.org 206/288-7445 http://www.fhcrc.org/en/treatment/clinical-trials/detail.7289.html http://www.clinicaltrials.gov/ct/search?term=NCT00676507 NCT00676507 This research study will compare the effectiveness and safety of an experimental vaccine, called Lucanix™, with placebo, in subjects with advanced stage, non-small cell lung cancer. Placebo is a look-alike liquid that has no medicine in it. Participants in this study will receive Lucanix™ or placebo, plus standard care for cancer. Study participants will receive treatment at the Seattle Cancer Care Alliance outpatient clinic. Participants will be randomly assigned (similar to flipping a coin) to receive Lucanix™ or placebo. All participants will receive monthly injections of either Lucanix™ or placebo in the arm for 18 months. After that, participants will receive 2 more injections, once every 3 months. Treatment on the study will last about 1 ½ to 2 years. After completion of study treatment, participants will have a follow-up appointment every 3 months for one year. After the initial follow-up visits, we will contact participants once a year for 4 years, by phone, to ask about their health. • Age 18-75 • Diagnosed with stage IIIA (T3N2 only), IIIB or IV, non-small cell lung cancer (NSCLC) • Cancer is stable or improved after previous, platinum-based chemotherapy • Chemotherapy must have ended at least one month, but not more than four months, before registration into this study Other eligibility criteria may apply. • Taking more than 2 mg per day of prednisone (or equivalent of other steroid) currently or less than 4 weeks prior to study registration • Prior surgery to remove the spleen • Any surgery involving general anesthesia less than 4 weeks prior to study registration • Chemotherapy more than 4 months or less than 4 weeks prior to study registration • Radiation therapy or immunotherapy less than 4 weeks prior to study registration • Objective evidence of brain metastases • Significant or symptomatic pleural effusions (water on the lungs) • Known allergies to eggs or soy • NCI CTC Grade 3 or 4 peripheral neuropathy (pain and numbness in hands and feet) Other exclusion criteria may apply. 18e96d788e7903a74bb96b0a75cee819 6949 Safety Study of an Antisense Product in Prostate, Ovarian, NSCL, Breast or Bladder Cancer I Evan Yu, MD 20070773 9; 13; 30; 34; 46; 65; 71; 83 Bladder Cancer; Breast Cancer; Genitourinary Cancer; Gynecological Cancer; Lung Cancer; Ovarian Cancer; Prostate Cancer; Solid Tumors Debbie Chielens, RN 206/288-1189 http://www.fhcrc.org/en/treatment/clinical-trials/detail.6949.html http://www.clinicaltrials.gov/ct/search?term=NCT00487786 NCT00487786 The purpose of this study is to determine the safety and effects (both good and bad) of an experimental drug called OGX-427 in patients with prostate, ovary, breast, bladder or non-small cell lung cancer which has spread to other places in the body (metastatic cancer). In this study we will try to find the the highest dose of OGX-427 that does not cause intolerable side effects (the maximum tolerated dose). After finding the maximum tolerated dose, we will study the safety and effects (both good and bad) of OGX-427 when taken in combination with a chemotherapy drug called docetaxel. Not all participants enrolled in this study will receive docetaxel. The study drug, OGX-427, is given as an infusion through a vein in the arm about once a week. Treatment with OGX-427 will continue for about 2 – 9 months, depending on the participant’s medical condition. Participants in this study will receive the study drug, OGX-427, at the Seattle Cancer Care Alliance (SCCA) outpatient clinic. If hospitalization is needed while in Seattle, participants will be admitted to the University of Washington Medical Center (UWMC). After treatment has stopped, we would like to follow-up with study participants every 2 months. 1. Age 18 years or older. 2. Diagnosis of one of the following: • Breast cancer • Prostate cancer • Ovarian cancer • Non-small cell lung cancer (NSCL) • Bladder cancer 3. Previous treatment has not been successful, or no treatment exists for the cancer. 4. Disease has spread beyond the original location (metastatic cancer). Other eligibility criteria may apply. • More than three cytotoxic chemotherapy regimens. (This does not include immunotherapy, non-cytotoxic experimental therapy, radiation therapy, hormone or estrogen therapy, steroids, tamoxifen and/or aromatase inhibitors). • Current treatment with any anticancer agent including (but not limited to) trastuzumab, aromatase inhibitors, or tamoxifen. Steroids, bisphosphonates and female hormone-replacement therapy are allowed. • Documented central nervous system (CNS) metastasis or carcinomatous meningitis. • Pregnancy or breastfeeding. • Current second malignancy except for non-melanoma skin cancers, superficial bladder cancer, early cervical cancer or early prostate cancer not requiring treatment. Other exclusion criteria may apply. 1522f75287260b150d306701c1a8130b 7624 A Phase 1 Study of MLN9708 in Adult Patients With Advanced Nonhematologic Malignancies I John Thompson, MD 20082188 35; 46; 71; 77; 83 Head and Neck Cancer; Lung Cancer; Prostate Cancer; Sarcoma; Solid Tumors Phase 1 Program, Study Line phase1@u.washington.edu 206/288-7551 http://www.fhcrc.org/en/treatment/clinical-trials/detail.7624.html http://www.clinicaltrials.gov/ct/search?term=NCT00830869 NCT00830869 This is an open-label, multicenter, phase 1, dose escalation study of MLN9708. The primary purpose of this study is to determine the safety profile, establish the maximum tolerated dose, and inform the phase 2 dose of MLN9708 administered intravenously in patients with nonhematologic malignancies. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both Each patient must meet all of the following inclusion criteria to be enrolled in the study: - Male or female patients 18 years or older - Eastern Cooperative Oncology Group performance status 0-2. - A diagnosis of a nonhematologic malignancy for which standard treatment is no longer effective. In the expanded cohort, enrollment will be limited to patients with a diagnosis of NSCLC, head and neck cancer (squamous cell cancer), soft tissue sarcoma, or prostate cancer. - Suitable venous access PK and pharmacodynamic evaluations - Female patients who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or abstain from heterosexual intercourse. - Male patients who agree to to practice 2 effective methods of contraception or abstain from heterosexual intercourse. - Voluntary written consent must be obtained. - Adequate clinical laboratory values during the screening period Other eligibility criteria may apply. Patients meeting any of the following exclusion criteria are not to be enrolled in the study: - Peripheral neuropathy =Grade 2 - Female patients who are lactating or have a positive serum pregnancy test during the screening period - Major surgery within 14 days before the first dose of treatment - Infection requiring systemic antibiotic therapy or other serious infection within 14 days before the first dose of study treatment - Life-threatening illness unrelated to cancer - Diarrhea >Grade 1 based on the NCI CTCAE categorization - Systemic antineoplastic therapy / or radiotherapy within 21 days before the first dose of study treatment - Systemic treatment with prohibited medications - Patient has symptomatic brain metastasis. - Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure (CHF), angina, or myocardial infarction within the past 6 months - QTc >470 milliseconds (msec) on a 12-lead electrocardiogram (ECG) obtained during the screening period. - Known human immunodeficiency virus (HIV), hepatitis B and hepatitis C positive - Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol - Treatment with any investigational products within 28 days before the first dose of study treatment Other exclusion criteria may apply. 2b39b01e8fdd026c0c1f2cf47d0a395b 8118 A Phase II Study to Evaluate Efficacy and Safety of P276-00 in Relapsed and/or Refractory Mantle Cell Lymphoma II Ajay Gopal, MD 20091274 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.8118.html http://www.clinicaltrials.gov/ct/search?term=NCT00843050 NCT00843050 Purpose The purpose of this study is to determine whether P276-00 is safe and effective in treatment of Mantle Cell Lymphoma that is recurred after or not responding to at least one previous line of treatment. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Age =18 years - Histological diagnosis of MCL and presence of either nuclear Cyclin D1 positivity by immunohistochemistry or t(11;14) by fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR), or conventional karyotyping - Documented progression or relapse after at least 1 line of prior chemotherapy - Presence of measurable disease - ECOG performance status 0, 1, or 2 - Life expectancy of at least 3 months - Ability to understand and the willingness to sign a written informed consent document (ICD) - Full recovery from all prior treatment toxicities of Common Terminology Criteria for Adverse Events (CTCAE) Grade = 1 Other eligibility criteria may apply. - Prior radiation therapy, chemotherapy or biologic/targeted anticancer agents within 4 weeks of study drug administration - Prior treatment with monoclonal antibodies or any radio- or toxin- immunoconjugates within 3 months of study drug administration; however, a patient who has had rituximab treatment within 3 months and has had PD after such treatment is allowed in the study. - Prior allogeneic stem cell transplantation within 1 year of study drug administration - Current or prior CNS lymphoma - QTc > 450 msec - Unstable angina, myocardial infarction, CHF or stroke within previous 6 months of study drug administration - Presence of active and serious comorbidity and uncontrolled illness other than MCL - History of other prior malignancies except for properly treated basal cell or squamous cell carcinoma of skin, in situ cervical cancer, in situ breast cancer or early stage prostate cancer - Hemoglobin <8.0 gm/dL - Absolute neutrophil count <1000/mm3 - Platelet count <50,000/mm3 - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >3 × institutional upper limit of normal (ULN) (> 5 × institutional ULN if liver is involved with lymphoma or if patient has Gilbert's Disease) - Total bilirubin, >1.5 × institutional ULN (> 3 × institutional ULN if liver is involved with lymphoma or if patient has Gilbert's Disease) - Serum creatinine >1.5 × institutional ULN - Patients known to be suffering from infection with human immunodeficiency virus (HIV), tuberculosis, Hepatitis C or Hepatitis B - Pregnant or lactating women - Women of childbearing potential or men not willing to use at least 2 approved methods of contraception (one of which being a barrier method) after signing the ICD, during the entire study and for at least 4 weeks following withdrawal from the study Other exclusion criteria may apply. 38f297e664d5ac8e8272d4002af31bcb 8041 An SGN-35 Trial for Patients Who Have Previously Participated in an SGN-35 Study II Ajay Gopal, MD 20091827 36 Hematologic Malignancies Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8041.html http://www.clinicaltrials.gov/ct/search?term=NCT00947856 NCT00947856 Purpose This is a multicenter, open-label study to evaluate the safety and efficacy of treatment with SGN-35 in patients who have previously participated in an SGN-35 study. Ages Eligible for Study: 12 Years and older Genders Eligible for Study: Both - Participated in a previous SGN-35 study. - CD30-positive hematologic malignancy. - At a minimum, experienced clinical benefit in the prior SGN-35 study. Other eligibility criteria may apply. - Withdrew consent to participate in any prior SGN-35 study Other exclusion criteria may apply. 0ef020af83be106184e99c5e1a4bf281 8006 Dose Escalation Study of MLN4924 in Adults With Melanoma I Shailender Bhatia, MD 20091841 52; 83 Melanoma; Solid Tumors Phase 1 Program, Study Line phase1@u.washington.edu 206/288-7551 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8006.html http://www.clinicaltrials.gov/ct/search?term=NCT01011530 NCT01011530 Purpose This is an open-label, multicenter, phase 1, dose escalation study that will evaluate the safety profile, establish Maximum Tolerated Dose (MTD), and inform the recommended phase 2 dose of MLN4924 as well as evaluate antitumor activity in patients with metastatic melanoma. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both Each patient must meet all of the following criteria to be enrolled in the study: - Diagnosis of metastatic melanoma - Measurable disease. - Female patients who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or abstain from heterosexual intercourse. - Male patients who agree to practice effective barrier contraception or agree to abstain from heterosexual intercourse. - Willing and able to give written informed consent. - Suitable venous access for study-required blood sampling. - Appropriate functional status, including the recovery from the effects of prior antineoplastic therapy, and acceptable organ function as described in the protocol. Other eligibility criteria may apply. Patients meeting any of the following exclusion criteria are not to be enrolled in the study: - Major surgery or, serious infections, or infections that required systematic antibiotic therapy within 14 days before the first dose of study drug. - Systemic antineoplastic or radiation therapy within 14 days or treatment with any investigational products within 21 days before the first dose of study treatment. - CYP3A inducers within 14 days of study treatment. Moderate and strong CYP3A inhibitors and CYP3A inducers are not permitted during the study. - Diarrhea that is greater than Grade 1 as outlined in the protocol - Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure, angina, or myocardial infarction within the past 6 months. - Known human immunodeficiency virus (HIV) positive, hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection. - Serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to the protocol. - Other clinical and laboratory assessments that do not meet the criteria specified in the protocol. Other exclusion criteria may apply. 5fac02cec7ab4f39cd9b15c294081308 7775 Study of Plerixafor Combined With Cytarabine and Daunorubicin in Patients With Newly Diagnosed Acute Myeloid Leukemia I Pamela Becker, MD, PhD 20091942 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.7775.html http://www.clinicaltrials.gov/ct/search?term=NCT00990054 NCT00990054 Purpose The purpose of this research study is to determine if plerixafor can make cells more sensitive to killing by Cytarabine and Daunorubicin, an anti-cancer drug regimen referred to as "7+3" that is commonly used in treating acute myeloid leukemia (AML). In this study, plerixafor will be added to treatment with Cytarabine and Daunorubicin. Subjects will be monitored to see how well they tolerate the use of these drugs together and how well they work to treat the leukemia. The purpose of the study is to find the highest dose of plerixafor and/or recommended phase 2 dose that can be given safely with Cytarabine and Daunorubicin. Ages Eligible for Study: 18 Years to 70 Years Genders Eligible for Study: Both - Provide signed, dated informed consent prior to any protocol-specific procedures. - Have a diagnosis of Newly Diagnosed AML, defined as >20% myeloblasts on the marrow aspirate or peripheral blood differential, with or without extramedullary involvement, with confirmatory immunophenotyping or immunocytochemistry (e.g., myeloperoxidase), documented within 14 days of enrollment. - Have Eastern Cooperative Oncology Group (ECOG) performance status (Appendix A) score of 0, 1, or 2. - Toxicities from all prior treatments have resolved to baseline or d Grade 1 prior to first dose of study drugs. - Are surgically or biologically sterile or willing to practice acceptable birth control, as follows: Females of child bearing potential must agree to abstain from sexual activity or to use a medically approved contraceptive measure/regimen during and for 3 months after the treatment period. Women of child bearing potential must have a negative serum pregnancy test at the time of enrollment. Acceptable methods of birth control include oral contraceptive, intrauterine device (IUD), transdermal/implanted or injected contraceptives and abstinence. - Males must agree to abstain from sexual activity or agree to utilize a medially-approved contraception method during and for 3 months after the treatment period. - Have adequate renal and hepatic function, as indicated by the following laboratory values: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) d2.5 - upper limit of normal (ULN); Estimated creatinine clearance (CrCl) of > 50mL/min, as calculated by the Cockcroft-Gault equation (Appendix F); total bilirubin =1.5-ULN (except in patients with Gilbert Syndrome, in whom direct bilirubin must be =1.5-ULN), International Normalized Ratio (INR) =1.5 after discontinuation of anticoagulants. - Have adequate cardiac function, as measured by left ventricular ejection fraction (LVEF) =40% on echocardiography or multigated acquisition (MUGA) scan or similar radionuclide angiographic scan. - Be able to comply with study procedures and follow-up examinations. Other eligibility criteria may apply. - Have received previous systemic treatment for leukemia or antecedent hematologic disorder (AHD), other than hydroxyurea or hematopoietic growth factors. Treatment with hydroxyurea within 2 weeks of screening is allowed but must be discontinued at least 24 hours prior to the first dose of study drugs.. - Have received prior treatment with plerixafor, cytarabine, or any anthracycline. - Have a diagnosis of acute promyelocytic leukemia (APL), French-American-British (FAB) classification M3 or World Health Organization (WHO) classification of APL with t(15;17)(q(22;q12), or Bcr-Abl positive leukemia. - Have a diagnosis of AML following an AHD (myelodysplasia or myeloproliferation ) of e2 months duration and/or AML secondary to exposure to chemotherapy or radiation. - For patients < 50 years of age, have cytogenetics associated with good prognosis [(t(8;21)q(22;22), t(15;17),inv(16)(p13;q22)]. (Testing for these mutations must be performed on blood or Bone Marrow prior to study registration. - Have had a hematopoietic stem cell transplant (HSCT). - Have an absolute blast count of > 50,000/per microliter at the time of first dose of chemotherapy, despite cytoreduction with hydroxyurea or leukapheresis. - Have central nervous system (CNS) leukemia (Only patients with suspected CNS leukemia must undergo lumbar puncture.) - Have any of the following within the last 12 months: unstable supraventricular arrhythmia (e.g., hemodynamic instability) or has a pacemaker; Any ventricular arrhythmia, other than occasional premature ventricular contractions; Congestive heart failure (controlled or uncontrolled); Myocardial infarction, ischemia, stable coronary artery disease, or angina; Uncontrolled hypertension; Syncope with either a known cardiovascular or an unknown etiology. - Have a pre-existing disorder predisposing the patient to serious or life-threatening infection (e.g., cystic fibrosis, congenital or acquired immunodeficiency, bleeding disorder, or cytopenias). - Have the need for anticoagulant therapy. - Have a significant medical or psychiatric disorder that would interfere with consent, study participation, or follow-up. - Have an active acute or chronic systemic fungal, bacterial, viral, or other infection (i.e., exhibiting ongoing signs/symptoms related to the infection [except isolated fever] and without improvement, despite appropriate antibiotics or other treatment). - Have severe concurrent diseases (e.g., a history of serious organ dysfunction or disease) that may place the patient at undue risk to undergo induction therapy per protocol, or obscure assessments of drug safety. - Have a diagnosis of prior malignancy unless disease-free for at least 5 years following therapy with curative intent, with the following exceptions: patients with treated nonmelanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, regardless of the disease-free duration, if definitive treatment for the condition has been completed; or patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen (PSA) values after treatment with curative intent. - Have known human immunodeficiency virus (HIV) positivity or evidence of active viral hepatitis. - Are pregnant or breastfeeding. Other exclusion criteria may apply. 57245f530149da97a1eb8ed80abd48d4 7982 A Study of ABT-888 in Combination With Carboplatin and Gemcitabine in Subjects With Advanced Solid Tumors I Heidi Gray, MD 20091988 83 Solid Tumors Phase 1 Program, Study Line phase1@u.washington.edu 206/288-7551 http://www.fhcrc.org/en/treatment/clinical-trials/detail.7982.html http://www.clinicaltrials.gov/ct/search?term=NCT01063816 NCT01063816 Purpose The purpose of this study is to determine the maximum tolerated dose and establish the recommended Phase 2 dose of ABT-888 when administered in combination with carboplatin and gemcitabine in subjects with advanced solid tumors. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Histologically confirmed solid tumors that are metastatic or unresectable for which carboplatin/gemcitabine is a treatment option. - Eastern Cooperative Group performance score of 0 to 2. - Adequate hematologic, hepatic and renal function. Other eligibility criteria may apply. - Subject has received any anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, biologic or any investigational therapy within 28 days prior to study administration. - Subjects with known history of brain metastases and primary CNS tumors. - Hypertensive reaction to carboplatin or gemcitabine. Other exclusion criteria may apply. dcac1d98af2508662444a4c431f6211c 7812 Phase III Trans-Arterial Chemo-Embolization (TACE) Adjuvant HCC (BRISK TA) III Edward Lin, MD 20092129 28; 45; 83 Gastrointestinal Cancer; 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.7812.html http://www.clinicaltrials.gov/ct/search?term=NCT00908752 NCT00908752 Purpose The purpose of this study is to compare the Overall Survival (OS) of HCC patients who receive brivanib as adjuvant treatments to TACE therapy, with the OS of HCC patients who receive matched placebo with TACE therapy. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Patients with diagnosis of hepatocellular carcinoma - Cirrhotic status of Child-Pugh Class A or B with a score of 7 - ECOG performance status of 0 or 1 - Adequate hematologic, hepatic, and renal function Other eligibility criteria may apply. - Prior use of any systemic anticancer chemotherapy, immunotherapy, investigational or - molecular targeted agents for HCC - History of cardiac disease - Active and untreated hepatitis B - Inability to swallow tablets or untreated malabsorption syndrome - History of human immunodeficiency virus (HIV) infection Other exclusion criteria may apply. e77eedde02080dd40d95378f66b14a00 8152 MLN8237 in Patients With Ovarian, Fallopian Tube or Peritoneal Cancer Preceded by Phase 1 Study of MLN8237 Plus Paclitaxel Treatment of Ovary or Breast Cancer I/II Barbara Ann Goff, MD 20100202 25; 34; 65; 83; 125 Fallopian Cancer; Gynecological Cancer; Ovarian Cancer; Solid Tumors; Primary Peritoneal Cancer (PPC) Phase 1 Program, Study Line phase1@u.washington.edu 206/288-7551 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8152.html http://www.clinicaltrials.gov/ct/search?term=NCT01091428 NCT01091428 Purpose This is an open-label, multicenter study with a nonrandomized Phase 1 portion and an open-label, randomized, Phase 2 portion evaluating MLN8237 in combination with weekly paclitaxel in adult female patients with advanced breast cancer (Phase 1 portion only) and recurrent ovarian cancer (both Phase 1 and Phase 2 portions). Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Female Each patient must meet all of the following inclusion criteria to be enrolled in the study: - Female patients 18 years or older - Previously treated, metastatic or locally recurrent malignancy with 1 of the following diagnoses, which has been confirmed histologically or cytologically: adenocarcinoma of the breast (Phase 1 only), recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma (Phase 1 and 2). - Patients with breast cancer must have received treatment with at least 1 but no more than 4 prior chemotherapy regimens not including regimens received in the neoadjuvant and/or adjuvant setting - Patients with breast cancer must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 - No antineoplastic therapy or radiotherapy within 3 weeks before enrollment (2 weeks for regimens with recovery expected within 7 to 14 days) and recovered from toxicities of prior therapy (except alopecia); the patient must have recovered from all treatment-related toxicities and must have evidence of PD or persistent disease - Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 - Adequate bone marrow, liver and renal function, and serum albumin > lower limit of normal (LLN) - Postmenopausal at least 1 year, OR Surgically sterile, OR If childbearing potential, agree to 2 effective methods of nonhormonal contraception, or agree to completely abstain from heterosexual intercourse - Able to provide written informed consent - Willing to comply with scheduled visits, treatment plan, laboratory tests and other trial procedures - Suitable venous access Specific Inclusion Criteria for Patients with Recurrent Ovarian, Fallopian Tube or Peritoneal Cancer: - Prior treatments must have included a platinum and a taxane (not a weekly taxane regimen). Disease must have recurred = 12 months after discontinuation of platinum therapy. - Measurable disease in target lesions or assessable disease (defined by CA-125 per protocol) - Disease that has progressed per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or modified Gynecologic Cancer Intergroup (GCIG) CA-125 criteria Other eligibility criteria may apply. Patients meeting any of the following exclusion criteria are not to be enrolled in the study: - Prior treatment with an Aurora A-targeted agent or a weekly taxane regimen - Treatment with more than 4 cytotoxic chemotherapy regimens in the metastatic setting; prior therapy cannot include more than 2 prior taxane-containing regimens and cannot include a prior weekly taxane regimen - Current use of tamoxifen, thalidomide or any agent used as maintenance or consolidation therapy for Ovarian Cancer - Known hypersensitivity to Cremophor® EL, paclitaxel or its components - Prior history of = Grade 2 neurotoxicity or any toxicity requiring discontinuation from taxane chemotherapy that is not resolved to = Grade 1 - Comorbid or unresolved toxicity that would preclude administration of weekly paclitaxel - Primary central nervous system malignancy or carcinomatous meningitis - Symptomatic brain metastasis - Inability to swallow oral medications or maintain a fast - History of hemorrhagic or thrombotic cerebrovascular event in past 12 months - Surgery within 3 weeks before study enrollment and not fully recovered - Diagnosis or treatment of another malignancy within 2 years preceding first dose of MLN8237 and have any evidence of residual disease except nonmelanoma skin cancer or in situ malignancy completely resected - Pregnant or lactating - Serious illness that could interfere with protocol completion - Investigational treatment 21 days prior to first dose of MLN8237 - Prior allogeneic bone marrow or organ transplantation - Infection requiring systemic antibiotic therapy within 14 days prior to first dose of MLN8237 - Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C - Radiotherapy to > 25% bone marrow or whole pelvic radiotherapy Other exclusion criteria may apply. 9a3e6a61962f9558b4fdcb9832f63379 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 8325 Study of Palifosfamide-tris in Combination With Doxorubicin in Patients With Front-line Metastatic Soft Tissue Sarcoma (PICASSO III) III Eve Rodler, MD 20100687 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.8325.html http://www.clinicaltrials.gov/ct/search?term=NCT01168791 NCT01168791 Purpose This is an international, randomized, double-blind, placebo-controlled trial to evaluate the clinical efficacy of palifosfamide-tris administered with doxorubicin in combination, compared with doxorubicin administered with placebo in front-line patients diagnosed with metastatic soft tissue sarcoma (STS). Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both To be eligible, each patient must meet EACH of the following criteria: - Age =18 years. - Documented soft tissue sarcoma - Metastatic disease for which the patient has not received any prior treatment, and for whom treatment with doxorubicin is considered medically acceptable. - ECOG Performance Status of 0, 1 or 2 - Adequate bone marrow and organ function based on the results of protocol- specified laboratory tests - Male and female patients must agree to use a highly reliable method of birth control during study participation. - Able to provide informed consent - To be eligible, each patient must meet NONE of the following criteria: - Specific sarcoma histological subtypes including GIST and Ewing's sarcoma. - Systemic therapy for the treatment of metastatic sarcoma, prior to or during the study. However, patients may have received neo-adjuvant/adjuvant Gemzar and Taxotere chemotherapy for their primary sarcoma, prior to the development of metastatic disease - Any prior anthracycline use. - Known allergy to any of the study drugs or their excipients. - Any unstable or clinically significant concurrent medical condition that would, in the opinion of the investigator, jeopardize the safety of a patient and/or their compliance with the protocol, based on screening tests, physical examination and medical history (as specifically defined in the clinical protocol). - Myocardial dysfunction defined as left ventricular ejection fraction (LVEF) <50%. - Documented metastases to brain or meninges. - Any malignancy other than sarcoma within the last 5 years prior to screening, with the exception of cervical carcinoma in situ, basal cell carcinoma, or superficial bladder tumors (Ta, Tis, or T1) that have been successfully and curatively treated with no evidence of recurrent or residual disease. - Currently pregnant or nursing. - Radiotherapy with curative intent within 4 weeks of first dose of study drug. Other eligibility criteria may apply. To be eligible, each patient must meet NONE of the following criteria: - Specific sarcoma histological subtypes including GIST and Ewing's sarcoma. - Systemic therapy for the treatment of metastatic sarcoma, prior to or during the study. However, patients may have received neo-adjuvant/adjuvant Gemzar and Taxotere chemotherapy for their primary sarcoma, prior to the development of metastatic disease - Any prior anthracycline use. - Known allergy to any of the study drugs or their excipients. - Any unstable or clinically significant concurrent medical condition that would, in the opinion of the investigator, jeopardize the safety of a patient and/or their compliance with the protocol, based on screening tests, physical examination and medical history (as specifically defined in the clinical protocol). - Myocardial dysfunction defined as left ventricular ejection fraction (LVEF) <50%. - Documented metastases to brain or meninges. - Any malignancy other than sarcoma within the last 5 years prior to screening, with the exception of cervical carcinoma in situ, basal cell carcinoma, or superficial bladder tumors (Ta, Tis, or T1) that have been successfully and curatively treated with no evidence of recurrent or residual disease. - Currently pregnant or nursing. - Radiotherapy with curative intent within 4 weeks of first dose of study drug. Other exclusion criteria may apply. fe10d55e8c5abcf37dac403b6ba782a0 8320 A Study for Patients With Recurrent or Metastatic Squamous Cell Head and Neck Cancer II Laura Chow 20100688 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.8320.html http://www.clinicaltrials.gov/ct/search?term=NCT01087970 NCT01087970 Purpose The purpose of this study is to look for an improvement in progression free survival with the combination of pemetrexed, carboplatin (or cisplatin) and cetuximab in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both -Histologic or cytologic diagnosis of squamous cell head and neck cancer: 1) Recurrent disease (locally advanced or metastatic)that is not amenable to local therapy, (i) with at least 6 months since completion of systemic therapy (chemotherapy or biological anticancer therapy), and (ii) with no more than 1 prior multimodal therapy (such as concurrent chemoradiation with or without sequential chemotherapy) for locally advanced HNC tumor, and (iii) with no prior systemic therapy (chemotherapy or biological anticancer therapy) for metastatic disease; OR 2) Newly diagnosed distant metastatic disease (Stage IVc) -Prior therapies: 1) Radiation therapy must be completed at least 4 weeks before study enrollment. For palliative therapy, prior radiation therapy allowed <25% of the bone marrow and prior radiation to the whole pelvis is not allowed. Patients must have recovered from the acute toxic effects of the treatment prior to study enrollment. 2) Surgery (excluding prior diagnostic biopsy) must be completed at least 4 weeks before study enrollment. Patients must have fully recovered from any acute effects of surgery prior to study enrollment. - An estimated life expectancy of at least 12 weeks. - Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. - Biological tissue available for biomarker analysis on tumor tissue. - Disease status must be measurable as defined by RECIST. The index lesion must not be In a prior irradiated area. Positron emission tomography (PET) scans and ultrasounds may not be used for lesion measurements. - Patient compliance and geographic proximity that allow for adequate follow-up. - Adequate organ function as defined by the following: 1) Bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) greater than or equal to 1.5 × 109/L, platelets greater than or equal to 100 × 109/L, and hemoglobin greater than or equal to 9 g/dL. 2) Hepatic: bilirubin less than or equal to 1.5 × the upper limit of normal (ULN); alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) less than or equal to 3.0 × ULN (ALP, AST, and ALT less than or equal to 5.0 × ULN is acceptable if the liver has tumor involvement). 