This randomized phase III trial is studying total-body irradiation (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. 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 TBI followed by donor stem cell transplant is more effective with or without fludarabine phosphate in treating hematologic cancer.
PRIMARY OBJECTIVES: I. To compare overall survival at 3 years after conditioning with 200 cGy TBI alone vs. fludarabine (fludarabine phosphate)/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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
87
Undergo TBI
Given IV
Given PO
Given PO
Undergo transplantation
OHSU Cancer Institute-Southern Region
Medford, Oregon, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, United States
LDS Hospital
Salt Lake City, Utah, United States
VA Puget Sound Health Care System
Seattle, Washington, United States
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States
Froedtert and the Medical College of Wisconsin
Milwaukee, Wisconsin, United States
Medizinische Univ Klinik Koln
Cologne, Germany
Universitaet Leipzig
Leipzig, Germany
University of Tuebingen-Germany
Tübingen, Germany
University of Torino
Torino, Italy
Overall Survival
Percentage of patients surviving as estimated by Kaplan-Meier.
Time frame: 3 years after transplant
Incidence of Non-relapse Mortality
Percentage of NRM as estimated by cumulative incidence methods with competing risks
Time frame: 3 years after transplant
Incidence of Relapse/Progression
Percentage of relapse estimated by cumulative incidence methods
Time frame: 3 years after transplant
Incidence of Relapse-related Mortality
Percentage of death following relapse/progression, estimated by cumulative incidence methods
Time frame: 3 years after transplant
Incidence of Grades II-IV Acute GVHD
Percentage patients with grades II-IV GHVD, estimated by cumulative incidence methods
Time frame: 120 days after transplant
Incidence of Chronic Extensive GVHD
Percentage patients with chronic extensive GVHD, estimated by cumulative incidence methods
Time frame: 3 years after transplant
Incidence of Graft Rejection
Donor CD3 chimerism less than 5%
Time frame: 1 year after transplant
Progression-free Survival
Percentage of patients with progression-free survival, estimated by cumulative incidence methods
Time frame: 3 years after transplant
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