Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 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 (0401)
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December 2005 – August 2013
May 31, 2012
December 8, 2016
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Commercial Use Data Restrictions No
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The BMT CTN 0401 trial compared 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.
Previous research has established the use of high-dose chemotherapy with autologous bone marrow transplantation as the standard of care for relapsed chemotherapy-sensitive diffuse large B-cell lymphoma (DLBCL). However, even in patients with chemotherapy-sensitive DLBCL, relapse of lymphoma is a major cause of transplantation failure. Bexxar (iodine I 131 tositumomab) is a radioimmunoconjugate 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 trials combining Bexxar with BEAM (chemotherapeutic agents carmustine, etoposide, cytarabine, and melphalan) and autologous hematopoietic stem cell transplantation demonstrated promising early results for event-free survival in relapsed chemosensitive DLBCL patients. The additional administration of monoclonal antibodies (rituximab) to the mobilization and conditioning regimen is the standard of care at most transplant centers. Therefore, the BMT CTN 0401 trial was initiated to test the primary hypothesis that the addition of 131 I-tositumomab to a standard high-dose chemotherapy transplantation regimen with BEAM would improve the 2-year progression-free survival compared with the addition of rituximab to the same chemotherapy transplantation protocol in patients with chemotherapy-sensitive persistent or relapsed DLBCL.
Enrolled patients were 18 to 80 years of age; had a Karnofsky score of at least 70, persistent or recurrent diffuse large B-cell lymphoma (DLBCL), and chemotherapy-sensitive disease; and had received one to three prior chemotherapy regimens. Eligible patients must have had persistent DLBCL after induction chemotherapy but were chemotherapy sensitive, experienced relapse after an initial complete response but had a partial response to salvage chemotherapy, or had a CR to salvage chemotherapy. Patients also needed ≤ 20% involvement of their bone marrow with lymphoma with no evidence of myelodysplastic syndrome in the pretransplantation bone marrow. All patients had their pathology reviewed locally and had a specimen that was CD20+ with no evidence of transformed follicular lymphoma. Patients were required to have an adequate autograft collection. A total of 224 patients were enrolled, with 113 patients randomly assigned to R-BEAM and 111 patients assigned to B-BEAM.
Enrolled patients were randomly assigned to treatment with rituximab and the BEAM regimen (R-BEAM) or Bexxar and the BEAM regimen (B-BEAM) with autologous hematopoietic stem cell transplantation infusion 24 hours later. The patients assigned to the B-BEAM arm received orally administered saturated solution of potassium iodide, two drops given three times daily starting one day before the dosimetric dose, and this was continued for 14 days after the therapeutic dose. Within 1 hour after the dosimetric dose of 131 I-tositumomab and before urination, a whole-body quantitative gamma camera image was obtained for baseline readings. Additional scans were performed on day 2, 3, or 4 and day 6 or 7 after the dosimetric dose. Using this information, the radioactive clearance from each patient was obtained to determine the radioactive millicurie activity of 131 I-tositumomab required to deliver the desired therapeutic dose 1 week later. Filgrastim 5 μg/kg was subcutaneously administered starting on day 5 and continued until neutrophil recovery of ≥ 500/μL for 3 consecutive days was obtained.
All patients were to receive induction or salvage chemotherapy as indicated by their clinical circumstance to achieve at least a partial response. Patients were to be followed for two years post-transplant. Survival data, hematopoiesis data, incidence of infection, mucositis assessment data, immune reconstitution data, and toxicity data were recorded.
The primary outcome was two-year progress-free survival (PFS) rates. PFS was defined as time to disease relapse or progression, initiation of nonprotocol antilymphoma therapy, or death. Secondary end points were overall survival, time to progression, complete response and partial response at day 100, relapse rates, time to hematologic recovery, incidence of grade 3 to 5 adverse events, maximum mucositis score on day 21 measured, 100-day treatment-related mortality, and the development of secondary myelodysplastic syndrome or acute myelogenous leukemia.
The B-BEAM and R-BEAM regimens produced similar 2-year progression-free survival and overall survival rates for patients with chemotherapy-sensitive relapsed diffuse large B-cell lymphoma. No differences in toxicities other than mucositis were noted.
J Clin Oncol. 2013 May 1;31(13):1662-8.
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Resources AvailableStudy Datasets Only
- Data Dictionary (PDF - 334.2 KB)
- Case Report Forms (PDF - 621.8 KB)
- Data Submission Documentation (PDF - 421.2 KB)
- Documentation for Outcomes Dataset (PDF - 609.2 KB)
- Protocol (PDF - 3.1 MB)
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