3) Renal: calculated creatinine clearance (CrCl) greater than or equal to 60 mL/min. - For women: Must be surgically sterile, postmenopausal, or compliant with a medically approved contraceptive regimen during and for 6 months after the treatment period; must have a negative serum or urine pregnancy test within 7 days before study enrollment, and must not be breast-feeding. For men: Must be surgically sterile or compliant with a contraceptive regimen during and for 6 months after the treatment period. Other eligibility criteria may apply. - Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry. - Are receiving concurrent chronic systemic immune therapy, or chemotherapy for a disease other than cancer. - Concurrent administration of any other antitumor therapy. - Known prior allergic/hypersensitivity reaction to any of the components of the study treatment. - Serious concomitant systemic disorder (for example, active infection) or psychiatric disorder that, in the opinion of the investigator, would compromise the patient's ability to complete the study. - Have serious cardiac disease, such as symptomatic angina, unstable angina, or the history of myocardial infarction in the previous 12 months. - Second primary malignancy that is clinically detectable at the time of consideration for study enrollment. - Have had another primary malignancy other than HNC, unless that prior malignancy was treated at least 2 years previously with no evidence of recurrence. Exception: Patients with a history of in situ carcinoma of the cervix, nonmelanoma skin cancer, or low-grade (Gleason score less than or equal to 6) localized prostate cancer will be eligible even if diagnosed and treated less than 2 years previously. - Nasopharyngeal, paranasal sinus, lip, or salivary gland cancer. - Presence of clinically significant (by physical exam) third-space fluid collections; for example, ascites or pleural effusions that cannot be controlled by drainage or other procedures prior to study entry. - Have peripheral neuropathy of Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or higher. - Have central nervous system (CNS) metastases (unless the patient has completed successful local therapy for CNS metastases and has been off corticosteroids for at least 4 weeks before starting study therapy). Brain imaging is required in symptomatic patients to rule out brain metastases, but is not required in asymptomatic patients. - Inability to interrupt aspirin or other nonsteroidal anti-inflammatory agents, other than an aspirin dose less than or equal to 1.3 grams per day, for a 5-day period (8-day period for long-acting agents, such as piroxicam). - Unable or unwilling to take folic acid, vitamin B12, or prophylactic corticosteroids. - Recent (within 30 days before enrollment) or concurrent yellow fever vaccination. Other exclusion criteria may apply. 28a4f76b804d311c9d5e74ff0055907c 8347 A Phase 1 Dose Escalation Trial of ASG-5ME in Pancreatic Adenocarcinoma I Andrew Coveler, MD 20100718 28; 66; 83 Gastrointestinal Cancer; Pancreatic Cancer; Solid Tumors Phase 1 Program, Study Line phase1@u.washington.edu 206/288-7551 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8347.html http://www.clinicaltrials.gov/ct/search?term=NCT01166490 NCT01166490 Purpose This is a phase 1, open-label, dose-escalation clinical trial to evaluate the safety and tolerability of ASG-5ME and to identify the maximum tolerated dose in patients with pathologically confirmed metastatic pancreatic adenocarcinoma. Ages Eligible for Study: 18 Years to 75 Years Genders Eligible for Study: Both - Pathologically confirmed metastatic pancreatic adenocarcinoma - Measurable disease (at least one nonresectable, non-nodal lesion greater than or equal to 10 mm in longest diameter or nodal lesion greater than or equal to 15 mm in shortest axis) - ECOG performance status of 0 or 1 - May be untreated or have previously received treatment for pancreatic adenocarcinoma. For patients who have previously received treatment, it must be at least 2 weeks since the last systemic therapy or radiation, and at least 4 weeks since treatment with any monoclonal antibody (other than bevacizumab). Other eligibility criteria may apply. - Evidence or history of central nervous system metastases - History of another primary malignancy that has not been in remission for at least 3 years - Documented history of a cerebral vascular event, unstable angina, myocardial infarction, or cardiac symptoms consistent with NYHA Class III-IV within 6 months prior Other exclusion criteria may apply. 0a66956d952e126a4066ac52c50258a1 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 8413 A Safety and Efficacy Study of Oral MDV3100 in Chemotherapy-Naive Patients With Progressive Metastatic Prostate Cancer (PREVAIL) III Tia Higano, MD 20101081 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.8413.html http://www.clinicaltrials.gov/ct/search?term=NCT01212991 NCT01212991 Purpose The purpose of this study is to determine the benefit of MDV3100 versus placebo as assessed by overall survival and progression-free survival in patients with progressive metastatic prostate cancer who have failed androgen deprivation therapy but not yet received chemotherapy. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Male - Histologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features - Ongoing androgen deprivation therapy with a GnRH analogue or bilateral orchiectomy - Progressive disease despite androgen deprivation therapy as defined by rising PSA levels or progressive soft tissue or bony disease - No prior treatment with cytotoxic chemotherapy - Asymptomatic or mildly symptomatic from prostate cancer Other eligibility criteria may apply. - Severe concurrent disease, infection, or co-morbidity that, in the judgment of the Investigator, would make the patient inappropriate for enrollment - Known or suspected brain metastasis or active leptomeningeal disease - History of another malignancy within the previous 5 years other than curatively treated non-melanomatous skin cancer Other exclusion criteria may apply. f63924fe4c607e36a870443c1cec7c0c 8361 Trivalent Ganglioside Vaccine With Immunological Adjuvant or Immunological Adjuvant Alone in Metastatic Sarcoma Patients Who Are Rendered Disease Free II Eve Rodler, MD 20101150 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.8361.html http://www.clinicaltrials.gov/ct/search?term=NCT01141491 NCT01141491 Purpose: Sarcoma patients are at high risk for their cancer to recur even when the sarcoma has been removed surgically or treated with radiation or chemotherapy. The patients in the study will be randomized (like flipping a coin) to receive either a vaccine that is combined with an immune system stimulant or the immune system stimulant alone. The immune system stimulant is called OPT-821 and is an immunological booster. The trivalent vaccine is being developed to teach the patient's immune system to recognize 3 types of sugars called GM2, GD2 and GD3 that are found primarily on the surface of sarcoma cells. If the trivalent vaccine can stimulate the patient's immune system to develop antibodies which recognize and target the GM2, GD2 and GM3 sugars, then the patient's antibodies could attack and kill any remaining sarcoma cells potentially preventing the recurrence of sarcoma. Detailed Description: This study is a Phase II randomized, double-blind, multi-center study of a trivalent ganglioside vaccine plus the immunological adjuvant OPT-821 (Arm A) versus OPT-821 alone (Arm B) for patients with metastatic sarcoma at initial presentation or with relapsed disease who have been rendered disease-free following either surgical resection or multi-modality therapy. The primary aim of this study is to demonstrate the efficacy of vaccine therapy over non-specific immune therapy. Another aim of this study is to obtain sufficient data to further the development of this specific vaccine therapy as well as guide future study designs for therapeutic cancer vaccines in general. To be eligible, patients must have histologically confirmed sarcoma, must be clinically free of disease after surgery or multimodality therapy, and must be within 8 weeks of completion of such therapy. Given the limited data regarding ganglioside expression in Ewing sarcoma, rhabdomyosarcoma, and gastrointestinal stromal tumors, patients with these sarcoma subtypes will be excluded. Patients must have a history of distant metastatic disease; patients with locally recurrent disease only will not be eligible, as these patients demonstrate a different natural history from those with metastatic disease. All treatment will be performed in the outpatient setting. Patients will be randomized in a 1:1 ratio to receive a total of 10 treatments of either the vaccine plus OPT-821 (Arm A) or OPT-821 alone (Arm B). Treatment will be administered on Visit Weeks 1, 2, 3, 8, 16, 28, 40, 52, 68, and 84. All patients will receive 150 mcg of OPT-821. 1. Male or female, 16 years or older. 2. American Joint Committee on Cancer (AJCC) Stage IV sarcoma with no current radiological evidence of residual disease following either surgery alone or multimodality therapy for treatment of metastatic or relapsed disease. Patients must have presented with either newly diagnosed metastatic sarcoma or distant relapsed disease. Non-surgical local ablative therapies such as SRS or cryotherapy cannot replace surgical resection of disease for purpose of eligibility. 3. Histological confirmation of sarcoma, as performed by a pathologist at one of the participating study sites, prior to entry on study. 4. Patients who have undergone surgery must have done so within 8 weeks prior to initiation of treatment on this study. 5. Patients must have completed radiation or systemic chemotherapy at least 4 weeks prior to treatment on this study. 6. Patients previously treated with chemotherapy and/or radiotherapy as part of a multimodality treatment for metastatic disease must have recovered from all adverse effects of treatment or have returned to baseline status. 7. Imaging study performed within 4 weeks prior to administration of first vaccination documenting that patient has no evidence of disease. Study must include CT scan of chest, abdomen, and pelvis. 8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1. 9. Weight = 40 kg. 10. Have organ and marrow function as defined below: WBC = 3.0 cells/mm3 Platelets = 100,000/mm3 Total bilirubin = 2.0 mg/dL AST (SGOT)/ALT (SGPT) = 1.5 x ULN 11. Current use of an acceptable form of birth control. 12. Ability to understand English and to provide written informed consent and authorization for protected health information disclosure whether by self or by legally authorized representative. Other eligibility criteria may apply. 1. Patients who develop locally recurrent disease only with no evidence of distant metastatic disease at the time of relapse. 2. Evidence of local or metastatic disease or who are not disease free at the time of the first vaccination. 3. Patients with Ewing sarcoma, rhabdomyosarcoma, or gastrointestinal stromal tumors. 4. Patients previously treated with KLH or ganglioside containing vaccines or monoclonal antibodies (mAbs) against gangliosides. 5. Females of childbearing potential that are pregnant or intend to become pregnant or who are breastfeeding. Females must have negative ßHCG test within two weeks of first vaccination. 6. Current active malignancy or history of malignancy, other than sarcoma, within the past two years, except for cervical carcinoma in situ, basal cell carcinoma, or squamous cell carcinoma that has been surgically removed or prostate cancer that is being managed by watchful waiting. 7. Any medical condition that may limit the ability of the patient to complete the full course of treatment or to respond immunologically to vaccination, (including autoimmune or neurodegenerative disorders such as multiple sclerosis and amyotrophic lateral sclerosis). 8. Patients requiring repeated or continuous doses of anti-inflammatory medications (steroids, non-steroidal anti-inflammatory drugs, or full dose aspirin). Episodic use of steroids or non-steroidal anti-inflammatory drugs permitted as long as they are not given within one week prior to or following vaccine administration. Continuous dosing of low-dose aspirin (= 81 mg/day) is acceptable. 9. Use of or treatment with a drug that has not received regulatory approval or participation in a drug or device study during the 28 days preceding the first vaccination. 10. Known history of HIV-positivity OR serologic evidence of HIV at screening or any other immunodeficiency disorders or illnesses. Serologic positivity for the Hepatitis B Virus (HBV) or the Hepatitis C Virus (HCV), unless explained by a documented vaccination. 11. Inability or unwillingness to meet the attendance requirements of the study. 12. Any clinically significant abnormal finding at Screening (as determined by the Principal Investigator, in consultation with the Medical Monitor and the Sponsor), that would interfere with study participation, that would interfere with the evaluation or quality of the data, or that would put the patient at increased risk of illness or injury. Other exclusion criteria may apply. 5b47040a3e12e9efbd0c27e8fef3a429 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 8461 A Study of TRU-016 in Combination With Rituximab and Bendamustine in Subjects With Relapsed Indolent Lymphoma I Ajay Gopal, MD 20101336 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.8461.html http://www.clinicaltrials.gov/ct/search?term=NCT01317901 NCT01317901 Purpose This is a Phase 1b/2 multicenter, open-label study of bendamustine, rituximab and TRU-016 (BRT) in up to approximately 88 subjects with relapsed indolent B-cell lymphoma. The study will be conducted in 2 parts, Phase 1b and Phase 2. Phase 1b is an open-label, non-randomized, multiple-dose escalation study to determine the MTD of TRU-016 given in combination with rituximab and bendamustine and to determine a safe dosing regimen for the combination in up to 12 subjects with relapsed indolent lymphoma. The Phase 2 portion is an open-label, randomized study to evaluate the efficacy of BRT compared with BR. Approximately 76 subjects will be randomized in a 1:1 ratio to one of the 2 treatment groups. The dose level of TRU-016 for Phase 2 will be selected on the basis of safety data after 2 cycles of treatment in Phase 1b. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both Histologically confirmed diagnosis of indolent non-Hodgkin's B-cell lymphoma (ie, follicular lymphoma, small lymphocytic lymphoma, and marginal zone lymphoma) that has relapsed (relapsed is defined as confirmed progressive disease [PD] after receiving the most recent prior therapy, or failure to achieve at least a PR while receiving the most recent prior therapy) At least one prior line of therapy for indolent lymphoma Bi-dimensionally measurable disease with at least one lesion measuring >=1.5 cm in a single dimension Eastern Cooperative Oncology Group (ECOG) performance status of <= 2 Creatinine clearance of >40 mL/min as calculated by the Cockcroft-Gault method as follows: (140 - age) * (weight in kg [* 0.85 if female] / 72 * serum creatinine level) 7. Adequate hepatic function, indicated as follows: - aspartate aminotransferase (AST) of <2.5 x upper limit of normal (ULN) - alanine aminotransferase (ALT) of <2.5 x ULN - total bilirubin of <= 1.5 x ULN 8. Absolute neutrophil count (ANC) >=1000/mm3 (1000/µL) 9. Platelet count >= 100,000/mm3 10. Female subjects of child-bearing potential and male subjects must use an acceptable form of birth control for the duration of their study participation and for 6 months after completing study drug dosing; acceptable forms of birth control, unless dictated otherwise by local regulatory authorities 11. For women of childbearing potential, a negative serum pregnancy test result obtained during the screening period and a negative urine pregnancy test result within 24 hours before first administration of study drug 12. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information Other eligibility criteria may apply. 1. Diagnosis of grade 3b follicular lymphoma or transformed lymphoma of any grade 2. Previously received TRU-016 3. Prior treatment with rituximab if subject discontinued rituximab due to unresolved toxicity 4. Refractory to bendamustine, defined as follows: - progression within 6 months of last dose of bendamustine - failed to achieve at least a PR while receiving bendamustine - discontinued bendamustine due to toxicity - received bendamustine within 6 months prior to first dose of study drug 5. Received chemotherapy, radiotherapy, or immunotherapy including investigational agents within 28 days prior to the first dose of study drug 6. Received therapeutic corticosteroids at doses equivalent to >10 mg prednisone per day for longer than 5 days within 14 days prior to the first dose of study drug, except if needed as a pre-medication 7. Received filgrastim or equivalent within 14 days prior to screening (ie, collection of samples for laboratory tests) or pegfilgrastim within 28 days prior to screening (ie, collection of samples for laboratory tests) 8. Prior allogeneic bone marrow transplant 9. Prior autologous bone marrow transplant within 12 months prior to the first dose of study drug 10. Received blood or platelet infusion within 7 days prior to screening (ie, collection of samples for laboratory tests) 11. Previous or concurrent additional malignancy except non-invasive, non-melanomatous skin cancer or in situ carcinoma of the cervix, or other solid tumors if the subject has been disease-free for a minimum of 2 years prior to the first dose of study drug 12. Known central nervous system or leptomeningeal lymphoma 13. Any significant concurrent medical diseases or conditions, including but not limited to the following: - Clinically significant pulmonary dysfunction requiring oxygen therapy - An active infection (viral, bacterial, or fungal) requiring systemic therapy; subjects receiving prophylactic therapy are eligible 14. Known allergy to mannitol 15. History of positive serology for human immunodeficiency virus (HIV) 16. Positive serology for hepatitis B (surface antigen or core antibody) Note: If a positive test result for hepatitis B core antibody is due to immunoglobulin treatment, the subject may be enrolled if the hepatitis B viral deoxyribonucleic acid (DNA) is negative. 17. Positive serology for hepatitis C 18. Pregnant or breastfeeding 19. Other severe, acute, or chronic medical or psychiatric condition, laboratory abnormality, or difficulty complying with protocol requirements that may increase the risk associated with study participation or study drug administration or may interfere with safety 20. Any condition that, in the investigator's opinion, makes the subject unsuitable for study participation Other exclusion criteria may apply. 