Chemotherapy Before Autologous Stem Cell Transplantation +/- Rituximab in Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma
Condition: Lymphoma
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin
Study type: Interventional
Phase: Phase 3

Summary: 
      RATIONALE: Drugs used in chemotherapy, such as dexamethasone, cisplatin, gemcitabine, and
      cytarabine, work in different ways to stop cancer cells from dividing so they stop growing or
      die. Combining chemotherapy with autologous stem cell transplantation may allow the doctor to
      give higher doses of chemotherapy drugs and kill more cancer cells. Monoclonal antibodies,
      such as rituximab, can locate cancer cells and either kill them or deliver cancer-killing
      substances to them without harming normal cells. Giving rituximab as maintenance therapy
      after stem cell transplantation may kill any remaining cancer cells. It is not yet known
      which salvage chemotherapy regimen is more effective before autologous stem cell
      transplantation in treating relapsed or refractory non-Hodgkin's lymphoma.

      PURPOSE: This randomized phase III trial is studying salvage chemotherapy using
      dexamethasone, cisplatin, and gemcitabine to see how well it works compared to dexamethasone,
      cisplatin, and cytarabine given before autologous stem cell transplantation in treating
      patients with relapsed or refractory aggressive non-Hodgkin's lymphoma. This trial also is
      studying giving rituximab as maintenance therapy to see how well it works compared to no
      further therapy after stem cell transplantation. Rituximab was added to both salvage
      treatment arms for CD20+ patients in a protocol amendment in 2005.
    

Detailed description: 
      OBJECTIVES:

      Salvage therapy

      Primary

        -  Compare the response rate and transplantation rate in patients with relapsed or
           refractory aggressive non-Hodgkin's lymphoma when treated with salvage chemotherapy
           comprising dexamethasone, cisplatin, and gemcitabine with or without rituximab vs a
           standard platinum-based regimen (dexamethasone, cisplatin, and high-dose cytarabine with
           or without rituximab).

        -  To compare the transplantation rates of the two protocol salvage regimens.

      Secondary

        -  Compare the event-free and overall survival of patients treated with these regimens.

        -  Compare the success rate of these regimens, in terms of getting patients to autologous
           stem cell transplantation and successful mobilization after high-dose chemotherapy.

        -  Compare the quality of life of patients treated with these salvage regimens.

        -  Compare the toxic effects of these salvage regimens in these patients.

        -  Compare resource utilization for patients treated with these salvage regimens.

        -  Compare relative medical and societal costs of these salvage regimens with outcomes in
           these patients.

      Maintenance therapy

      Primary

        -  Compare the 2-year event-free survival of patients with CD20+ B-cell lymphoma treated
           with maintenance rituximab after these salvage regimens and autologous stem cell
           transplantation to those patients who received no further treatment.

      Secondary

        -  Compare the 2-year survival of patients treated with or without maintenance rituximab.

        -  Compare the toxic effects of rituximab vs observation alone in these patients.

      OUTLINE: This is a randomized, multicenter study. For salvage therapy, patients are
      stratified according to participating center, International Prognostic Index score at
      relapse/study entry (0 or 1 vs 2 vs ≥ 3), immunophenotype (B cell vs T cell), response to or
      response duration after initial chemotherapy (no response or progressive disease vs > 1 year
      vs ≤ 1 year), and prior rituximab (yes vs no). For maintenance therapy, patients are
      stratified according to participating center, salvage therapy treatment randomization (with
      or without rituximab, cisplatin, dexamethasone, and gemcitabine vs with or without rituximab,
      cisplatin, dexamethasone, and cytarabine), response to salvage therapy (complete response
      [CR] and CR unconfirmed [CRu] vs partial response [PR] vs stable disease [SD]), and prior
      rituximab (yes vs no).

        -  Salvage therapy: Patients are randomized to 1 of 2 treatment arms.

             -  Arm I: Patients receive cisplatin IV over 60 minutes on day 1, dexamethasone IV or
                orally on days 1-4, and gemcitabine IV over 30 minutes on days 1 and 8. Patients
                with CD20+ B cell lymphoma receive rituximab IV over 1.5-6 hours on day 1.

             -  Arm II: Patients receive cisplatin IV over 24 hours on day 1, dexamethasone as in
                arm I, and cytarabine IV over 3 hours every 12 hours for a total of 2 doses on day
                2. Patients with CD20+ B cell lymphoma receive rituximab IV over 1.5-6 hours on day
                1.

      In both arms, treatment repeats every 21 days for at least 2 courses in the absence of
      disease progression or unacceptable toxicity.

      Patients are reassessed after 2 courses. Patients with progressive disease are removed from
      study. Patients with a CR, CRu, or PR proceed to autologous stem cell transplantation (ASCT).
      Patients with SD may proceed to ASCT or receive 1 additional course of salvage therapy at the
      discretion of the investigator. Patients receiving an additional course of salvage therapy
      are then reassessed after the completion of therapy. Patients with progressive disease are
      removed from study. Patients with a PR proceed to ASCT. Patients with SD may proceed to ASCT
      or be followed off study at the discretion of the investigator.

        -  ASCT: Responding patients (or those with stable disease, if that is the center's
           policy)undergo mobilization, stem cell harvest, and subsequent ASCT. Patients with CD20+
           B-cell disease are randomized to maintenance therapy or observation.

        -  Maintenance therapy: Patients are randomized to 1 of 2 treatment arms.

             -  Arm I: Beginning on day 28 posttransplantation, patients receive rituximab IV once
                every 2 months for 6 doses (a total of 12 months) in the absence of disease
                progression or unacceptable toxicity.

             -  Arm II: Patients undergo observation only. Quality of life is assessed at baseline,
                days 1 and 10 of course 2, day 1 of course 3 (if given), on the last day of salvage
                therapy (or the first day of mobilization, if given), and at 1 month
                posttransplantation.

      Patients who undergo ASCT are followed at months 1, 3, 7, 13, 19, and 25 and then annually
      thereafter. Patients who complete salvage therapy, but do not undergo ASCT are followed at
      months 4, 8, 14, 20, and 26 and then annually thereafter. Patients who relapse or progress
      are followed every 6 months until 25 months from ASCT or 26 months from completion of salvage
      therapy and then annually thereafter.

      PROJECTED ACCRUAL: A total of 637 patients will be accrued for this study within 3-4 years
      for the first randomization, and 240 transplanted CD20+ patients will be needed for the
      second randomization.
    

Intervention name(s): rituximab; cisplatin; cytarabine; dexamethasone; gemcitabine hydrochloride
Intervention type(s): Biological; Drug; Drug; Drug; Drug
Intervention description(s): Given IV; Given IV; Given IV; Given IV; Given IV
Intervention MeSH terms: Cytarabine; Dexamethasone; Rituximab; Gemcitabine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: anaplastic large cell lymphoma; recurrent adult Burkitt lymphoma; recurrent adult diffuse large cell lymphoma; angioimmunoblastic T-cell lymphoma