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| Sponsor: | Fred Hutchinson Cancer Research Center |
|---|---|
| Collaborators: |
National Cancer Institute (NCI) National Heart, Lung, and Blood Institute (NHLBI) |
| Information provided by: | Fred Hutchinson Cancer Research Center |
| ClinicalTrials.gov Identifier: | NCT00075478 |
Purpose
RATIONALE: Giving low doses of chemotherapy, such as fludarabine phosphate, and radiation therapy before a donor 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 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 transplant may stop this from happening. It is not yet known whether total-body irradiation (TBI) followed by donor stem cell transplant is more effective with or without fludarabine phosphate in treating hematologic cancer.
PURPOSE: This randomized phase III trial is studying TBI and fludarabine phosphate to see how it works compared with TBI alone followed by donor stem cell transplant in treating patients with hematologic cancer
| Condition | Intervention | Phase |
|---|---|---|
|
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Adult Acute Myeloid Leukemia With Del(5q) Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) Adult Acute Myeloid Leukemia With t(15;17)(q22;q12) Adult Acute Myeloid Leukemia With t(16;16)(p13;q22) Adult Acute Myeloid Leukemia With t(8;21)(q22;q22) Childhood Chronic Myelogenous Leukemia Childhood Myelodysplastic Syndromes Chronic Phase Chronic Myelogenous Leukemia Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue Nodal Marginal Zone B-cell Lymphoma Previously Treated Myelodysplastic Syndromes Recurrent Adult Acute Lymphoblastic Leukemia Recurrent Adult Acute Myeloid Leukemia Recurrent Adult Burkitt Lymphoma Recurrent Adult Diffuse Large Cell Lymphoma Recurrent Adult Diffuse Mixed Cell Lymphoma Recurrent Adult Diffuse Small Cleaved Cell Lymphoma Recurrent Adult Hodgkin Lymphoma Recurrent Adult Immunoblastic Large Cell Lymphoma Recurrent Adult Lymphoblastic Lymphoma Recurrent Childhood Acute Lymphoblastic Leukemia Recurrent Childhood Acute Myeloid Leukemia Recurrent Childhood Large Cell Lymphoma Recurrent Childhood Lymphoblastic Lymphoma Recurrent Childhood Small Noncleaved Cell Lymphoma Recurrent Grade 1 Follicular Lymphoma Recurrent Grade 2 Follicular Lymphoma Recurrent Grade 3 Follicular Lymphoma Recurrent Mantle Cell Lymphoma Recurrent Marginal Zone Lymphoma Recurrent Small Lymphocytic Lymphoma Recurrent/Refractory Childhood Hodgkin Lymphoma Refractory Chronic Lymphocytic Leukemia Refractory Multiple Myeloma Relapsing Chronic Myelogenous Leukemia Splenic Marginal Zone Lymphoma |
Procedure: total-body irradiation Drug: fludarabine phosphate Drug: mycophenolate mofetil Drug: cyclosporine Procedure: peripheral blood stem cell transplantation Other: laboratory biomarker analysis Other: flow cytometry Genetic: fluorescence in situ hybridization Genetic: polymerase chain reaction Genetic: cytogenetic analysis |
Phase III |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Multi-Center Phase III Study Comparing Nonmyeloablative Conditioning With TBI Versus Fludarabine/TBI for HLA-matched Related Hematopoietic Cell Transplantation for Treatment of Hematologic Malignancies |
| Estimated Enrollment: | 110 |
| Study Start Date: | October 2003 |
| Estimated Primary Completion Date: | October 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Arm I (chemotherapy, TBI, transplant, GVHD prophylaxis)
Patients receive fludarabine phosphate IV on days -4 to -2. Patients then undergo low-dose TBI on day 0. After TBI, patients undergo PBSCT on day 0. Patients receive cyclosporine PO BID on days -3 to 56 in the absence of GVHD. Patients with no evidence of GVHD at day 56 begin a cyclosporine taper and continue the taper until day 180. Patients with evidence of disease progression and no evidence of GVHD prior to day 56 receive tapered doses of cyclosporine for 2 weeks. Patients also receive MMF PO BID on days 0-28 in the absence of GVHD. If treatment for GVHD is required before day 28, MMF is continued until a steroid taper begins.
|
Procedure: total-body irradiation
Undergo TBI
Other Name: TBI
Drug: fludarabine phosphate
Given IV
Other Names:
Drug: mycophenolate mofetil
Given PO
Other Names:
Drug: cyclosporine
Given PO
Other Names:
Procedure: peripheral blood stem cell transplantation
Undergo transplantation
Other Names:
Other: laboratory biomarker analysis
Correlative studies
Other: flow cytometry
Correlative studies
Genetic: fluorescence in situ hybridization
Correlative studies
Other Name: fluorescence in situ hybridization (FISH)
Genetic: polymerase chain reaction
Correlative studies
Other Name: PCR
Genetic: cytogenetic analysis
Correlative studies
|
|
Active Comparator: Arm II (TBI, transplant, GVHD prophylaxis)
Patients undergo low-dose TBI on day 0. After TBI, patients undergo PBSCT on day 0. Patients receive cyclosporine PO BID on days -3 to 56 in the absence of GVHD. Patients with no evidence of GVHD at day 56 begin a cyclosporine taper and continue the taper until day 180. Patients with evidence of disease progression and no evidence of GVHD prior to day 56 receive tapered doses of cyclosporine for 2 weeks. Patients also receive MMF PO BID on days 0-28 in the absence of GVHD. If treatment for GVHD is required before day 28, MMF is continued until a steroid taper begins.