076ec5773022d3342566ce28a749ace0 8567 A Study of Paclitaxel With or Without Ramucirumab in Metastatic Gastric Adenocarcinoma (RAINBOW) III Edward Lin, MD 20101546 27; 28; 83; 84 Gastric Cancer; Gastrointestinal Cancer; Solid Tumors; Stomach Cancer Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8567.html http://www.clinicaltrials.gov/ct/search?term=NCT01170663 NCT01170663 Purpose This is a phase III randomized multicenter double-blind, placebo controlled trial evaluating the safety and efficacy of paclitaxel plus ramucirumab drug product (DP) compared to paclitaxel plus placebo. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Signed informed consent histologically or cytologically confirmed gastric or gastroesophageal junction adenocarcinoma - Metastatic disease or locally advanced, unresectable disease - Disease progression during or within 4 months after the last dose of the first-line therapy (platinum/fluoropyrimidine doublet with or without anthracycline) - Organs are functioning well (liver, kidney, blood) - Good performance status (ECOG 0 to 1) Other eligibility criteria may apply. - First line chemotherapy for metastatic gastric cancer other than platinum/fluoropyrimidine doublet with or without anthracycline - Previous systemic therapy with other anti-angiogenic drugs - Uncontrolled high blood pressure - Symptomatic or poorly controlled heart disease or had a heart attack or stroke within the last 6 month - Evidence of CNS metastasis at baseline Other exclusion criteria may apply. 5ec7d57b26d5f2a92a939de6a6148d0e 8556 A Phase 1 Study of Brentuximab Vedotin Given Sequentially and Combined With Multi-Agent Chemotherapy for Anaplastic Large Cell Lymphoma I Andrei Shustov, MD 20101576 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.8556.html http://www.clinicaltrials.gov/ct/search?term=NCT01309789 NCT01309789 Purpose The purpose of this study is to assess the safety profile of brentuximab vedotin sequentially and in combination with multi-agent chemotherapy in front-line treatment for systemic anaplastic large cell lymphoma. It is a phase 1, open-label, dose escalation study in three arms designed to define the MTD, PK, immunogenicity, and anti-tumor activity of brentuximab vedotin in sequence and in combination with multi-agent front-line chemotherapy. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Treatment-naive systemic anaplastic large cell lymphoma - Measurable disease of at least 1.5 cm - ECOG performance status less than or equal to 2 Other eligibility criteria may apply. - Known cerebral/meningeal disease - Current diagnosis of primary cutaneous anaplastic large cell lymphoma - History of another primary malignancy that has not been in remission for at least 3 years - Left ventricular ejection fraction <45% or symptomatic cardiac disease, or myocardial infarction within the past 12 months - Viral, bacterial, or fungal infection within two weeks prior to the first dose of brentuximab vedotin - Known human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus positive status Other exclusion criteria may apply. 4a599f121973f7201ef8d6b0439f4a5f 8762 Study of Zalypsis® (PM00104) in Patients With Unresectable Locally Advanced and/or Metastatic Ewing Family of Tumors (EFT) Progressing After at Least One Prior Line of Chemotherapy II Robin Jones 20101618 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.8762.html http://www.clinicaltrials.gov/ct/search?term=NCT01222767 NCT01222767 Purpose This is a phase II Multicenter, Open-label, Clinical and Pharmacokinetic Study of Zalypsis® (PM00104) in Patients with Unresectable Locally Advanced and/or Metastatic Ewing Family of Tumors (EFT) Progressing After at Least One Prior Line of Chemotherapy to determine the antitumor activity of Zalypsis. Ages Eligible for Study: 16 Years and older Genders Eligible for Study: Both Voluntary written informed consent, obtained from the patient or his/her representative before the beginning of any specific study procedures. Age = 16 years. Histologically or cytologically confirmed EFT (Ewing Family of Tumors), with recurrent disease. Documented failure to at least one prior chemotherapy regimen for their disease. Radiographic documentation of disease progression at study entry. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score = 2. Life expectancy = 3 months. Complete recovery from the effects of drug-related adverse events (AEs) derived from previous treatments, excluding alopecia and grade 1 peripheral neuropathy, according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v. 4.0. At least one measurable lesion ("target lesion" according to the RECIST v.1.1), located in a non-irradiated area and adequately measured less than four weeks before study entry. Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is clearly documented or biopsy proven. Absolute neutrophil count (ANC) = 1.5 x 109/l; platelet count = 100 x 109/l, and hemoglobin = 9 g/dl. Adequate renal function: calculated creatinine clearance (using Cockcroft and Gault's formula) = 30 ml/min. Adequate hepatic function: - Total bilirubin = 1.5 x upper limit or normality (ULN), unless due to Gilbert's syndrome. - Alanine aminotransferase (ALT), aspartate aminotransferase (AST) = 3 x ULN (= 5 x ULN in case of hepatic metastases), and alkaline phosphatase (AP) = 2.5 x ULN (= 5 x ULN in case of extensive bone involvement). - Albumin = 25 g/l. Left ventricular ejection fraction (LVEF) within normal limits (LVEF of at least 50%). Women of childbearing potential must have a negative serum pregnancy test before study entry. Both women and men must agree to use a medically acceptable method of contraception throughout the treatment period and for three months after discontinuation of treatment. Acceptable methods of contraception include complete abstinence, intrauterine device (IUD), oral contraceptive, subdermal implant and double barrier (condom with a contraceptive sponge or contraceptive suppository). Other eligibility criteria may apply. Prior therapy with Zalypsis®. Pregnant or lactating women or women of childbearing potential not using an appropriate contraceptive method. Less than three weeks from prior radiation therapy, biological therapy or chemotherapy. Less than six weeks from prior nitrosourea, mitomycin C, high-dose chemotherapy or radiotherapy involving the whole pelvis or over 50% of the spine, provided that acute effects of radiation treatment have resolved. Hormonal therapy and palliative radiation therapy (i.e., for control of pain from bone metastases) must be discontinued before study entry. Patients with a prior invasive malignancy (except non-melanoma skin cancer and in situ cervix carcinoma) who have had any evidence of disease within the last five years or whose prior malignancy treatment contraindicates the current protocol therapy. Evidence of progressive or symptomatic central nervous system (CNS) metastases or leptomeningeal metastases. Other diseases or serious conditions: A. Increased cardiac risk, as defined by: - Unstable angina or myocardial infarction within 12 months before inclusion in the study. - New York Heart Association (NYHA) grade II or greater congestive heart failure. - Symptomatic arrhythmia or any arrhythmia requiring ongoing treatment. - Abnormal electrocardiogram (ECG), i.e., patients with the following are excluded: QT prolongation - QTc > 480 msec; signs of cardiac enlargement or hypertrophy; bundle branch block; partial blocks; signs of ischemia or necrosis, and Wolff Parkinson White patterns. - History or presence of valvular heart disease. - Uncontrolled arterial hypertension despite optimal medical therapy. - Previous mediastinal radiotherapy. - Previous treatment with doxorubicin at cumulative doses exceeding 400 mg/m2. B. History of significant neurological or psychiatric disorders. C. Active infection requiring systemic treatment. D. Significant non-neoplastic liver disease (e.g., cirrhosis). E. Known hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. F. Immunocompromised patients, including those known to be infected with the human immunodeficiency virus (HIV). G. Uncontrolled (i.e., requiring relevant changes in medication within the last month or hospital admission within the last three months) endocrine diseases (e.g., diabetes mellitus, hypo- or hyperthyroidism, adrenal disorder). Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the patient's participation in the study. The Investigator should feel free to consult the Study Coordinator or the Sponsor(s) in case of uncertainty in this regard. Limitation of the patient's ability to comply with the treatment or to follow-up at a participating center. Patients enrolled into this trial must be treated and followed at a participating center. Treatment with any investigational product within 30 days prior to inclusion in the study. Known hypersensitivity to any component of Zalypsis®. Other exclusion criteria may apply. 25aecec19d85d7a993d0a570275cfa7b 8607 Efficacy and Safety Study of CAL-101 in Patients With Indolent B-Cell Non-Hodgkin Lymphoma (DELTA) II Ajay Gopal, MD 20101820 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.8607.html http://www.clinicaltrials.gov/ct/search?term=NCT01282424 NCT01282424 Purpose The purpose of this study is to evaluate the efficacy and safety of CAL-101 in patients with previously treated indolent Non-Hodgkin Lymphoma (iNHL) that is refractory both to rituximab and to alkylating-agent-containing chemotherapy. The primary objective will be to assess the overall response rate. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Age =18 years. - Karnofsky performance score of =60 (Eastern Cooperative Oncology Group [ECOG] performance score of 0, 1, or 2). - Histologically confirmed diagnosis of B-cell iNHL, with histological subtype limited to the following: - Follicular lymphoma (FL) - Small lymphocytic lymphoma (SLL) with absolute lymphocyte count - Lymphoplasmacytoid lymphoma (LPL) - Marginal zone lymphoma (MZL) (splenic, nodal, or extranodal) - Prior treatment with =2 prior chemotherapy- or immunotherapy-based regimens for iNHL. - Prior treatment with rituximab and with an alkylating agent (eg, bendamustine, cyclophosphamide, ifosfamide, chlorambucil, melphalan, busulfan, nitrosoureas) for iNHL. - Lymphoma that is refractory to rituximab and to an alkylating agent. - For men and women of childbearing potential, willingness to abstain from sexual intercourse or employ an effective method of contraception during the study drug administration and follow-up periods. - Willingness and ability to provide written informed consent and to comply with the protocol requirements. Other eligibility criteria may apply. - Central nervous system or leptomeningeal lymphoma. - Known histological transformation from iNHL to diffuse large B-cell lymphoma. - History of a non-lymphoma malignancy except for the following: adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, localized prostate cancer, other adequately treated Stage 1 or 2 cancer currently in complete remission, or any other cancer that has been in complete remission for =5 years. - Evidence of ongoing systemic bacterial, fungal, or viral infection (excluding viral upper respiratory tract infections) at the time of initiation of study treatment. - Pregnancy or breastfeeding. - Ongoing alcohol or drug addiction. - Known history of drug-induced liver injury, chronic active HCV, chronic active HBV, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, ongoing extrahepatic obstruction caused by stones, cirrhosis of the liver or portal hypertension. - History of prior allogeneic bone marrow progenitor cell or solid organ transplantation. Ongoing immunosuppressive therapy, including systemic corticosteroids. Patients may be using topical or inhaled corticosteroids. - Prior therapy with CAL 101 - Exposure to another investigational drug within 3 weeks prior to start of study treatment. - Concurrent participation in another therapeutic treatment trial. - Prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, ECG finding, or laboratory abnormality that, in the investigator's opinion, could affect the safety of the patient; alter the absorption, distribution, metabolism or excretion of the study drug; or impair the assessment of study results. Other exclusion criteria may apply. ad1c44dc913af304ddbf5dae31f7d5b9 8610 Study of Erlotinib (Tarceva®) in Combination With OSI-906 in Patients With Advanced Non-small Cell Lung Carcinoma (NSCLC) With Activating Mutations of the Epidermal Growth Factor Receptor (EGFR) Gene II Keith Eaton, MD, PhD 20110053 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.8610.html http://www.clinicaltrials.gov/ct/search?term=NCT01221077 NCT01221077 A multicenter, randomized, double-blind, placebo-controlled, phase 2 study of Erlotinib (Tarceva®) in combination with OSI-906 in Patients with Advanced non-small cell lung carcinoma (NSCLC) with Activating Mutations of the Epidermal Growth Factor Receptor (EGFR) Gene who are Chemo naive. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Historically confirmed advanced NSCLC stages IIIB or IV; - Exon 19 deletion or exon 21 activating mutation in EGFR; - Formalin-fixed paraffin-embedded archival or fresh tissue sample representative of the tumor prior to randomization for EGFR mutation analysis to assess study eligibility must be provided unless EGFR mutation analysis is provided through a separate arrangement with OSI. Minimum tumor tissue requirement for patient eligibility is 66 microns in a form sufficient to generate five 10-micron thick tissue sections, and four 4-micron thick tissue sections with greater-than-or-equal-to 5 mm squared tumor area on each section; - Measurable disease according to RECIST (version 1.1); - ECOG performance status 0-1 (Appendix 13-2); - Must be able to take oral medication; - Fasting glucose <= 150 mg/dL (8.3 mmol/L). Concurrent use of non-insulinotropic anti hyperglycemic therapy is permitted if the dose has been stable for >= 4 weeks at the time of randomization; - Adequate hematopoietic, hepatic, and renal function as follows: Neutrophil count >= 1500/uL; Platelet count >= 100,000/uL; Serum creatinine <= 1.5 x ULN; Potassium, magnesium, and calcium within normal limits (supplementation is permitted); Total bilirubin <= 1.5 x ULN; and AST and ALT <= 2.5 x ULN, or <= 5 x ULN if patient has documented liver metastases; - Patients - both male and female - with reproductive potential (ie, menopausal for less than 1 year and not surgically sterilized) must agree to practice effective contraceptive measure throughout the study. Women of childbearing potential must provide a negative pregnancy test (serum or urine) within 14 days prior to randomization. Men must agree not to donate sperm while on study drug and up to 90 days following the last dose of study drug; - Patients must provide written informed consent to participate in the study; - Patients may not have received chemotherapy for advanced NSCLC. Previous adjuvant and/or neo-adjuvant treatment for NSCLC is permitted; - Prior radiation therapy is permitted provided patients have recovered from the acute, toxic effects of radiotherapy prior to randomization. A minimum of 21 days must have elapsed between the end of radiotherapy and randomization; and - Prior surgery is permitted provided that the surgery was done >= 28 days prior to randomization and adequate wound healing has occurred prior to randomization. Other eligibility criteria may apply. - Prior exposure to agents directed at the HER axis (eg, erlotinib, gefitinib, and cetuximab); or - Prior IGF-1R inhibitor therapy; or - Malignancies other than NSCLC within the past 3 years (exceptions if curatively treated; basal or squamous cell carcinoma of skin; locally advanced prostate cancer; ductal carcinoma in situ of breast; in situ cervical carcinoma; and superficial bladder cancer); - Diabetes mellitus currently requiring insulinotropic or insulin therapy (Appendix 13-7); - Use of proton pump inhibitors such as omeprazole within 14 days prior to randomization (see Section 6.6.1.3). H2-receptor antagonists such as ranitidine are not excluded (see Section 6.6.2.7); - Symptomatic brain metastases that are not stable, require steroids, or that have required radiation within 21 days prior to randomization; - Prior investigational agent within 21 days prior to randomization; - History of poorly controlled gastrointestinal disorders that could affect the absorption of study drug (eg, Crohn's disease or ulcerative colitis); - History (within last 6 months) of significant cardiovascular disease unless the disease is well-controlled. Significant cardiac disease includes second/third degree heart block; clinically significant ischemic heart disease; superior vena cava (SVC) syndrome; poorly controlled hypertension; congestive heart failure of New York Heart Association (NYHA) Class II or worse (slight limitation of physical activity; comfortable at rest, but no ordinary physical activity results in fatigue, palpitation, or dyspnea); - History of arrhythmia (multifocal premature ventricular contractions [PVCs], bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) that is symptomatic or requires treatment (>= grade 3), left bundle branch block (LBBB), or asymptomatic sustained ventricular tachycardia are not allowed. Patients with atrial fibrillation controlled by medication are not excluded; - Mean QTcF interval >= 450 msec at screening; - Use of drugs that have a known risk of causing Torsades de Pointes (TdP) ('Torsades List' on www.azcert.org/medical-pros/drug-lists/bycategory.cfm) are prohibited within 14 days prior to randomization (see Appendix 13-3); - Use of strong/moderate CYP1A2 inhibitors such as ciprofloxacin and fluvoxamine. Other less potent CYP1A2 inhibitors/inducers are not excluded (see Appendix 13-5); - Use of strong/moderate CYP3A4 inhibitors and inducers (see Appendix 13-5); - History of cerebrovascular accident (CVA) within 6 months prior to randomization or that resulted in ongoing neurologic instability; - History of any psychiatric or neurologic condition that might impair the patient's ability to understand or to comply with the requirements of the study or to provide informed consent; - Pregnant or breast-feeding females; - History of allergic reactions attributed to compounds of similar chemical or biologic composition to the study drug; and/or - Active infection, serious underlying medical condition (including any type of active seizure disorder within 12 months prior to randomization), symptomatic brain metastases, or serious chronic illness that would impair the ability of the patient to receive study drug. Other exclusion criteria may apply. 