Clinical trial NCT00946023
Conditions: Lymphoma B-cell Lymphoma Non Hodgkin Lymphoma Chronic Lymphocytic Leukemia
Keywords: lymphoma non hodgkin lymphoma allogeneic bone marrow transplantation nonmyeloablative cyclophosphamide rituximab
Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Start date: 2009-07-01; Completion date: 2013-07-17
Enrollment: 135 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
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.

Detailed description:
This phase II for relapsed or refractory B-cell malignancies builds on the platform of nonmyeloablative, related-donor, HLA (human leukocyte antigen)-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.

Arms: arm 1: Non-myeloablative allogeneic bone marrow transplant (BMT) with a fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD (graft vs host disease) prophylaxis. Rituximab will be given as post-transplant maintenance.
Interventions: intervention 1: Fludarabine intervention 2: Cyclophosphamide intervention 3: Total body irradiation intervention 4: Tacrolimus intervention 5: Mycophenolate Mofetil intervention 6: Rituximab intervention 7: Allogeneic Bone Marrow Transplant (BMT)
Intervention descriptions: intervention 1: Days -6 through -2: 30 mg/m\^2 IV daily intervention 2: Days -6 and -5: 14.5 mg/kg IV daily; Days 3 and 4: 50 mg/kg IV daily intervention 3: Day -1: 200 centigray (cGy) in a single fraction intervention 4: Start on Day 5 through Day 180 intervention 5: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day) intervention 6: Day 30 and every week after for 8 total doses: 375 mg/m\^2 IV intervention 7: Day 0: Donor bone marrow infusion

Protocol documents: