Fludarabine Phosphate and Total-Body Irradiation Before Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Leukemia
This clinical trial studies how well giving fludarabine phosphate together with total-body irradiation (TBI) before donor peripheral blood stem cell transplant works in treating patients with chronic lymphocytic leukemia or small lymphocytic leukemia. 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. Giving chemotherapy before or after peripheral blood stem cell 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 before and after the transplant may stop this from happening
B-cell Chronic Lymphocytic Leukemia
Contiguous Stage II Small Lymphocytic Lymphoma
Noncontiguous Stage II Small Lymphocytic Lymphoma
Recurrent Small Lymphocytic Lymphoma
Refractory Chronic Lymphocytic Leukemia
Stage I Chronic Lymphocytic Leukemia
Stage I Small Lymphocytic Lymphoma
Stage II Chronic Lymphocytic Leukemia
Stage III Chronic Lymphocytic Leukemia
Stage III Small Lymphocytic Lymphoma
Stage IV Chronic Lymphocytic Leukemia
Stage IV Small Lymphocytic Lymphoma
Drug: fludarabine phosphate
Drug: mycophenolate mofetil
Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Procedure: hematopoietic stem cell transplantation
Other: flow cytometry
Genetic: polymerase chain reaction
Radiation: total-body irradiation
Other: laboratory biomarker analysis
Procedure: bone marrow aspiration
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Allogeneic Hematopoietic Stem Cell Transplantation With Nonmyeloablative Conditioning for Patients With Chronic Lymphocytic Leukemia - a Multi-Center Trial|
- Survival using a non-myeloablative conditioning regimen with HSCT in patients with fludarabine phosphate-refractory CLL [ Time Frame: At 18 months ] [ Designated as safety issue: No ]
- Acute grade II-IV GVHD and chronic GVHD [ Time Frame: At day 84 ] [ Designated as safety issue: No ]
- Transplant-related mortality [ Time Frame: At 200 days ] [ Designated as safety issue: No ]Defined as death before day +100 not related to progression of disease.
|Study Start Date:||March 2003|
|Estimated Primary Completion Date:||June 2017 (Final data collection date for primary outcome measure)|
Experimental: Treatment (enzyme inhibitor, transplant, GVHD prophylaxis)
NONMYELOABLATIVE CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and TBI on day 0. TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant on day 0. GVHD PROPHYLAXIS: Patients receive cyclosporine PO every 12 hours on days -3 to 180 with taper on day 56 and mycophenolate mofetil PO every 12 hours on days 0-27.
Drug: fludarabine phosphate
Other Names:Drug: cyclosporine
Other Names:Drug: mycophenolate mofetil
Other Names:Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Undergo allogeneic peripheral blood stem cell transplantProcedure: hematopoietic stem cell transplantation
Undergo allogeneic peripheral blood stem cell transplant
Other Name: Stem Cell TransplantationOther: flow cytometry
Correlative studiesGenetic: polymerase chain reaction
Other Name: PCRRadiation: total-body irradiation
Other Name: TBIOther: laboratory biomarker analysis
Correlative studiesProcedure: bone marrow aspiration
I. To determine whether nonmyeloablative allogeneic hematopoietic stem cell transplantation (HSCT) from matched-related donors can improve the probability of survival 18 months after treatment for fludarabine (fludarabine phosphate)-refractory, fludarabine phosphate, cyclophosphamide, and rituximab (FCR)-failed, or del 17p chronic lymphocytic leukemia (CLL) beyond that observed in historical controls (30%).
I. To assess the rate of relapse with allogeneic HSCT using nonmyeloablative conditioning for patients with fludarabine-refractory, FCR-failed, or del 17p CLL compared with historical data on autologous HSCT.
II. To estimate the incidence of grade 2-4 acute graft-versus-host disease (GVHD) and chronic GVHD in patients with CLL treated with low-dose TBI, fludarabine, PBSC infusion and immunosuppression with cyclosporine and mycophenylate mofetil.
III. To characterize the rate and types of infections with this regimen. IV. To estimate the rate of transplant-related mortality in the first 200 days.
NONMYELOABLATIVE CONDITIONING: Patients receive fludarabine phosphate intravenously (IV) on days -4 to -2 and TBI on day 0.
TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant on day 0.
GVHD PROPHYLAXIS: Patients receive cyclosporine orally (PO) every 12 hours on days -3 to 180 with taper on day 56 and mycophenolate mofetil PO every 12 hours on days 0-27.
After completion of study treatment, patients are followed up at 12 and 18 months, and then annually thereafter for 5 years.
|United States, Washington|
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|
|Seattle, Washington, United States, 98109|
|Veterans Administration Center-Seattle|
|Seattle, Washington, United States, 98108|
|University of Torino|
|Torino, Italy, 10126|
|Principal Investigator:||David Maloney||Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|