Optimized Donor Selection, Nonmyeloablative BMT for B-cell Lymphomas With Post-transplantation Cy and Rituximab
This phase II trial is studying how well giving fludarabine and cyclophosphamide together with total-body irradiation and rituximab works in treating patients with B-cell lymphoma or chronic lymphocytic leukemia who are undergoing an allogeneic (donor) bone marrow transplant. The type of bone marrow transplant is a less intensive or "mini" transplant using a relative as the bone marrow donor. The donated bone marrow stem cells may replace the patient's immune system cells and help destroy any remaining cancer (graft-versus-tumor effect). Patients undergoing this type of transplant often have more than one relative who could be a donor. The trial is also studying a new way of choosing amongst possible donors which might improve how the rituximab works.
Non Hodgkin Lymphoma
Chronic Lymphocytic Leukemia
Drug: Bone marrow transplantation
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Nonmyeloablative BMT With Post-transplant Cyclophosphamide, Rituximab and Optimized Donor Selection for B-cell Lymphomas|
- Event-free survival [ Time Frame: one year ] [ Designated as safety issue: No ]
- Longer-term event-free survival, overall survival, relapse, nonrelapse mortality, and incidence of acute and chronic graft versus host disease [ Time Frame: day 100, 1 year, 3 years ] [ Designated as safety issue: Yes ]
- Feasibility of selecting donors based on favorable Fc receptor polymorphism status [ Time Frame: four years ] [ Designated as safety issue: No ]
|Study Start Date:||July 2009|
|Estimated Study Completion Date:||August 2015|
|Primary Completion Date:||July 2013 (Final data collection date for primary outcome measure)|
Drug: Bone marrow transplantation
Nonmyeloablative conditioning regimen: Patients receive fludarabine IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 1-2 hours on days -6 and -5. Patients undergo total body irradiation on day -1.
Allogeneic bone marrow transplantation: Patients undergo donor bone marrow infusion on day 0.
Post-transplantation therapy: Patients receive cyclophosphamide IV over 1-2 hours on days 3 and 4. Beginning day 30, rituximab IV is administered once per week for 8 weeks.
Graft-vs-host disease prophylaxis: Beginning on day 5, patients receive oral mycophenolate mofetil until day 35 and tacrolimus (IV then changing to orally) until day 180.
This phase II for relapsed or refractory B-cell malignancies builds on the platform of nonmyeloablative, related-donor, HLA-matched or HLA-haploidentical BMT with post-transplantation high-dose cyclosphosphamide administered for prophylaxis of graft-versus-host disease and graft rejection. Rituximab is added to the transplant regimen with the goal of augmenting anti-tumor activity. In patients with B-cell lymphomas, specific polymorphisms in the immunoglobulin Fc receptor have been associated with greater sensitivity to rituximab or rituximab-based therapies, translating in some series into higher response rates and improved progression-free survival. This raises the possibility of selecting donors who carry this permissive polymorphism. This trial identifies and selects donors who have the favorable polymorphism at FcgammaR3A-158, thereby potentially conferring greater sensitivity to rituximab in the host after BMT.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00946023
|United States, Maryland|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins|
|Baltimore, Maryland, United States, 21231|
|Principal Investigator:||Yvette L Kasamon, MD||Sidney Kimmel Comprehensive Cancer Center|