|
Procedure: total-body irradiation
Undergo TBI
Other Name: TBI
Drug: mycophenolate mofetil
Given PO
Other Names:
Drug: cyclosporine
Given PO
Other Names:
Procedure: peripheral blood stem cell transplantation
Undergo transplantation
Other Names:
Other: laboratory biomarker analysis
Correlative studies
Other: flow cytometry
Correlative studies
Genetic: fluorescence in situ hybridization
Correlative studies
Other Name: fluorescence in situ hybridization (FISH)
Genetic: polymerase chain reaction
Correlative studies
Other Name: PCR
Genetic: cytogenetic analysis
Correlative studies
|
PRIMARY OBJECTIVES:
I. To compare overall survival at 3 years after conditioning with 200 cGy TBI alone vs. fludarabine/200 cGy TBI in heavily pretreated patients with hematologic malignancies at low/moderate risk for graft rejection.
SECONDARY OBJECTIVES:
I. To compare the non-relapse mortality 1-year after conditioning in patients who received TBI alone vs. fludarabine/TBI.
II. To compare the incidences of graft rejection in patients who received TBI alone vs. fludarabine/TBI.
III. To compare the incidences of grades II-IV acute graft-versus-host disease (GVHD) and chronic extensive GVHD.
IV. To compare rates of disease progression and/or relapse-related mortality. V. To compare the immune reconstitution and the risks of infections.
OUTLINE:
NONMYELOABLATIVE CONDITIONING REGIMEN: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive fludarabine phosphate intravenously (IV) on days -4 to -2. Patients then undergo low-dose TBI on day 0.
ARM II: Patients undergo low-dose TBI on day 0.
ALLOGENEIC PERIPHERAL BLOOD STEM CELL TRANSPLANTATION (PBSCT): After TBI, patients undergo PBSCT on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine orally (PO) twice daily (BID) on days -3 to 56 in the absence of GVHD. Patients with no evidence of GVHD at day 56 begin a cyclosporine taper and continue the taper until day 180. Patients with evidence of disease progression and no evidence of GVHD prior to day 56 receive tapered doses of cyclosporine for 2 weeks. Patients also receive mycophenolate mofetil (MMF) PO BID on days 0-28 in the absence of GVHD. If treatment for GVHD is required before day 28, MMF is continued until a steroid taper begins.
Patients are followed up periodically for 1.5 years and then annually for 5 years post-transplantation.
Eligibility| Ages Eligible for Study: | up to 75 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contacts and Locations| United States, Oregon | |
| OHSU Cancer Institute-Southern Region | |
| Medford, Oregon, United States, 97504 | |
| United States, Utah | |
| LDS Hospital | |
| Salt Lake City, Utah, United States, 84143 | |
| University of Utah | |
| Salt Lake City, Utah, United States, 84112 | |
| United States, Washington | |
| Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | |
| Seattle, Washington, United States, 98109 | |
| VA Puget Sound Health Care System | |
| Seattle, Washington, United States, 98101 | |
| United States, Wisconsin | |
| Froedtert and the Medical College of Wisconsin | |
| Milwaukee, Wisconsin, United States, 53226 | |
| Germany | |
| Medizinische Univ Klinik Koln | |
| Koln, Germany, 50924 | |
| Universitaet Leipzig | |
| Leipzig, Germany, D-04103 | |
| University of Tuebingen-Germany | |
| Tuebingen, Germany, D-72076 | |
| Italy | |
| University of Torino | |
| Torino, Italy, 10126 | |
| Principal Investigator: | Brenda Sandmaier | Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium |
More Information
| Responsible Party: | Sandmaier, Brenda, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium |
| ClinicalTrials.gov Identifier: | NCT00075478 History of Changes |
| Other Study ID Numbers: | 1813.00, NCI-2009-01532, P01CA078902 |
| Study First Received: | January 9, 2004 |
| Last Updated: | August 19, 2011 |
| Health Authority: | United States: Institutional Review Board |
|
Congenital Abnormalities Burkitt Lymphoma Hodgkin Disease Leukemia Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Lymphoid Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Myeloid, Acute Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive Leukemia, Myeloid, Chronic-Phase Lymphoma Lymphoma, Follicular Lymphoma, Large B-Cell, Diffuse Lymphoma, Non-Hodgkin |
Multiple Myeloma Neoplasms, Plasma Cell Myelodysplastic Syndromes Preleukemia Lymphoma, B-Cell Lymphoma, Large-Cell, Immunoblastic Lymphoma, B-Cell, Marginal Zone Lymphoma, Mantle-Cell Epstein-Barr Virus Infections Herpesviridae Infections DNA Virus Infections Virus Diseases Tumor Virus Infections Neoplasms by Histologic Type Neoplasms |