Donor Stem Cell Transplant in Treating Patients With High-Risk Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
RATIONALE: Giving low doses of chemotherapy before a donor 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. Also, monoclonal antibodies, such as rituximab, can find cancer cells and either kill them or deliver cancer-killing substances to them without harming normal 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 tacrolimus, sirolimus, and methotrexate after the transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well donor stem cell transplant works in treating patients with high-risk chronic lymphocytic leukemia or small lymphocytic lymphoma.
Biological: anti-thymocyte globulin
Drug: fludarabine phosphate
Other: laboratory biomarker analysis
Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Procedure: peripheral blood stem cell transplantation
|Study Design:||Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study of Reduced-Intensity Allogeneic Stem Cell Transplant for High-Risk Chronic Lymphocytic Leukemia (CLL)|
- 2-year progression-free survival [ Designated as safety issue: No ]
- Response [ Designated as safety issue: No ]
- Acute graft-vs-host disease (GVHD) [ Designated as safety issue: No ]
- Chronic GVHD [ Designated as safety issue: No ]
- Treatment-related mortality [ Designated as safety issue: No ]
- Overall survival [ Designated as safety issue: No ]
- Chimerism for CD3 [ Designated as safety issue: No ]
|Study Start Date:||February 2010|
|Estimated Primary Completion Date:||February 2017 (Final data collection date for primary outcome measure)|
- To determine if reduced-intensity allogeneic stem cell transplantation can improve 2-year progression-free survival (PFS) of patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in the early disease cohort compared to historical controls.
- To determine whether 2-year PFS ≥ 50% can be achieved and 2-year PFS ≤ 30% can be excluded in patients with CLL or SLL in the advanced disease cohort.
- To assess objective response rate.
- To assess the incidence of grade 2-4 and 3-4 acute graft-vs-host disease (GVHD).
- To assess the incidence of extensive chronic GVHD.
- To assess the incidence of treatment-related mortality at 100 days and 1 year after transplantation.
- To assess overall survival.
- To assess donor chimerism for CD3+ cells at 1 and 2 years after transplantation.
- To investigate the presence of donor antigen-specific T-cell clones before and after withdrawal of immune suppression.
- To compare the relapse profiles of patients with T-cell responses against CLL to those whose CLL cells are not reactive.
- To prospectively examine the impact of high-risk genomic features and immune-based single nucleotide polymorphisms on response, toxicity, and 2-year PFS.
OUTLINE: This is a multicenter study.
Preparative regimen: Patients receive 1 of 2 preparative regimens at the discretion of the participating institution.
- Preparative regimen 1: Patients receive rituximab IV on days -7, -1, 7, and 14 and fludarabine phosphate IV over 30 minutes and busulfan IV over 3 hours on days -5 to -2. .
- Preparative regimen 2: Patients receive rituximab IV on days -7, -1, 7, and 14, fludarabine phosphate IV over 30 minutes on days -5 to -2, and cyclophosphamide IV over 1-2 hours on days -5 to -3. Patients with matched unrelated donors also receive anti-thymocyte globulin IV over 4-6 hours on days -6 to -4.
Graft-vs-host disease (GVHD) prophylaxis: Patients who receive preparative regimen 1 may receive either GVHD prophylaxis regimen 1 or 2; patients who receive preparative regimen 2 may only receive GVHD prophylaxis regimen 2.
- GVHD prophylaxis regimen 1: Patients receive tacrolimus either orally or IV and oral sirolimus beginning on day -2 and continuing until day 60, followed by a taper until day 180. Patients also receive methotrexate IV on days 1, 3, and 6.
- GVHD prophylaxis regimen 2: Patients receive tacrolimus either orally or IV beginning on day -2 and continuing until day 60, followed by a taper until day 180. Patients also receive methotrexate IV on days 1, 3, 6, and 11.
- Transplantation: Patients undergo allogeneic peripheral blood stem cell transplantation on day 0.
- Maintenance therapy: Patients receive rituximab IV at 3, 6, 9, and 12 months after transplantation.
Peripheral blood and bone marrow aspirate samples may be collected periodically for correlative laboratory studies.
After completion of study treatment, patients are followed up periodically for ≥ 5 years.