2297374375b30c64e1729b608c6c5bb2 8761 A Safety and Efficacy Study of Patients With Metastatic or Locally Advanced (Unresectable) Chondrosarcoma II Robin Jones 20110074 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.8761.html http://www.clinicaltrials.gov/ct/search?term=NCT01310816 NCT01310816 Purpose IPI-926 is an inhibitor of the hedgehog pathway. IPI-926 may improve therapeutic outcomes in patients with Chondrosarcoma. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - At least 18 years of age at the time of signing informed consent. - Pathologically diagnosed conventional chondrosarcoma. Patients must have tumor sample(s) available or provide tumor samples from a new biopsy - Metastasis to at least 1 location or locally advanced disease that is deemed unresectable by a surgeon - At least 1 radiologically measurable target lesion per RECIST 1.1. - Patients must have documented radiographic progression of disease within the 6-month period prior to screening. (MRI or CT Scan) - Eastern Cooperative Oncology Group (ECOG) performance status: 0 or 1. - Life expectancy of at least 3 months - All women of child-bearing potential (WCBP), all sexually active male patients, and all partners of patients must agree to use adequate methods of birth control throughout the study and for 30 days after the last dose of study drug. - Ability to adhere to the study visit schedule and all protocol requirements. - Voluntarily signed an informed consent form. Other eligibility criteria may apply. - Other invasive malignancies diagnosed within the last 5 years, except non-melanoma skin cancer and localized cured prostate and cervical cancer. - Systemic anti-cancer therapy within 21 days prior to the first dose of study drug, or radiotherapy within 14 days prior to the first dose of study drug. - Prior treatment with a Hedgehog pathway inhibitor - Medically significant surgical procedures or significant traumatic injury within 28 days before Day 1. - Inadequate hematologic function defined by: - Absolute neutrophil count (ANC) <1,000 cells/mm3 (1.0 x 109/L). - Hemoglobin <8.0 g/dL (80 g/L) (may be increased to this level with transfusion as long as there is no evidence of active bleeding). - Inadequate hepatic function defined by: - Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >2.5 x upper limit of normal (ULN). - Total bilirubin >1.5 x ULN (with the exception of patients with Gilbert's disease). - Cirrhotic liver disease, ongoing alcohol abuse, or known chronic active or acute hepatitis. - Inadequate renal function defined by serum creatinine >1.5 x ULN - Patients with a history of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months. - Presence of active infection or systemic use of antibiotics within 72 hours of treatment. - Significant co-morbid condition or disease, which in the judgment of the Investigator, would place the patient at undue risk or interfere with the study. Examples include, but are not limited to sepsis and recent significant traumatic injury. - Known human immunodeficiency virus (HIV) positivity. - Known hypersensitivity to IPI-926, or any of the excipients in IPI-926 or placebo capsules. - Pregnant or lactating women. Other exclusion criteria may apply. 1f534e5ac87b1a7dd50430019355529f 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 8601 A Study of MEDI-575 in Subjects With Recurrent Glioblastoma Multiforme II Marc Chamberlain, MD 20110231 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.8601.html http://www.clinicaltrials.gov/ct/search?term=NCT01268566 NCT01268566 Purpose The primary objective of this Phase II study is to evaluate the progression-free survival at 6 months in adult subjects with a first recurrence of Glioblastoma Multiforme who are treated with MEDI-575. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Written informed consent and HIPAA authorization (applies to covered entities in the USA only) obtained from the subject/legal representative prior to performing any protocol-related procedures, including screening evaluations - Age =18 years old at the time of screening - Histologically confirmed diagnosis of World Health Organization Grade IV malignant glioma (glioblastoma or gliosarcoma) - Previous first line treatment with radiotherapy and temozolomide (treatment prior to radiation and temozolomide permitted, [ie, Gliadel]) - Documented first recurrence of GBM by diagnostic biopsy or by contrast-enhanced magnetic resonance imaging (MRI) as per Updated Response Assessment Criteria of High Grade Gliomas- Neuro-Oncology Working Group (Wen et al, 2010) - Life expectancy = 12 weeks - Adequate hematologic and organ function - Negative serum pregnancy test (women only) - Two methods of birth control for female participants of child-bearing potential or male participants with their female partners of child-bearing potential Other eligibility criteria may apply. - Treatment with any chemotherapy, radiotherapy, immunotherapy, biologic, hormonal therapy or investigational agent 30 days prior to study entry - Concurrent enrollment in another clinical study involving an investigational agent - Employees of the clinical study site or any other individuals involved with the conduct of the study, or immediate family members of such individuals - Previous mAb treatment specifically directed against PDGF or PDGF receptors - Previous bevacizumab or other VEGF and anti-angiogenic treatment - More than 1 recurrence of GBM - Any surgery (not including minor diagnostic procedures) within 2 weeks prior to baseline disease assessments; or not fully recovered from any side effects of previous procedures - History of serious allergy or reaction to any component of the MEDI-575 formulation - New York Heart Association = Grade 2 congestive heart failure within 6 months prior to study entry - Uncontrolled or significant cardiovascular disease - History of other invasive malignancy within 5 years prior to study entry except for cervical carcinoma in situ (CIS), non-melanomatous carcinoma of the skin or ductal carcinoma in situ (DCIS) of the breast that have been surgically cured - History of active human immunodeficiency virus or active hepatitis B or C viral infection will be excluded to eliminate the risk of increased AEs due to immune compromise. - Systemic immunosuppressive therapy. - Subjects taking corticosteroids must be on a stable dose for 7 days prior to initiation of treatment with MEDI-575 16) Presence of extracranial metastatic or leptomeningeal disease Other exclusion criteria may apply. 1c96a0f397802dee2670745092e680e7 8719 Open Label Regorafenib Study to Evaluate Cardiovascular Safety Parameters, Tolerability, and Anti-tumor Activity I Robin Jones 20110500 83 Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8719.html http://www.clinicaltrials.gov/ct/search?term=NCT01339104 NCT01339104 Open label Phase I study of Regorafenib to evaluate cardiovascular safety, tolerability and anti-tumor activity in patients with advanced solid tumors Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1 Adequate bone marrow, liver, and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to dosing: - Hemoglobin (Hb) >/= 9.0 g/dL, Absolute neutrophil count (ANC) >/= 1500/mm³, Platelet >/= 100,000/mm³, Total bilirubin </= 1.5 times upper limit of normal (ULN), Alkaline phosphatase </= 4 x ULN - Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) </= 2.5 times ULN (</= 5.0 x ULN for subjects with liver involvement of their cancer), International Normalized Ratio (INR) or Partial Thromboplastin Time (PTT) < 1.5 x ULN, Serum creatinine </= 1.5 times ULN and glomerular filtration rate (GFR) >/= 30 ml/min/1.73 m² according to the MDRD (Modified Diet in Renal Disease) abbreviated formula, Lipase </= 1.5 x ULN - Left Ventricular Ejection Fraction (LVEF) >/= 50 % as assessed at the Baseline Multigated Acquisition (MUGA) scan - QTc (Q-T corrected) </= 470 msec at Screening Having advanced, refractory disease Life expectancy of at least 3 months Recovery from any previous drug/procedure-related toxicity to Common Toxicological Criteria (CTC) Grade 0 or 1 levels (except alopecia), or to baseline preceding the prior treatment. Other eligibility criteria may apply. History of cardiac disease: congestive heart failure > New York Heart Association (NYHA) Class II; active coronary artery disease (unstable angina [anginal symptoms at rest] or new-onset angina [began within the last 3 months] or myocardial infarction within the past 6 months). Uncontrolled hypertension (failure of diastolic blood pressure to fall below 90 mmHg, despite the use of >/= 3 antihypertensive drugs or systolic blood pressure greater than 150 mmHg) History of or known human immunodeficiency virus (HIV) infection or active hepatitis B or C. Subjects with serious non-healing wound, ulcer, or bone fracture Subjects with arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism within the 6 months before start of study medication Persistent proteinuria of CTC Grade 3 or higher (> 3.5 g/24 hours, measured by urine protein/creatinine ratio on a random urine sample) Symptomatic metastatic brain or meningeal tumors unless the subject is > 6 months from definitive therapy, has no evidence of tumor growth on an imaging study within 2 weeks prior to study entry, and is clinically stable with respect to the tumor at the time of study entry Clinically significant bleeding (CTC AE Grade 3 or higher) within 30 days before start of study medication. Subjects with seizure disorder requiring anticonvulsant medication History of organ allograft Other exclusion criteria may apply. 1f1098a803147d91f744545ed355d5e2 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 8679 ARCHER 1009 : A Phase 3 Study Of PF-00299804, A Pan-HER Inhibitor, Vs. Erlotinib In The Treatment Of Advanced Non-Small Cell Lung Cancer III Renato Martins, MD, MPH 20110772 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.8679.html http://www.clinicaltrials.gov/ct/search?term=NCT01360554 NCT01360554 This is a multinational, multicenter, randomized,double-blinded, Phase 3 study comparing the efficacy and safety of treatment with PF-00299804 to treatment with erlotinib in patients with advanced non-small cell lung cancer, previously treated with at least one prior regimen. Analyses of primary objective (Progression Free Survival) will be done in two co-primary populations as defined in the protocol. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Evidence of pathologically confirmed, advanced NSCLC (with known histology). - Prior treatment with at least one and no more than two systemic therapy regimens (at least one must be standard chemotherapy for advanced NSCLC). - Adequate tissue sample must be submitted prior to randomization for tumor biomarker analyses. - Adequate renal, hematologic, liver function. - ECOG PS of 0-2. - Radiologically measurable disease. Other eligibility criteria may apply. - Small cell histology. - Symptomatic brain mets or known leptomeningeal mets. - Prior therapy with agent known or proposed to be active by action on EGFR tyrosine kinase or other HER family proteins. - Uncontrolled medical disorders. Other exclusion criteria may apply. 83907d019f87933a54b2c821b9d845ed 8578 Study of Cabozantinib (XL184) in Adults With Advanced Malignancies II Tia Higano, MD 20110790 13; 45; 46; 52; 65; 66; 71; 83; 84 Breast Cancer; Liver Cancer; Lung Cancer; Melanoma; Ovarian Cancer; Pancreatic Cancer; Prostate Cancer; Solid Tumors; Stomach Cancer Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8578.html http://www.clinicaltrials.gov/ct/search?term=NCT00940225 NCT00940225 The purpose of this study is to determine whether or not XL184 demonstrates anti-tumor activity in selected tumor types under a randomized discontinuation trial (RDT) design. Subjects who have responded to study drug after 12 weeks of open-label XL184 administration will continue to take XL184. Subjects who are clearly progressing will discontinue study treatment and subjects who demonstrate stable disease will be randomized to either XL184 or placebo. For individual patients, once disease progression is observed, the blind will be broken and subjects who were randomized to placebo will be offered the option to receive open-label XL184. Subjects who progressed while taking XL184 will discontinue study treatment. Emerging data may support enrollment in an open-label, non-randomized expansion cohort (NRE). Subjects with prostate and ovarian cancers will enroll in these expansion cohorts. Other tumor types may similarly be expanded, as supporting data emerges. Not all clinical sites will be participating in the expansion cohorts; some sites may not enroll subjects with prostate or ovarian cancer. Due to the nature of the study design, enrollment to certain tumor type cohorts may open and close. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both The subject has a cytologically or histologically and radiologically confirmed, advanced, recurrent, or metastatic solid tumor of the nine types listed below: - Pancreatic Cancer - Castration-Resistant Prostate Cancer (CRPC) - Hepatocellular Carcinoma (HCC) - Gastric or Gastroesophageal Junction Cancer - Melanoma - Small Cell Lung Cancer (SCLC) - Ovarian cancer, primary peritoneal or fallopian tube carcinoma - Breast cancer that is one of the following subtypes: estrogen receptor positive breast cancer, estrogen receptor/progesterone receptor/HER2-negative (triple-negative), or inflammatory (regardless of receptor status) disease histology - Non-Small Cell Lung Cancer (NSCLC) Certain requirements for prior therapies may apply The subject has documented progressive disease at screening Subjects having any tumor type of other than CRPC must have at least one lesion that is not within a previously irradiated field and is measurable on CT or MRI scan The subject has recovered to baseline or CTCAE = Grade 1 from toxicities related to prior treatment (some exceptions apply) The subject is = 18 years old on the day of consent Tissue samples from archival or fresh tissue, or a tissue block of the subject's tumor The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 The subject has adequate organ function The subject is capable of understanding and complying with the protocol requirements and has signed the informed consent document Sexually active fertile subjects (male and female), and their partners, must agree to use medically accepted methods of contraception during the course of the study and for 3 months after the last dose of the study drug(s) Female subjects of childbearing potential must have a negative pregnancy test at screening Other eligibility criteria may apply. The subject has experienced clinically-significant hematemesis or hemoptysis of >0.5 teaspoon of red blood, or other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment The subject has a cavitating pulmonary lesion(s) or a pulmonary lesion abutting or encasing a major blood vessel Certain restrictions on prior treatments apply The subject has received drugs used to control loss of bone mass within 4 weeks prior to the first dose of study treatment The subject has known symptomatic or uncontrolled brain metastases or epidural disease The subject has prothrombin time/International Normalized Ratio (PT/INR) or partial thromboplastin time (PTT) test results that are above (1.3x)the laboratory upper limit of normal The subject has a corrected QT interval(QTcF)>500 ms at screening The subject requires concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or Coumadin-related agents, heparin, thrombin or FXa inhibitors, and antiplatelet agents (low-dose aspirin (=81 mg/day), low-dose warfarin (=1mg/day, and prophylactic low molecular weight heparin (LMWH) are permitted) The subject has uncontrolled, significant intercurrent illness The subject is unable to swallow capsules The subject is pregnant or breastfeeding The subject has a previously-identified allergy or hypersensitivity to components of the study treatment formulation The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee The subject has had another diagnosis of malignancy requiring systemic treatment within the last two years, unless non-melanoma skin cancer, in-situ carcinoma of the cervix, or superficial bladder cancer Other exclusion criteria may apply. 94b9bcbee9fa73e66f031c6a92128c3b 8725 Study of BMN 673, a PARP Inhibitor, in Patients With Advanced Hematological I Ajay Gopal, MD 20110958 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.8725.html http://www.clinicaltrials.gov/ct/search?term=NCT01399840 NCT01399840 This is a two-arm, open-label study to determine the maximum tolerated dose (MTD) and assess the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of BMN 673 in patients with Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS), Chronic Lymphocytic Leukemia (CLL) and Mantle Cell Lymphoma (MCL). Arm 1 will enroll patients with either AML or MDS; Arm 2 will enroll patients with either CLL or MCL. