Rituxan/BEAM vs Bexxar/BEAM in Autologous Hematopoietic Stem Cell Transplant for Non-Hodgkin's Lymphoma (BMTCTN0401)
Condition: Lymphoma, B-Cell; Lymphoma, Large-Cell, Immunoblastic; Lymphoma, Non-Hodgkin
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma, Large-Cell, Immunoblastic; Plasmablastic Lymphoma
Study type: Interventional
Phase: Phase 3

Summary: 
      This study is designed as a Phase III, multicenter trial, comparing progression-free survival
      (PFS) after autologous hematopoietic stem cell transplantation using a standard Rituxan plus
      BEAM transplant regimen versus a regimen adding Bexxar to BEAM.
    

Detailed description: 
      BACKGROUND:

      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.

      DESIGN NARRATIVE:

      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).
    

Intervention name(s): Autologous transplantation using rituxan/BEAM; Autologous transplantation using Bexxar/BEAM
Intervention type(s): Drug; Drug
Intervention description(s): 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; 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 intervention name(s): Rituximab; Tositumomab and Iodine I 131 Tositumomab Bexxar
Intervention MeSH terms: Rituximab; Tositumomab I-131
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Large B-Cell Lymphoma; Non-Hodgkin's Lymphoma