Donor Stem Cell Transplant in Treating Patients With High-Risk Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
|ClinicalTrials.gov Identifier: NCT01027000|
Recruitment Status : Active, not recruiting
First Posted : December 7, 2009
Results First Posted : May 3, 2017
Last Update Posted : June 12, 2017
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.
|Condition or disease||Intervention/treatment||Phase|
|Leukemia Lymphoma||Biological: rituximab Drug: busulfan Drug: cyclophosphamide Drug: fludarabine phosphate Drug: methotrexate Drug: sirolimus Drug: tacrolimus Procedure: allogeneic stem cell transplant||Phase 2|
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- To determine if this treatment can improve 2-year current progression-free survival (PFS) in the early disease cohort compared to historical controls. Specifically, we plan to study whether we can achieve 2-year PFS ≥ 70% and to exclude 2 year PFS ≤ 50%
- To determine whether in the advanced disease cohort we can achieve 2-year current PFS ≥ 50% and to exclude 2-year PFS ≤ 30%
- 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
- 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 to reduced intensity allogeneic stem cell transplant
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.
Patients are followed up periodically for a maximum of 5 years from study entry.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||68 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Study of Reduced-Intensity Allogeneic Stem Cell Transplant for High-Risk Chronic Lymphocytic Leukemia (CLL)|
|Study Start Date :||February 2010|
|Primary Completion Date :||January 2016|
Experimental: Treatment (Combination of chemotherapy and transplant)
See detailed description
|Biological: rituximab Drug: busulfan Drug: cyclophosphamide Drug: fludarabine phosphate Drug: methotrexate Drug: sirolimus Drug: tacrolimus Procedure: allogeneic stem cell transplant|
- 2-year Progression-free Survival in Early Disease Participants [ Time Frame: 2 years post-registration ]
Percentage of participants who were alive and progression free at 2 years for participants with early disease stage. The 2 year progression free survival, with 95% confidence interval, was estimated using the Kaplan Meier method.
A progression is defined as one of the following events:
- >= 50% increase in the products of at least two lymph nodes on two consecutive determinations two weeks apart (at least one lymph node must be >= 2 cm); appearance of new palpable lymph nodes.
- >= 50% increase in the size of the liver and/or spleen as determined by measurement below the respective costal margin; appearance of palpable hepatomegaly or splenomegaly, which was not previously present.
- > 50% increase in peripheral blood lymphocytes with an absolute increase > 5000/μL.
- Transformation to a more aggressive histology (i.e., Richter's syndrome or prolymphocytic leukemia with >= 56% prolymphocytes).
- Response [ Time Frame: 5 years post-registration ]
- Acute Graft-vs-host Disease (GVHD) [ Time Frame: 5 years post-registration ]
- Chronic GVHD [ Time Frame: 5 years post-registration ]
- Treatment-related Mortality [ Time Frame: 6 months post-transplant ]
- Overall Survival [ Time Frame: 5 years post-registration ]
- Chimerism for CD3 [ Time Frame: 5 years post-registration ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01027000
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|Study Chair:||Edwin P. Alyea, MD||Dana-Farber Cancer Institute|