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both Eastern Cooperative Oncology Group (ECOG) performance status = 1 Arm 1 AML/MDS: Must have available tissue Arm 2 CLL/MCL: Must have available tissue Have adequate organ function as defined below: - Serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) </= 2.5 X upper limit of normal (ULN); - Total serum bilirubin </= 1.5 X ULN; Able to take oral medications Recovered from acute toxicity of prior treatment Willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any research-related procedures. If sexually active, must be willing to use an acceptable method of contraception during therapy and for 30 days after the last dose of BMN 673. If female of childbearing potential, must have a negative serum pregnancy test at screening and be willing to have additional pregnancy tests during the study. Willing and able to comply with all study procedures. Other eligibility criteria may apply. Acute promyelocytic leukemia, APL [AML with t(15;17)(q22;q12), PML-RARA and variants]. Disease-specific exclusion criteria: - AML: i. Marrow cellularity < 25% ii. Circulating blasts > 50,000/mm3 b. MCL and CLL: i. Platelet count < 50,000/mm3 ii. Neutrophil count < 1000/mm3 Autologous bone marrow transplant < 6 months before Cycle 1 Day 1 Prior allogeneic bone marrow transplant < 6 months before Cycle 1 Day 1 and/or with the presence of graft versus host disease (GVHD) Prior treatment: - AML: anti-leukemia treatment within 14 days before Cycle 1 Day 1; hydroxyurea treatment within 7 days before Cycle 1 Day 1. - CLL, MCL or MDS: anti-lymphoma/leukemia treatment within 28 days before Cycle 1 Day 1; CLL/MCL patients who have received transfusion, hematopoietic growth factors within 7 days before Cycle 1 Day 1. Symptomatic central nervous system (CNS) involvement. Known to have human immunodeficiency virus (HIV) or active hepatitis C virus (HCV) or hepatitis B virus (HBV). Major surgery within 28 days before Cycle 1, Day 1. Active peptic ulcer disease. Active gastrointestinal tract disease with malabsorption syndrome. Requirement for IV alimentation. Prior surgical procedures affecting absorption. Uncontrolled inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis). Myocardial infarction within 6 months before Cycle 1 Day 1, symptomatic congestive heart failure (New York Heart Association > class II), unstable angina, or unstable cardiac arrhythmia requiring medication. Breastfeeding at screening or planning to become pregnant (self or partner) at any time during study participation. Use of any investigational product or investigational medical device within 28 days before Cycle 1, Day 1. Concurrent disease or condition that would interfere with study participation or safety, such as: - CLL/MCL patients with active, clinically significant infection requiring the use of parenteral anti-microbial agents, or grade > 2 infection by NCI CTCAE (v4.03) within 14 days before Cycle 1, Day 1(AML/MDS patients with controlled infection are eligible for the study with no specific time requirement prior to Cycle 1, Day 1); - Clinically significant bleeding diathesis or coagulopathy, including known platelet function disorders; - Non-healing wound, ulcer, or bone fracture. Patients who have received prior treatment with a PARP inhibitor are not eligible for Part 2 of the study (expansion), but are eligible for Part 1 (dose escalation) of the study. Other exclusion criteria may apply. 9e140cc964c632e2c08fee3121c3303a 8690 A Study in Metastatic Cancer and Advanced or Metastatic Unresectable Pancreatic Cancer I/II Samuel Whiting, MD, PhD 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. a66175b42ea98ee328319fa6c715d37b 7870 Open-label Study to Evaluate the Safety, PK, and PD of MEK Inhibitor GSK1120212 in Subjects With Relapsed or Refractory Leukemias I/II Roland Walter, MD 2344.00 1; 2; 18; 19; 36; 43; 61 Acute Lymphoid Leukemia (ALL); Acute Myeloid Leukemia (AML); Chronic Lymphoid Leukemia (CLL); Chronic Myeloid Leukemia (CML); 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.7870.html http://www.clinicaltrials.gov/ct/search?term=NCT00920140 NCT00920140 Purpose: MEK111759 is a dose-escalation, Phase I/II, open-label study to determine the recommended dose and regimen for the orally administered MEK inhibitor GSK1120212 in subjects with relapsed or refractory leukemias. The recommended dose and regimen will be selected based on the safety, pharmacokinetic, and pharmacodynamic profiles. This study will identify the maximum tolerated and recommended Phase II doses using a dose-escalation procedure. Dose escalations will continue based on predefined parameters until a maximum tolerated dose is established. In Phase II, the clinical efficacy of GSK1120212 in subjects with relapsed or refractory acute myeloid leukaemia will be determined. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both Phase I - Subjects must have relapsed/refractory leukemias for which no standard therapies are anticipated to result in a durable remission. Subjects with poor-risk myelodysplasia (MDS) and chronic melomonocytic leukemia (CMML) are also eligible. Relapsed/refractory leukemias include acute non-lymphocytic leukemia (AML), acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), or chronic myelogenous leukemia (CML) in blast crisis. Subjects with agnogenic myeloid metaplasia (AMM) are also eligible. Subjects with a haematological malignancy associated with human immunodeficiency virus (HIV) infection or solid organ transplant are NOT eligible. - Subjects who have previously received an autologous stem cell transplant are allowed if a minimum of three months has elapsed from the time of transplant (T0) and the subject has recovered from transplant-associated toxicities prior to the first dose of GSK1120212. - Subjects with a history of allogeneic stem cell transplant are eligible for study participation provided the following eligibility criteria are met: transplant was greater than 100 days prior to study enrolment, subject has not taken immunosuppressive medications (per protocol) for at least 1 month, no signs or symptoms of graft versus host disease other than Grade 1 skin involvement, no active infection, subject meets the remainder of the eligibility criteria outlined in this protocol. - Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 2. - Life expectancy of at least four weeks. - Able to swallow and retain oral medication. - Male subjects must agree to use one of the contraception methods listed in the protocol. - Female subjects must be of non-childbearing potential as listed in the protocol or using a contraception method listed in the protocol. - Calcium Phosphate Product less than or equal to 4.0 mmol (squared)/L (squared) or 50mg (squared)/dL (squared). - Subjects must have adequate organ function as specified in the protocol. Phase II - Confirmed diagnosis of one of the following: Relapsed or refractory acute myeloid leukemia (AML), Secondary AML including AML arising from antecedent hematologic diseases (e.g., myelodysplastic syndrome, myeloproliferative disorders, or therapyrelated AML), Elderly subjects older than 60 years of age with AML, previously untreated and who are not candidates for or have refused standard chemotherapy Other eligibility criteria may apply. Phase I - Currently receiving cancer therapy as specified in the protocol. - Received corticosteroids or imatinib within 24h of GSK1120212 administration. - Received gemtuzumab ozogamicin (myelotarg) within two weeks of GSK1120212 adminstration. - Received an investigational anti-cancer drug within four weeks or five half-lives, whichever is shorter of GSK1120212 administration, as specified in the protocol. - Received major surgery, radiotherapy, or immunotherapy within four weeks of GSK1120212 administration. - Received chemotherapy regimens with delayed toxicity within the last four weeks (six weeks for prior nitrosourea or mitomycin C). Received chemotherapy regimens given continuously or on a weekly basis with limited potential for delayed toxicity within the last two weeks. - Received a MEK inhibitor. - Current use of a prohibited medication per protocol. - Current use of warfarin. Low molecular weight heparin and prophylactic low-dose warfarin are permitted per protocol. - Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of drugs. - History of RVO. - Visible retinal pathology as assessed by ophthalmologic exam that is considered a risk factor for retinal vein thrombosis. - Intraocular pressure greater than 21mm Hg as measured by tonography. - Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol. - Condition that in the investigator's opinion would jeopardize compliance with the protocol. - Symptomatic or untreated central nervous system involvement by the hematologic malignancy, including primary CNS lymphoma. Subjects who were previously treated for CNS involvement, and are asymptomatic without anti-epileptic medications for at least two months are eligible. - Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory, hepatic, renal, or cardiac disease). - Unresolved toxicity greater than Grade 1 from previous anti-cancer therapy except alopecia (if applicable) unless agreed to by a GSK Medical Monitor and the investigator. - QTc interval greater than 480 msecs. - History of acute coronary syndromes (including unstable angina), coronary angioplasty or stenting within the past 24 weeks. - Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system. - Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drug, dimethyl sulfoxide (DMSO), or excipients . (To date there are no known FDA approved drugs chemically related to GSK1120212). - Pregnant or lactating female. - Unwillingness or inability to follow the procedures outlined in the protocol. Other exclusion criteria may apply. 492649c5f0c2d4bd0f4e9e18c9b0ce27 7894 Study Evaluating the Safety and Tolerability of Weekly Dosing of Oral MLN9708 in Adult Patients With Relapsed and Refractory Multiple Myeloma I Bill Bensinger, MD 2360.00 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.7894.html http://www.clinicaltrials.gov/ct/search?term=NCT00963820 NCT00963820 Purpose This study will determine the safety profile, tolerability, and maximum tolerated dose (MTD) and disease response of the weekly dosing MLN9708 administered orally in patients with relapsed and refractory multiple myeloma. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both Each patient must meet all of the following eligibility criteria to be enrolled in the study: - Adult patients with multiple myeloma who have relapsed following at least 2 lines of therapy. - Patients must have measurable disease. - Appropriate functional status, including the recovery from the effects of prior antineoplastic therapy, and acceptable organ function as described in the protocol. - Female patients who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or abstain from heterosexual intercourse. - Male patients who agree to practice effective barrier contraception or agree to abstain from heterosexual intercourse. - Willing and able to give written informed consent. - Suitable venous access for study-required blood sampling. Other eligibility criteria may apply. - Peripheral neuropathy that is greater or equal to Grade 2. - Major surgery or, serious infections, or infections that required systematic antibiotic therapy within 14 days before the first dose of study drug. - Life-threatening illness unrelated to cancer. - Diarrhea that is greater than Grade 1 as outlined in the protocol - Systemic antineoplastic or radiation therapy within 14 days or cytotoxic agents, or treatment with any investigational products within 21 days before the first dose of study treatment. - Treatment with any investigational proteasome inhibitor. - Systemic treatment with prohibited medications that are outlined in the protocol within 14 days of study treatment. - Ongoing therapy with corticosteroids greater than 10mg of prednisone or its equivalent per day. - Central nervous system involvement. - Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure, angina, or myocardial infarction within the past 6 months. - Known human immunodeficiency virus (HIV) positive, hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection. - Serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to the protocol. - Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption of tolerance of MLN9708 including difficulty swallowing. Other exclusion criteria may apply. 34bed3e7653f87636c2ab5bef53c10b4 8002 A Study of the Safety and Efficacy of CNTO 328 in Combination With Best Supportive Care Compared to Best Supportive Care in Patients With Multicentric Castleman's Disease II Corey Casper 2366.00 49 Lymphoproliferative Disease Judy Schramm 206/667-2884 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8002.html http://www.clinicaltrials.gov/ct/search?term=NCT01024036 NCT01024036 The study is being conducted to demonstrate that CNTO 328 in combination with best supportive care is superior to best supportive care in terms of durable tumor and symptomatic response (reduction in tumor size and the symptoms for at least 18 weeks) and has an acceptable benefit risk profile in among patients with multicentric Castleman's disease. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Measureable and symptomatic Multicentric Castleman's Disease - Adequate organ function as assessed by Laboratory values evaluated by the investigator to determine eligibility prior to treatment - ECOG Performance Status of 0, 1, or 2 - Corticosteroids dose that does not exceed 1 mg/kg/day of prednisone, and has remained stable or decreased over the 4 weeks before treatment Other eligibility criteria may apply. - HIV or HHV-8 positive - Skin lesions as sole measurable manifestation of MCD - Prior exposure to IL-6 or IL-6 receptor targeted therapies - Previous lymphoma - Certain Malignancies, from which the patient has been disease-free for = 3 years - Concurrent medical condition or disease that may interfere with study participation Other exclusion criteria may apply. c5adfa7ab617d3fa4e4cbb06b26822a4 8159 A Phase 3 Study of Brentuximab Vedotin (SGN-35) in Patients at High Risk of Residual Hodgkin Lymphoma Following Stem Cell Transplant (The AETHERA Trial) III Leona Holmberg, MD, PhD 2374.00 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.8159.html http://www.clinicaltrials.gov/ct/search?term=NCT01100502 NCT01100502 Purpose: This is a randomized, double-blind, placebo-controlled, multicenter phase 3 trial to evaluate the efficacy and safety of brentuximab vedotin (SGN-35) and best supportive care (BSC) compared to placebo and BSC in treatment of residual Hodgkin lymphoma (HL) following autologous stem cell transplant (ASCT). Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Patients with HL who have received ASCT in the previous 30-45 days - Patients at high risk of residual HL post ASCT - Histologically-confirmed HL - ECOG of 0 or 1 - Adequate organ function Other eligibility criteria may apply. - Previous treatment with brentuximab vedotin - Previously received an allogeneic transplant - Patients who were determined to have a best clinical response of progressive disease with salvage treatment immediately prior to ASCT - History of another primary malignancy that has not been in remission for at least 3 years - Post ASCT or current therapy with other systemic anti-neoplastic or investigational agents Other exclusion criteria may apply. b26566420321be22563d4b87572ed7b7 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 8368 Safety and Efficacy Study of TRU-016 Plus Bendamustine Versus Bendamustine Alone in Relapsed Chronic Lymphocytic Leukemia I/II John Pagel, MD, PhD 2441.00 36; 43 Hematologic Malignancies; Leukemia Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8368.html http://www.clinicaltrials.gov/ct/search?term=NCT01188681 NCT01188681 The objective of the first part of the study is to determine a safe dose of TRU-016 that can be used in combination with bendamustine in patients with relapsed CLL. The objectives of the second part of the study are to compare the safety and efficacy of TRU-016 in combination with bendamustine to bendamustine alone in patients with relapsed CLL Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Diagnosis of relapsed CLL with 1 to 3 prior treatments - Demonstrated active disease requiring treatment - No prior bendamustine treatment - Not refractory to fludarabine or other purines, either as a single agent or in combination - Age >/=18 years; male or female - ECOG performance status of </= 2 - Creatinine clearance > 40 mL/min - ANC >/= 1,200/mm3 - Platelets >/= 75,000/mm3 - Lymphocytes >/= 5,000/mm3 in Phase 1b Other eligibility criteria may apply. - Treatment with rituximab or other B-cell depleting agent within 30 days or alemtuzumab within 12 weeks - Previous anticancer therapy within 30 days - Refractory to prior fludarabine or other purine analog therapy either as a single agent or in combination - Receipt of prior bendamustine or TRU-016 - Receipt of an investigational therapy or major surgery within 30 days - Previous or concurrent additional malignancy (some exceptions apply) - Any significant concurrent medical diseases or conditions - Positive serology for HIV or hepatitis C, hepatitis B surface antigen positive or hepatitis B core antibody positive. - Pregnant or breast feeding - Drug or alcohol abuse - Allergic to mannitol Other exclusion criteria may apply. c96d6bc640dc7de212b3fe53f2f689dc 8462 Study of Pomalidomide in Persons With Myeloproliferative-Neoplasm-Associated Myelofibrosis and RBC-Transfusion-Dependence (RESUME) III Joachim Deeg, MD 2465.00 36; 61 Hematologic Malignancies; 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.8462.html http://www.clinicaltrials.gov/ct/search?term=NCT01178281 NCT01178281 Purpose: The objective of this study is to determine whether pomalidomide is safe and effective in reversing RBC-transfusion-dependence in persons with myeloproliferative neoplasm (MPN)-associated myelofibrosis. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Age =18 years - Myeloproliferative-neoplasm (MPN)-associated myelofibrosis - RBC-transfusion-dependence - Bone marrow biopsy within 6 months - Inappropriate to receive blood cell or bone marrow allotransplant, erythropoietin and androgenic steroids - ECOG performance score =2. - Agree to follow pregnancy precautions as required by the protocol. - Agree to receive counseling related to teratogenic and other risks of pomalidomide - Agree not to donate blood or semen Other eligibility criteria may apply. - Prior blood cell or bone marrow allotransplant. - Use of drugs to treat MPN-associated myelofibrosis =30 - 42 days before starting study drug. - Treatment with erythropoietin or androgenic steroids =84 days before starting study drug. - Anemia due to reasons other than MPN-associated myelofibrosis. - Pregnant or lactating females. - More than 10% blasts during the 8 weeks before starting study drug. - Prior history of cancer, other than due to MPN-associated myelofibrosis unless the subject has been cancer-free =5 years. Basal cell carcinoma of the skin, squamous cell carcinoma of the skin prostate cancer stage-1 are allowed at any time. - HIV-infection, active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection. - Prior treatment with pomalidomide. - Allergic reaction or rash after treatment with thalidomide or lenalidomide - Any of the following laboratory abnormalities: - Neutrophils <0.5x10e9 /L - Platelets <25 x 10e9 /L - Estimated glomerular filtration rate (kidney function) <30 mL/min - AST and ALT >3.0 x upper limit of normal - Direct bilirubin =3 x ULN; - Un-controlled hyperthyroidism or hypothyroidism. - Deep venous thrombosis (DVT) or pulmonary embolus (PE) <6 months before starting study drug - Clinically-important heart disease within the past 6 months Other exclusion criteria may apply. 6e665ee61bd95163c4f2ca46d5168974 8552 A Study to Evaluate the Safety and Efficacy of Inactivated Varicella-zoster Vaccine (VZV) as a Preventative Treatment for Herpes Zoster (HZ) and HZ-related Complications in Participants Undergoing Hematopoietic Cell Transplants (HCTs) (Study No. V212-001 AM3) III Steven Pergam, MD 2472.00 36 Hematologic Malignancies Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8552.html http://www.clinicaltrials.gov/ct/search?term=NCT01229267 NCT01229267 Purpose This is a study to determine whether investigational V212 reduces the incidence of herpes zoster (HZ) compared to placebo when administered to recipients of autologous hematopoietic cell transplants (HCT). Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Men and women at least 18 years of age - Has prior history of varicella, antibodies to VZV (documented prior to receipt of blood products), or residence in a country with endemic VZV infection for =30 years or if participant is <30 years old, attended primary or secondary school in a country with endemic VZV infection. - Scheduled to undergo an autologous hematopoietic cell transplant within 60 days of enrollment - Is highly unlikely to conceive during the time period starting 2 weeks prior to enrollment through 6 months from last vaccination dose - Female participants of childbearing potential must have a negative serum or urine pregnancy test. Other eligibility criteria may apply. - History of hypersensitivity reaction to any vaccine component - Prior history of herpes zoster within 1 year of enrollment - Prior receipt of any varicella or zoster vaccine - More than 2 relapses of the underlying cancer (participants with Hodgkin's lymphoma may have had more than 2 relapses) - Expectation of tandem transplant procedure - Is expected to receive >6 months (>180 days) of prophylactic antiviral therapy post-HCT. - Is pregnant or breastfeeding or expecting to conceive within the period of 2 weeks prior to enrollment through 6 months from last vaccination dose. - Has received a live virus vaccine or is scheduled to receive a live virus vaccine in the period from 4 weeks prior to Dose 1 through 28 days Postdose 4. - Has received an inactivated vaccine or is scheduled to receive an inactivated vaccine in the period between 7 days prior to and 28 days following Doses 1 through 4. Other exclusion criteria may apply. f52841b1e7e5ccc196f01263643c6224 8559 Safety, Pharmacokinetics, and Pharmacodynamics of Oral Azacitidine in Subjects With Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia and Acute Myelogenous Leukemia I Bart Scott, MD 2474.00 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.8559.html http://www.clinicaltrials.gov/ct/search?term=NCT00528983 NCT00528983 The purpose of this study is to determine whether a tablet form of azacitidine that taken by mouth is safe. This Phase I study will also look at different doses and different treatment schedules in order to better understand the effects (positive and negative) of oral azacitidine on the body and on the disease MDS, AML and CMML. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - 18 years or older. - Diagnosis of low or Int-1 risk MDS - Low platelet count, and/or low hemoglobin, and/or RBC transfusion-dependent and/or platelet transfusion-dependent - ECOG Performance status 0-2 - Standard safety inclusion for serum creatinine, AST, ALT, bilirubin. - Serum bicarbonate greater than or equal to 20 mEq/L. - Use of acceptable birth control. - Signed, written informed consent. Other eligibility criteria may apply. - Diagnosis of acute PML. - Previous or concurrent malignancy. - Prior treatment with azacitidine or other demethylating agents. - Treatment with any anticancer therapy or investigational drugs within 21 days. - Hypersensitivity to azacitidine or mannitol. - Presence of GI disease. - Active, uncontrolled infection. - Known Human Immunodeficiency Virus (HIV) or Hepatitis C, or known active viral Hepatitis B. - Breastfeeding or Pregnant females; - Presence of serious illness, medical condition, or other medical history which would be likely to interfere with a subject's participation in the study or with the interpretation of the results. - Current congestive heart failure (NY Heart Association Class III-IV), unstable angina or angina requiring surgical or medical intervention within 6 months, myocardial infarct within 6 months, or uncontrolled cardiac arrhythmia. Other exclusion criteria may apply. 995be30fce2cafcc0855b11d8aa42472 8612 Study of BHQ880 in Patients With High Risk Smoldering Multiple Myeloma II Bill Bensinger, MD 2482.00 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.8612.html http://www.clinicaltrials.gov/ct/search?term=NCT01302886 NCT01302886 Purpose This study will assess the antimyeloma effects of BHQ880A in patients with smoldering multiple myeloma with high risk of progression to active multiple myeloma. BHQ880 will be administered every 28 days in previously untreated patients. Disease assessments will be performed monthly and effects on bone metabolism will be assessed by measurement of serum and urine bone biomarkers, changes in BMD , and QCT with FEA. Additionally, the PK profile of BHQ880 as a single agent and following multiple doses will be obtained. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Confirmed diagnosis of SMM with high-risk for progression to multiple myeloma - BMPC = 10% and serum M-protein level = 3 g/dL, OR - BMPC = 10%, serum M-protein level < 3 g/dL, and an abnormal free light chain ratio of < 0.125 or > 8.0 - No previous or current anti-myeloma therapies - Patients = 18 years of age - Eastern Cooperative Oncology Group (ECOG) Performance status of 0 to 1 Other eligibility criteria may apply. - Previous treatment with IV bisphosphonates (i.e., pamidronate or zoledronic acid - Another primary malignant disease that requires systemic treatment - Concomitant Paget's disease of bone, uncorrected hyperparathyroidism, or uncontrolled thyroid disease - Clinically significant uncontrolled heart disease (e.g., unstable angina, congestive heart failure, uncontrolled hypertension, ventricular or atrial arrhythmias) - Treatment with an investigational product within 28 days before the first dose of study treatment - Pregnant or nursing (lactating) women - Women of child-bearing potential, UNLESS they are using two birth control methods. The two methods can be a double barrier method or a barrier method plus a hormonal method. - Other protocol-defined inclusion/exclusion criteria may apply Other exclusion criteria may apply. 9758ec4d477d07f87bee8ed1f6935e38 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 8651 IMA901 in Patients Receiving Sunitinib for Advanced/Metastatic Renal Cell Carcinoma III Scott Tykodi, MD 2496.00 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.8651.html http://www.clinicaltrials.gov/ct/search?term=NCT01265901 NCT01265901 The primary objective of the phase III study is to investigate whether IMA901 can prolong overall survival in patients with metastatic and/or locally advanced renal cell carcinoma (RCC) when added to standard first-line therapy with sunitinib. Secondary objectives include a subgroup analysis of overall survival in patients defined by a certain biomarker signature, the investigation of progression-free survival, best tumor response, safety, and immunological parameters. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both HLA type: HLA-A*02-positive Metastatic and/or locally advanced RCC with clear cell histology (histological confirmation by local pathologist required). NOTE: prior nephrectomy is NOT required. Measurable and/or non-measurable tumor lesions as per RECIST 1.1 Patients who are candidates for a first-line therapy with sunitinib. Favorable or intermediate risk according to the 6-score risk criteria in patients treated with VEGF-targeted agents according to Heng [Heng et al. 2009]. The patient has a favorable risk if none, or intermediate risk if one or two of the following criteria apply (if three or more criteria apply the patient is not eligible): - Hemoglobin < LLN, - Serum corrected calcium > ULN, - Karnofsky performance status < 80%, - Time from initial diagnosis to initiation of therapy < 1 year, - Absolute neutrophil count > ULN, - Platelets > ULN. Able to understand the nature of the study and give written informed consent. Willingness and ability to comply with the study protocol for the duration of the study. Female patients who are post menopausal (no menstrual period for a minimum of 1 year), or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) or practice a medically acceptable method of birth control. Male patients willing to use contraception (upon study entry and during the course of the study or have undergone vasectomy. Other eligibility criteria may apply. Prior systemic therapy for metastatic disease. (Note: prior adjuvant treatment for non-metastatic disease is allowed, however adjuvant therapy must have been stopped = 1 year before Visit C). History of or current brain metastases. Abnormal = CTC Grade 3 laboratory values for hematology (Hb, WBC, neutrophils, lymphocytes, platelets), liver (serum bilirubin, ALAT or ASAT) and renal function (serum creatinine). Metastatic second malignancy. Localized second malignancy expected to influence the patient's life span. Patients with a history or evidence of systemic autoimmune disease, e.g., rheumatoid arthritis, multiple sclerosis, systemic lupus erythematodes (SLE), scleroderma, Sjögren's syndrome, Wegener's granulomatosis, Guillain-Barre syndrome. Known active hepatitis B or C infection. Known HIV infection. Active infections requiring oral or intravenous antibiotics. Any other known infection with a biological agent that can cause a severe disease and poses a severe danger to lab personnel working on patients' blood or tissue. Received study drug within any clinical study (including approved and experimental drugs) within 4 weeks before sunitinib start. Serious intercurrent illness, which according to the investigator, poses an undue risk for the patient when participating in the trial, including, but not limited to, any of the following: - Clinically significant cardiovascular disease (e.g., uncontrolled hypertension; clinically significant cardiac arrhythmia, clinically significant QT-prolongation), - New York Heart Association class III-IV congestive heart failure, - Symptomatic peripheral vascular disease, - Severe pulmonary dysfunction, - Psychiatric illness or social situation that would preclude study compliance. Less than 12 months since any of the following: - Myocardial infarction, - Severe or unstable angina, - Coronary or peripheral artery bypass graft, - Cerebrovascular event incl. transient ischemic attack, - Pulmonary embolism / deep vein thrombosis (DVT). Pregnancy or breastfeeding. Any condition which in the judgment of the investigator would place the patient at undue risk or interfere with the results of the study. Other exclusion criteria may apply. 11039a1d30ff754b5a88aa1de87b79d3 8624 A Study of Escalating Doses of DCDS4501A in Patients With Relapsed or Refractory B-Cell Non Hodgkin's Lymphoma and Chronic Lymphocytic Leukemia I Oliver Press, MD, PhD 2501.00 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.8624.html http://www.clinicaltrials.gov/ct/search?term=NCT01290549 NCT01290549 Purpose This is a Phase I, multicenter, open-label, dose-escalation study of DCDS4501A administered as a single agent by IV infusion to patients with relapsed or refractory hematologic malignancies Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Life expectancy of at least 12 weeks - History of one of the following histologically-documented hematologic malignancy that is expected to express the CD79b antigen and for which no effective standard therapy exists: indolent non Hodgkin's lymphoma (NHL), Grade 3b FL, diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), or chronic lymphocytic leukemia (CLL) - All patients (NHL and B-CLL) must have at least one bi-dimensionally measurable lesion - For all men or women of childbearing potential (unless surgically sterile): use of adequate methods of contraception such as oral contraceptives, intrauterine device, or barrier method of contraception in conjunction with spermicidal jelly Other eligibility criteria may apply. - Prior use of any monoclonal antibody or antibody-drug conjugate within 4 weeks before Cycle 1, Day 1 - Treatment with radiotherapy, any chemotherapeutic agent, or treatment with any other investigational anti-cancer agent within 2 weeks prior to Cycle 1, Day 1. Adverse events from any previous treatments must be resolved or stabilized prior to Cycle 1, Day 1, except for neuropathy - Completion of autologous stem cell transplant within 100 days prior to Cycle 1, Day 1 - Prior allogeneic stem cell transplant Other exclusion criteria may apply. 117554266f3a0c0329ef26209a7abd11 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. - 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. d39980cdaef2f9a90b4e5ab20edc29a1 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. d906a2148cbfcd404387398bccb0ec6d 8722 A Study of GA101 (RO5072759) in Combination With Chemotherapy in Patients With Previously Untreated Chronic Lymphocytic Leukemia (GALTON) I John Pagel, MD, PhD 2514.00 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.8722.html http://www.clinicaltrials.gov/ct/search?term=NCT01300247 NCT01300247 This is an open-label, 2-arm, nonrandomized, multicenter, Phase Ib study to investigate the safety and efficacy of GA101 administered in combination with chemotherapy (FC or bendamustine regimens) in patients with previously untreated CD20-positive B-CLL. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Confirmed diagnosis of CD20-positive B-CLL - Rai Stage III/IV or Binet Stage C disease - Rai Stage I/II or Binet Stage B disease that requires treatment - Adequate baseline bone marrow function, unless there is clear evidence of extensive bone marrow involvement with tumor infiltration, myelodysplasia, or hypocellularity - No previous treatment for CLL by chemotherapy, radiotherapy, or immunotherapy - ECOG performance status of 0, 1, or 2 - Life expectancy of > 6 months Other eligibility criteria may apply. - Treatment with any other investigational agent or participation in another clinical trial within 28 days prior to the start of Cycle 1 - Transformation of CLL to aggressive B-cell malignancy - Creatinine clearance = 60 mL/min, calculated according to the formula of Cockroft and Gault - Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 times the upper limit of normal (ULN) - Total bilirubin = 3 x ULN - History of severe allergic or anaphylactic reactions to monoclonal antibody therapy - History of sensitivity to mannitol (if bendamustine is to be administered) - 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, including significant cardiovascular disease or pulmonary disease - Known active bacterial, viral, fungal, mycobacterial, or other infection (excluding fungal infections of nail beds) or any major episode of infection requiring treatment with IV antibiotics or hospitalization (related to the completion of the course of antibiotics) within 4 weeks before the start of Cycle 1 - Recent major surgery (within 4 weeks prior to the start of Cycle 1), other than for diagnosis - Known infection with human immunodeficiency virus (HIV) seropositive status - Presence of positive test results for hepatitis B (hepatitis B virus [HBV] surface antigen [HBsAg] and/or total hepatitis B core antibody [anti-HBc]) or hepatitis C (hepatitis C virus [HCV] antibody serology testing). Patients with chronic HBV infection, occult HBV infection, or past HBV infection will be excluded. Patients who have received IVIG within 3 months of enrollment and who are anti-HBc positive but HBV DNA negative will be considered for inclusion on the study by the Medical Monitor on a case-by-case basis. Patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA. - Women who are pregnant or lactating - Fertile men or women of childbearing potential unless 1) surgically sterile or 2) using an adequate measure of contraception such as oral contraceptives, intrauterine device, or barrier method of contraception in conjunction with spermicidal jelly - Concurrent (or within 7 days prior to the first dose of study treatment) systemic corticosteroid use except low-dose corticosteroid therapy used to treat an illness other than lymphoma Other exclusion criteria may apply. 