Rituxan vs Bexxar When Combined With Carmustine, Etoposide, Cytarabine and Melphalan (BEAM) With Autologous Hematopoietic Stem Cell Transplantation (BMT CTN 0401)
|Lymphoma, B-Cell Lymphoma, Large-Cell, Immunoblastic Lymphoma, Non-Hodgkin||Drug: Autologous transplantation using rituxan/BEAM Drug: Autologous transplantation using Bexxar/BEAM||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase III Rituxan/BEAM vs. Bexxar/BEAM With Autologous Hematopoietic Stem Cell Transplantation (ASCT) for Persistent or Relapsed Chemotherapy Sensitive Diffuse Large B-cell Non-Hodgkin's Lymphoma (BMT CTN #0401)|
- Progression-free Survival (PFS) [ Time Frame: 1 and 2 years ]Patients are considered a failure for this endpoint if they die, relapse/progress, or receive anti-lymphoma therapy, other than post-transplant consolidative localized radiation (maximum 3 sites) to sites of prior bulk disease pre-transplant (> 3cm). The time to this event is the time from randomization until death, relapse/progression, receipt of anti-lymphoma therapy, or last follow up, whichever comes first.
- Overall Survival [ Time Frame: 1 and 2 years ]The event is death from any cause. The time to this event is the time from randomization to death or last follow-up. Surviving patients are censored at the time of last observation
- Incidence of Relapse/Progression [ Time Frame: 1 and 2 years ]The time to this event is measured from randomization. Deaths without relapse/progression are considered as a competing risk. Surviving patients with no history of relapse/progression are censored at time of last follow-up.
- Complete Response (CR) and Partial Response (PR) Proportion [ Time Frame: Day 100 and 2 years ]
- Platelet Recovery to 20,000 Cells/μL [ Time Frame: 100 and 180 days ]
- Hematologic Function [ Time Frame: 100 days, 1 year ]Hematologic function will be defined as ANC > 1,500 neutrophils/μL, hemoglobin > 10 g/dL without transfusion support, and platelet count > 100,000/μL without transfusion support.
- Incidence of Infection [ Time Frame: 1 year ]
- Mucositis Severity [ Time Frame: Day 21 ]Mucositis severity will be scored per the modified Oral Mucositis Assessment Scale (OMAS) scoring system on a scale of 0 - 4, where 0 equals normal mucosa and 4 equals severe mucosa.
- Immune Reconstitution [ Time Frame: 1 year ]Tests to be performed on peripheral blood include CD2, CD3, CD4, CD8, CD19, CD3+/CD25+, CD45 RA/RO, CD56+/CD3-.
- Immune Reconstitution of Quantitative Immunoglobulins [ Time Frame: 1 year ]Tests to be performed on peripheral blood for quantitative immunoglobulins include IgM, IgG and IgA.
- Treatment-related Mortality (TRM) [ Time Frame: 1 and 2 years ]TRM is defined as death occurring in a patient from causes other than relapse or progression
- Neutrophil Recovery [ Time Frame: Day 28 and Day 60 ]Time to neutrophil recovery will be the first of two consecutive days of > 500 neutrophils/μL following the expected nadir.
|Study Start Date:||December 2005|
|Study Completion Date:||August 2013|
|Primary Completion Date:||August 2013 (Final data collection date for primary outcome measure)|
Active Comparator: Rituxan/BEAM
Autologous transplantation using rituxan/BEAM
Drug: Autologous transplantation using rituxan/BEAM
Rituxan 375 mg/m2 (Day -19 and Day -12); BCNU 300 mg/m2 (Day -6); Etoposide (VP-16) 100 mg/m2 twice a day (Days -5 to -2); Cytarabine 100 mg/m2 twice a day (Days -5 to -2); Melphalan 140 mg/m2 (Day -1); Followed by autologous transplantation
Other Name: Rituximab
Autologous transplantation using Bexxar/BEAM
Drug: Autologous transplantation using Bexxar/BEAM
Bexxar dosimetric dose 5 mCi (Day -19); Bexxar therapy dose 75 cGy TBD (Day -12); BCNU 300 mg/m2 (Day -6); Etoposide (VP-16) 100 mg/m2 twice a day (Days -5 to -2); Cytarabine 100 mg/m2 twice a day (Days -5 to -2); Melphalan 140 mg/m2 (Day -1); Followed by autologous transplantation
Other Name: Tositumomab and Iodine I 131 Tositumomab Bexxar
Bexxar (Tositumomab and Iodine I 131 Tositumomab) is a radioimmunoconjugate with demonstrated anti-lymphoma effects. This drug is indicated for the treatment of patients with CD20 positive, relapsed or refractory, low grade, follicular, or transformed non-Hodgkin's lymphoma, including patients with Rituximab-refractory non-Hodgkin's lymphoma. Bexxar has been used in several Phase I and II transplant trials either alone or in combination with high-dose chemotherapy for the treatment of relapsed non-Hodgkin's lymphoma. The Phase I and II trials combining Bexxar with BEAM and autologous hematopoietic stem cell transplantation demonstrated promising early results with 80% event-free survival in relapsed chemosensitive diffuse large B-cell non-Hodgkin's lymphoma patients. The administration of Rituxan to the mobilization and conditioning regimen is now the standard of care at most transplant centers. Therefore, the primary endpoint of this study will be to compare progression-free survival after autologous hematopoietic stem cell transplantation for chemotherapy-sensitive diffuse large B-cell lymphoma using Rituxan/BEAM versus Bexxar/BEAM for pre-transplant conditioning.
All patients will receive induction or salvage chemotherapy as indicated by their clinical circumstance to achieve at least a partial response (as defined in the protocol). There must be 20% or less bone marrow involvement after their most recent salvage therapy.
Mobilization therapy may be employed per institutional guidelines, but all patients must receive one dose of rituxan (375 mg/m^2) at least within 4 weeks of actual stem cell apheresis. Patients must have an adequate autograft (target of at least 2.0 X 10^6 CD34+ cells/kg; minimum of more than 1.5 X 106 CD34+ cells/kg) to be eligible for the protocol. Eligible patients will be randomized to receive either: 1) Rituxan plus BEAM, with Rituxan 375 mg/m^2 IV Days -19 and -12, Carmustine (BCNU) 300 mg/m^2 Day -6, Etoposide 100 mg/m^2 Days -5 to -2, Cytarabine 100 mg/m^2 Days -5 to -2, and Melphalan 140 mg/m^2 Day -1 followed by ASCT; or, 2) Bexxar/BEAM with the dosimetric dose of 5 mCi Bexxar on Day -19 and the therapeutic dose calculated to administer 75 cGy total body dose (TBD) on Day -12. Patients will then receive BCNU 300 mg/m^2 Day -6, Etoposide 100 mg/m^2 Days -5 to -2, Cytarabine 100 mg/m^2 Days -5 to -2, and Melphalan 140 mg/m^2 Day -1 followed by ASCT.
Patients will be followed for 2 years post-transplant. Survival data, hematopoiesis data, incidence of infection, mucositis assessment data, immune reconstitution data, and toxicity data will be recorded and reported periodically to the BMT CTN Data Coordinating Center (DCC).
Please refer to this study by its ClinicalTrials.gov identifier: NCT00329030
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|Study Director:||Mary Horowitz, MD||Center for International Blood and Marrow Transplant Research|