Cyclophosphamide W/or W/Out Rituximab and Peripheral Stem Cell Transplantation in Patients With Recurrent Non-Hodgkin's Lymphoma
Condition: Lymphoma
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Monoclonal antibodies such as rituximab can locate cancer cells and either kill
      them or deliver cancer-killing substances to them without harming normal cells. Drugs used in
      chemotherapy use different ways to stop cancer cells from dividing so they stop growing or
      die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to
      give higher doses of chemotherapy drugs and kill more cancer cells. It is not yet known if
      combining rituximab with cyclophosphamide is more effective than cyclophosphamide alone in
      stimulating peripheral stem cells for transplantation.

      PURPOSE: This randomized phase II trial is studying how well giving cyclophosphamide with or
      without rituximab followed by chemotherapy and peripheral stem cell transplantation works in
      treating patients with recurrent non-Hodgkin's lymphoma.
    

Detailed description: 
      OBJECTIVES:

        -  Compare the effects of mobilization therapy with or without rituximab on hematopoietic
           stem cells, B and T lymphocytes, and natural killer cells in patients with advanced or
           recurrent B-cell non-Hodgkin's lymphoma.

        -  Compare the effects of B-lymphocyte purging using concurrent rituximab and mobilization
           therapy vs a CD34+ cell enrichment device on hematopoietic stem cells, B and T
           lymphocytes, and natural killer cells in the peripheral blood stem cell (PBSC)
           infusates.

        -  Compare the effect of these purging regimens on tumor cell content of PBSC infusates.

        -  Compare the effects of these regimens on myeloid and lymphoid engraftment after
           high-dose chemotherapy and autologous PBSC infusion in these patients.

        -  Compare post-transplantation infection complications in patients treated with these
           regimens.

        -  Compare the response and relapse-free survival of patients treated with these regimens.

      OUTLINE: This is a randomized study. Patients are randomized to 1 of 2 treatment arms.

        -  Arm I: Patients receive mobilization therapy comprising rituximab IV over 2-5 hours on
           days 1, 8, and 15 and cyclophosphamide IV over 3-6 hours on day 16. Beginning 36-48
           hours after the completion of cyclophosphamide, patients receive filgrastim (G-CSF)
           subcutaneously (SC) daily until blood counts recover. Patients then undergo peripheral
           blood stem cell (PBSC) collection.

      After completion of PBSC collection, patients receive high-dose chemotherapy comprising
      carmustine IV on days -7 to -3 and etoposide IV and cisplatin IV for 3 days during days -7 to
      -3. Patients may undergo involved-field radiotherapy to active or previously bulky (more than
      5 cm) tumors daily for 7-10 days.

      Patients receive unmanipulated PBSCs on day 0. Patients receive G-CSF SC daily beginning 4
      hours after completion of PBSC infusion and continuing until neutrophil engraftment.

        -  Arm II: Patients receive mobilization therapy comprising cyclophosphamide and G-CSF and
           high-dose chemotherapy comprising carmustine, etoposide, and cisplatin as in arm I.
           Patients may also undergo involved-field radiotherapy as in arm I. Patients receive CD34
           cell-enriched PBSC on day 0 followed by G-CSF as in arm I.

      Patients are followed every 3 months.

      PROJECTED ACCRUAL: A total of 71 patients will be accrued for this study within 2 years.
    

Intervention name(s): filgrastim; rituximab; carmustine; cisplatin; cyclophosphamide; etoposide; bone marrow ablation with stem cell support; peripheral blood stem cell transplantation; radiation therapy
Intervention type(s): Biological; Biological; Drug; Drug; Drug; Drug; Procedure; Procedure; Radiation
Intervention description(s): Beginning 36-48 hours after the completion of cyclophosphamide, patients receive filgrastim (G-CSF) subcutaneously (SC) daily until blood counts recover. Patients receive G-CSF SC daily beginning 4 hours after completion of PBSC infusion and continuing until neutrophil engraftment.; rituximab IV over 2-5 hours on days 1, 8, and 15; After completion of PBSC collection, patients receive high-dose chemotherapy comprising carmustine IV on days -7 to -3; After completion of PBSC collection, cisplatin IV for 3 days during days -7 to -3.; cyclophosphamide IV over 3-6 hours on day 16.; After completion of PBSC collection, etoposide IV for 3 days during days -7 to -3.; Patients then undergo peripheral blood stem cell (PBSC) collection.; Arm I: Patients receive unmanipulated PBSCs on day 0. Arm II: Patients receive CD34 cell-enriched PBSC on day 0.; Patients may undergo involved-field radiotherapy to active or previously bulky (more than 5 cm) tumors daily for 7-10 days.
Intervention MeSH terms: Cyclophosphamide; Carmustine; Rituximab; Etoposide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage III grade 1 follicular lymphoma; stage III grade 2 follicular lymphoma; stage III grade 3 follicular lymphoma; stage III adult diffuse small cleaved cell lymphoma; stage III adult diffuse mixed cell lymphoma; stage III adult diffuse large cell lymphoma; stage III adult immunoblastic large cell lymphoma; stage III adult lymphoblastic lymphoma; stage IV grade 1 follicular lymphoma; stage IV grade 2 follicular lymphoma; stage IV grade 3 follicular lymphoma; stage IV adult diffuse small cleaved cell lymphoma; stage IV adult diffuse mixed cell lymphoma; stage IV adult diffuse large cell lymphoma; stage IV adult immunoblastic large cell lymphoma; stage IV adult lymphoblastic lymphoma; recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent grade 3 follicular lymphoma; recurrent adult diffuse small cleaved cell lymphoma; recurrent adult diffuse mixed cell lymphoma; recurrent adult diffuse large cell lymphoma; recurrent adult immunoblastic large cell lymphoma; stage III mantle cell lymphoma; stage IV mantle cell lymphoma; recurrent mantle cell lymphoma