Clinical Trial: Rituxan vs Bexxar When Combined With Carmustine, Etoposide, Cytarabine and Melphalan (BEAM) With Autologous Hematopoietic Stem Cell Transplantation (BMT CTN 0401)

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

Brief 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 Summary:

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; mi
Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Current Primary Outcome: 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.


Original Primary Outcome: Progression-free survival (PFS) after autologous hematopoietic stem cell transplantation (ASCT) for chemotherapy-sensitive diffuse large B-cell lymphoma using Rituxan/BEAM versus Bexxar/BEAM for pre-transplant conditioning

Current Secondary Outcome:

  • 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.


Original Secondary Outcome:

  • Overall Survival
  • Time to progression
  • Complete response (CR) and partial response (PR) proportion at Day 100
  • Time to hematopoietic recovery
  • Hematologic function
  • Incidence of Infection
  • Maximum mucositis score by Day 21
  • Immune reconstitution
  • Treatment-related mortality
  • Development of myelodysplasia
  • Secondary acute myelogenous leukemia
  • Abnormal cytogenetics


Information By: National Heart, Lung, and Blood Institute (NHLBI)

Dates:
Date Received: May 22, 2006
Date Started: December 2005
Date Completion:
Last Updated: June 10, 2016
Last Verified: June 2016