Stem Cell Transplantation With or Without Rituximab in Treating Patients With Relapsed or Progressive B-Cell Diffuse Large Cell Lymphoma
Condition: Lymphoma
MeSH terms: Lymphoma; Lymphoma, Large B-Cell, Diffuse
Study type: Interventional
Phase: Phase 3

Summary: 
      RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from
      dividing so they stop growing or die. Combining chemotherapy with stem cell transplantation
      may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.
      Monoclonal antibodies, such as rituximab, can locate tumor cells and either kill them or
      deliver tumor-killing substances to them without harming normal cells. It is not yet known
      whether stem cell transplantation is more effective with or without rituximab in treating
      relapsed or progressive B-cell diffuse large cell lymphoma.

      PURPOSE: Randomized phase III trial to compare the effectiveness of stem cell transplantation
      with or without rituximab in treating patients who have relapsed or progressive B-cell
      diffuse large cell lymphoma.
    

Detailed description: 
      OBJECTIVES:

        -  Compare disease-free survival of patients with relapsed or progressive B-cell diffuse
           large cell lymphoma undergoing stem cell transplantation with or without post-transplant
           rituximab.

        -  Evaluate the effect of rituximab, administered post-transplant, on the procedure-related
           mortality of these patients.

        -  Determine the potential infectious complications of the addition of this drug to
           autologous stem cell transplantation in these patients.

        -  Compare overall survival of patients treated with these regimens.

      OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
      relapse (relapsed more than 6 months after either initial complete remission [CR] or CR with
      positive positron emission tomography or MRI [gallium] vs failed to achieve initial CR or
      relapsed within 6 months after either initial CR or CR with positive PET or MRI [gallium])
      and prior rituximab (yes vs no).

      Stem cell mobilization

        -  Patients receive rituximab IV over 4-8 hours on days 1 and 5. Patients also receive
           cyclophosphamide IV over 2 hours on day 8 and filgrastim (G-CSF) subcutaneously (SC)
           beginning on day 9 and continuing until the last day of apheresis. Stem cells are
           collected over 1-3 days.

      Preparative regimen

        -  Regimen A (patients who have received prior radiotherapy or are ≥ 61 years of age):
           Patients receive carmustine IV over 2 hours on day -6, etoposide IV over 4 hours on day
           -4, and cyclophosphamide IV over 2 hours on day -2.

        -  Regimen B (all other patients): Patients undergo total body irradiation twice daily on
           days -8 to -5. Patients receive etoposide IV over 4 hours on day -4 and cyclophosphamide
           IV over 2 hours on day -2.

      Stem cells are reinfused on day 0. Patients are then randomized to one of two post-transplant
      treatment arms.

      Post-transplant treatment

        -  Arm I (rituximab): Patients receive G-CSF SC beginning on day 6 and continuing until
           blood counts recover. Patients receive rituximab IV over 4-8 hours every 7 days for 4
           doses, starting on day 45 post-transplant. Course of rituximab is repeated beginning on
           day 180 post-transplant.

        -  Arm II (no rituximab): Patients receive G-CSF as in arm I. Patients are followed for 10
           years.

      PROJECTED ACCRUAL: A total of 427 patients will be accrued for this study within 3.5 years.
    

Intervention name(s): filgrastim; rituximab; carmustine; cyclophosphamide; etoposide; peripheral blood stem cell transplantation; radiation therapy
Intervention type(s): Biological; Biological; Drug; Drug; Drug; Procedure; Radiation
Intervention MeSH terms: Cyclophosphamide; Carmustine; Rituximab; Etoposide
Allocation: Randomized
Primary purpose: Treatment
Keywords: recurrent adult diffuse large cell lymphoma