Donor Stem Cell Transplant in Treating Patients With High-Risk Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
- Conditions
- LeukemiaLymphoma
- Interventions
- Biological: rituximabProcedure: allogeneic stem cell transplant
- Registration Number
- NCT01027000
- Lead Sponsor
- Alliance for Clinical Trials in Oncology
- Brief Summary
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.
- Detailed Description
OBJECTIVES:
Primary
* 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%
Secondary
* 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 68
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment (Combination of chemotherapy and transplant) rituximab See detailed description Treatment (Combination of chemotherapy and transplant) allogeneic stem cell transplant See detailed description Treatment (Combination of chemotherapy and transplant) busulfan See detailed description Treatment (Combination of chemotherapy and transplant) cyclophosphamide See detailed description Treatment (Combination of chemotherapy and transplant) fludarabine phosphate See detailed description Treatment (Combination of chemotherapy and transplant) methotrexate See detailed description Treatment (Combination of chemotherapy and transplant) sirolimus See detailed description Treatment (Combination of chemotherapy and transplant) tacrolimus See detailed description
- Primary Outcome Measures
Name Time Method 2-year Progression-free Survival in Early Disease Participants 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).
- Secondary Outcome Measures
Name Time Method Treatment-related Mortality 6 months post-transplant Acute Graft-vs-host Disease (GVHD) 5 years post-registration Overall Survival 5 years post-registration Chimerism for CD3 5 years post-registration Response 5 years post-registration Chronic GVHD 5 years post-registration
Trial Locations
- Locations (25)
Cleveland Clinic Taussig Cancer Center
🇺🇸Cleveland, Ohio, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Dana-Farber/Brigham and Women's Cancer Center
🇺🇸Boston, Massachusetts, United States
Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Tunnell Cancer Center at Beebe Medical Center
🇺🇸Lewes, Delaware, United States
Cancer Institute of New Jersey at Cooper - Voorhees
🇺🇸Voorhees, New Jersey, United States
CCOP - Christiana Care Health Services
🇺🇸Newark, Delaware, United States
UNMC Eppley Cancer Center at the University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Oklahoma University Cancer Institute
🇺🇸Oklahoma City, Oklahoma, United States
City of Hope Comprehensive Cancer Center
🇺🇸Duarte, California, United States
University of Chicago Cancer Research Center
🇺🇸Chicago, Illinois, United States
Union Hospital of Cecil County
🇺🇸Elkton, Maryland, United States
Holden Comprehensive Cancer Center at University of Iowa
🇺🇸Iowa City, Iowa, United States
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
🇺🇸Saint Louis, Missouri, United States
Monter Cancer Center of the North Shore-LIJ Health System
🇺🇸Lake Success, New York, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
CCOP - North Shore University Hospital
🇺🇸Manhasset, New York, United States
Don Monti Comprehensive Cancer Center at North Shore University Hospital
🇺🇸Manhasset, New York, United States
Long Island Jewish Medical Center
🇺🇸New Hyde Park, New York, United States
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
New York Weill Cornell Cancer Center at Cornell University
🇺🇸New York, New York, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
🇺🇸Tampa, Florida, United States
Florida Hospital Cancer Institute at Florida Hospital Orlando
🇺🇸Orlando, Florida, United States
Wake Forest University Comprehensive Cancer Center
🇺🇸Winston-Salem, North Carolina, United States