94d479bfbd9b0b7e45b00c163993f256 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 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 8839 Study of Gemcitabine + PEGPH20 vs Gemcitabine Alone in Stage IV Previously Untreated Pancreatic Cancer I/II Sunil Hingorani, MD, PhD 2542.00 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.8839.html http://www.clinicaltrials.gov/ct/search?term=NCT01453153 NCT01453153 Purpose Phase 1B: Open label (all patients receive PEGPH20+gemcitabine), dose escalation, safety and tolerability study to determine the safe dose of PEGPH20 to use in combination with gemcitabine in Stage IV previously untreated pancreatic cancer patients. Phase 2: Randomized, double blind study to compare the effect of overall survival of gemcitabine plus PEGPH20 vs gemcitabine plus placebo in Stage IV previously untreated pancreatic cancer patients. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Patients with histologically confirmed Stage IV adenocarcinoma of the pancreas previously untreated for metastatic disease - One or more metastatic tumors measurable on CT scan per RECIST 1.1 criteria - Baseline CA19-9 of = 100 U/mL in the absence of biliary obstruction or other physiological process unrelated to the tumor that may cause an elevation in CA19-9 levels - Life expectancy of at least 3 months - Signed, written IRB/EC-approved informed consent - A negative serum pregnancy test, if female Other eligibility criteria may apply. - Known brain metastasis - New York Heart Association Class III or IV cardiac disease, myocardial infarction within the past 12 months, or cardiac arrhythmia requiring medical therapy - Active, uncontrolled bacterial, viral, or fungal infection requiring systemic therapy - Known allergy to hyaluronidase - Women currently pregnant or breast feeding Other exclusion criteria may apply. 01bddbf0f7d8f201bd8b325b2ea5d27a 7831 Efficacy and Safety of Zoledronic Acid ( Every 4 Weeks vs. Every 12 Weeks) in Patients With Documented Bone Metastases From Bone Cancer III Georgiana Ellis, MD 6979 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.7831.html http://www.clinicaltrials.gov/ct/search?term=NCT00320710 NCT00320710 Purpose Clinical trial in breast cancer patients with bone metastases pretreated with zoledronic acid. Looking at the effectiveness of giving zoledronic acid every 4 weeks versus every 12 weeks given over 1 year. This study is prospective, double-blind, stratified, multi-center, and two-arm. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Female - Female patients = 18 years of age - Confirmed breast cancer with bone metastasis. - Pretreated with Zometa®, or Aredia (pamidronate) or all sequential regimens of both, for a minimum of 9 doses. Other eligibility criteria may apply. - Abnormal kidney function determined by serum creatinine levels. - Current active dental problems including: ongoing infection of the teeth or jawbone; current exposed bone in the mouth; and current or prior diagnosis of osteonecrosis of the jaw. - Recent (within 8 weeks) or planned dental or jaw surgery (e.g., extraction, implants) - Diagnosis of metabolic bone disease other than osteoporosis (e.g., Paget's disease of bone) - Known hypersensitivity to Zometa - Treatment with other investigational drugs within 30 days prior to randomization. - Other protocol-defined exclusion criteria may apply. Other exclusion criteria may apply. be1698ad0a6c506e32bdcb10fdc77365 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 - Relapsed/refractory renal cell carcinoma, NSCLC, malignant melanoma, epithelial ovarian cancer, colorectal adenocarcinoma - Must have measurable disease Other eligibility criteria may apply. - No history of severe hypersensitivity reactions to other monoclonal antibodies or any agent affecting T cell activation - No prior therapy with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody - No active infection (viral, bacterial or fungal) - No active autoimmune disease or a documented history of autoimmune disease or history of syndrome that requires systemic steroids or immunosuppressive medications. - No active or latent infection Other exclusion criteria may apply. fe184ce2332a3026b4a65d013bebdfad 7878 A Study Of PF-04449913 In Select Hematologic Malignancies Or With Dasatinib In Chronic Myeloid Leukemia (CML) I Vivian Oehler, MD 7106 19; 36; 43 Chronic Myeloid Leukemia (CML); Hematologic Malignancies; Leukemia Phase 1 Program, Study Line phase1@u.washington.edu 206/288-7551 http://www.fhcrc.org/en/treatment/clinical-trials/detail.7878.html http://www.clinicaltrials.gov/ct/search?term=NCT00953758 NCT00953758 This study examines the effect of a small molecule inhibitor to the Sonic Hedgehog pathway on select hematologic malignancies. Part two of the study will examine the effect of this inhibitor in combination with dasatinib In Chronic Myeloid Leukemia. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - Patients with select advanced hematologic malignancies who are refractory, resistant or intolerant to prior therapies. They may be newly diagnosed and previously untreated, but not eligible for standard treatment options, or for whom standard therapies are not anticipated to result in a durable response. - ECOG performance status 0 to 2 - Adequate organ function Other eligibility criteria may apply. - Patients with active CNS disease - Patient with active malignancy with the exception of basal cell carcinoma, non melanoma skin cancer, carcinoma in situ cervical or skin cancer - Active GVHD other than Grade 1 skin involvement - Known malabsorption syndrome - Patient has an active, life threatening or clinically significant uncontrolled systemic infection Other exclusion criteria may apply. 3eeb433d492ca6107e03addfc7348063 8397 Immunotherapy Study for Surgically Resected Pancreatic Cancer III Andrew Coveler, MD 7259 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.8397.html http://www.clinicaltrials.gov/ct/search?term=NCT01072981 NCT01072981 Purpose The purpose of this study is to assess overall survival after treatment with a regimen of adjuvant therapy (Gemcitabine alone or with 5-FU chemoradiation) with or without HyperAcute®-Pancreas (algenpantucel-L) immunotherapy in subjects who have undergone surgical resection. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - A histological diagnosis of adenocarcinoma of the pancreas confirmed by pathology. Mixed subtypes of adenocarcinoma are acceptable as long as majority of cells are ductal adenocarcinoma. - American Joint Committee on Cancer (AJCC) Stage I or II Pancreatic carcinoma. Patients must have undergone surgical resection for the tumor and extent of resection must be either R0 (complete resection with grossly and microscopically negative margins of resection) or R1 (grossly negative but positive microscopically margins of resection). - Eastern Cooperative Oncology Group (ECOG) Performance Status = 2. - Serum albumin =2.0 gm/dL. - Expected survival =6 months. - Subjects must be able to take in adequate daily calorie intake based on judgment of clinical investigator. Adequate organ function including: - A. Marrow: white blood cells (WBC) =3000/mm3 and platelets =100,000/mm3. - B. Hepatic: serum total bilirubin =2 x ULN mg/dL, ALT (SGPT) and AST (SGOT) =3 x upper limit of normal (ULN). - C. Renal: serum creatinine (sCr) =2.0 x ULN, or creatinine clearance (Ccr) =30 mL/min. - First vaccination must be within 8 weeks after surgery. - Patients must have the ability to understand the study, its inherent risks, side effects and potential benefits and be able to give written informed consent to participate. Patients may not be consented by a durable power of attorney (DPA). - All subjects of child producing potential must agree to use contraception or avoidance of pregnancy measures while enrolled on study and receiving the experimental product, and for one month after the last immunization. Other eligibility criteria may apply. - Age <18-years-old. - Active metastases. Suspicious lesions on CT scans must be reviewed by a second, different reviewer. If active disease not ruled out by second reviewer, a positron emission tomography (PET) CT or further imaging tests or histology may be needed to rule out disease before enrollment is allowed. - Other malignancy within five years, unless the probability of recurrence of the prior malignancy is <5% as determined by the Principal Investigator based on available information. Patient's curatively treated for squamous and basal cell carcinoma of the skin or patients with a history of malignant tumor in the past that have been disease free for at least five years are also eligible for this study. - History of organ transplant. - Current, active immunosuppressive therapy such as cyclosporine, tacrolimus, etc. - Subjects taking chronic systemic corticosteroid therapy for any reason are not eligible. Subjects may receive steroids as prophylactic anti-emetics, not to exceed 10 mg Decadron weekly. Subjects may also receive pulse doses for Gemcitabine hypersensitivity, not to exceed Decadron 8 mg twice a day (BID) x 3 days prior to start day of Gemcitabine. Subjects receiving inhaled or topical corticosteroids are eligible. Subjects who require chronic systemic corticosteroids after beginning vaccination, will be removed from study. - Significant or uncontrolled congestive heart failure (CHF),myocardial infarction or significant ventricular arrhythmias within the last six months. - Active infection or antibiotics within 48 hours prior to study,including unexplained fever (temp > 38.1C). - Autoimmune disease (e.g., systemic lupus erythematosis (SLE), rheumatoid arthritis (RA), etc.). Patients with a remote history of asthma or mild active asthma are eligible. - Other serious medical conditions that may be expected to limit life expectancy to less than 2 years (e.g., liver cirrhosis) or a serious illness in medical opinion of the clinical investigator. - Any condition, psychiatric or otherwise, that would preclude informed consent, consistent follow-up or compliance with any aspect of the study (e.g., untreated schizophrenia or other significant cognitive impairment, etc.). - A known allergy to any component of the HyperAcute® immunotherapy. - Pregnant or nursing women due to the unknown effects of vaccination on the developing fetus or newborn infant. (For patients with child bearing potential, a ßHCG must be completed within 7 days of first vaccination). - Known HIV positive. Other exclusion criteria may apply. b66575d8221f427ba5fafbeddbdb986b 8465 Study for Women With Platinum Resistant Ovarian Cancer Evaluating EC145 in Combination With Doxil® (PROCEED) III Barbara Ann Goff, MD 7334 34; 65; 83 Gynecological Cancer; Ovarian Cancer; Solid Tumors Seattle Cancer Care Alliance Intake Office 800-804-8824 / 206-288-1024 http://www.fhcrc.org/en/treatment/clinical-trials/detail.8465.html http://www.clinicaltrials.gov/ct/search?term=NCT01170650 NCT01170650 The purpose of this study is to compare progression-free survival (PFS) (based upon investigator assessment using RECIST v1.1) in participants with platinum-resistant ovarian cancer who receive combination therapy with EC145 and pegylated liposomal doxorubicin (EC145+PLD) with that in participants who receive PLD and placebo. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Female Participants must sign an approved informed consent form (ICF). Participants must have pathology-confirmed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. Participants must have platinum-resistant ovarian cancer. Note that primary or secondary platinum resistance is allowed. Participants with primary platinumrefractory disease are not allowed. a. Primary platinum resistance is defined as disease that responded to primary platinum therapy and then progressed within 6 months of the last dose of primary platinum therapy. b. Secondary platinum resistance is defined as disease that responded to primary platinum therapy and subsequently progressed during or within 6 months of completing secondary platinum therapy (ie, last platinum dose). Participants must have at least a single (RECIST v1.1-defined) measurable lesion. For the purpose of obtaining a RECIST v1.1 baseline scan, participants must have a radiological evaluation conducted no more than 28 days prior to beginning study therapy (PLD). NOTE: For participants with a history of CNS metastasis, baseline radiological imaging must include an evaluation of the head. Participants with ovarian or fallopian tube cancer must have had prior debulking surgery. Participants must have received prior platinum-based chemotherapy for management of primary disease but must not have received more than 2 prior systemic cytotoxic regimens. Participants are allowed to have received, but are not required to have received, one additional non-cytotoxic antitumor agent (eg, biologic or cytostatic) for the management of ovarian cancer. Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Participants must have recovered (to baseline/stabilization) from prior cytotoxic therapy-associated acute toxicities. Participants must have adequate organ function including: 1. Bone Marrow Reserve: - Absolute neutrophil count (ANC) greater than or equat to 1.5x10^9/L prior to treatment. Participants on maintenance doses of granulocyte colony stimulating factor (G-CSF) are eligible. - Platelets greater than or equat to 100x10^9/L - Hemoglobin greater than or equat to 9 g/dL - Use of supportive care measures (eg, use of white blood cell [WBC] growth factors, antiemetics, epoetin) should follow the ASCO guidelines as listed at www.asco.org. Participants should receive full supportive care, including transfusion of blood as mandated by clinical need; however, transfusions administered for the sole purpose of meeting the study inclusion criteria between the time informed consent is signed and first dose of EC145/placebo/PLD is administered are not allowed. 2. Hepatic: Total bilirubin level < 1.5 x ULN and ALT, AST, GGT, and alkaline phosphatase levels < 2.5 x ULN. 3. Renal: Serum creatinine level less than or equal to 1.5 x ULN or for participants with serum creatinine levels above 1.5 x ULN, creatinine clearance greater than or equal to 50 mL/min/1.73m^2 4. Cardiac: Left ventricular ejection fraction (LVEF) equal to or greater than the institutional lower limit of normal. Other eligibility criteria may apply. Patients refractory to primary platinum therapy where "refactory" is defined as disease progression within 6 months of first dose of initial platinum-based therapy. Diagnosis of "tumor of low-malignant potential". Prior exposure to PLD or anthracycline therapy. Prior exposure to FR-targeted therapy (eg, EC145, EC0225, EC0489, farletuzumab). Prior therapy with vinorelbine (Navelbine®) or vinca-containing compounds. Prior abdominal or pelvic radiation therapy or radiation therapy to > 10% of the bone marrow at any time in the past or prior radiation therapy within the past 3 years to the breast/sternum, dermal lesions, head or neck. Recent (i.e., = 6 weeks) history of abdominal surgery or peritonitis Serious comorbidities (as determined by the investigator) such as, but not limited to, active congestive heart failure or recent myocardial infarction. Patients who require antifolate therapy for the management of comorbid conditions (e.g., rheumatoid arthritis) will be excluded from the trial. Pregnant or nursing. Concurrent malignancy requiring therapy (excluding non-invasive carcinoma or carcinoma in situ). Symptomatic central nervous system (CNS) metastasis. Other concurrent chemotherapy, immunotherapy, radiotherapy, 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). Use of low dose corticosteroid therapy (e.g., for nausea prophylaxis) is acceptable; however, concomitant tamoxifen therapy is not. Supportive care measures are allowed. Other exclusion criteria may apply. 39c360fcce4c0b5deea0741f3b086f28 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 Purpose This randomized phase I/II trial studies the side effects and best dose of Ampligen when given together with vaccine therapy and sargramostim (GM-CSF) to see how well it works in treating patients with stage II-IV human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Vaccines made from synthetic HER2/neu peptides may help the body build an effective immune response to kill tumor cells that express HER-2/neu. Our group has developed vaccines against the HER2 protein that create immune responses and in this study we are researching different ways that we may be able to make that immune response even better. Adjuvants are one way to help vaccines produce stronger immune responses. Our group has typically used the adjuvant GM-CSF and in this study we would like to look at another adjuvant called Ampligen. Giving vaccine therapy together with Ampligen and/or GM-CSF may be an effective treatment for breast cancer. Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both - 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: 1. No evidence of disease, or 2. Stable bone only disease after definitive therapy - Patients must have demonstrated HER2 positive disease, by one of the following methods: 1. Immunohistochemical (IHC) staining of 1+, 2+ or 3+ for the HER2 protein, or 2. 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. - 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. c13052b1e4b996315cb9b211e48e24df