Rituximab and Combination Chemotherapy in Treating Patients With Non-Hodgkin's Lymphoma
Condition: Lymphoma
MeSH terms: Lymphoma
Study type: Interventional
Phase: Phase 3

Summary: 
      RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different
      ways. Some find cancer cells and kill them or carry cancer-killing substances to them. Others
      interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy,
      such as cyclophosphamide, doxorubicin, vincristine, and prednisone, work in different ways to
      stop the growth of cancer cells, either by killing the cells or by stopping them from
      dividing. Giving rituximab together with combination chemotherapy may kill more cancer cells.
      It is not yet known which schedule of rituximab and combination chemotherapy is more
      effective in treating non-Hodgkin's lymphoma.

      PURPOSE: This randomized phase III trial is studying two different schedules of rituximab and
      combination chemotherapy to compare how well they work in treating patients with aggressive
      B-cell non-Hodgkin's lymphoma.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Compare the efficacy of 2 different schedules of immunochemotherapy comprising
           rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone in
           patients with previously untreated, low-risk, aggressive B-cell non-Hodgkin's lymphoma.

        -  Compare acute and chronic side effects in patients treated with these regimens.

        -  Compare time to treatment failure in patients treated with these regimens.

      Secondary

        -  Compare the time to progression in patients treated with these regimens.

        -  Compare the overall and disease-free/relapse-free survival of patients treated with
           these regimens.

        -  Compare the complete response rate in patients treated with these regimens.

        -  Compare the tumor control in patients treated with these regimens.

        -  Compare the safety of these regimens in these patients.

        -  Compare the pharmacoeconomics of these regimens.

        -  Compare patient adherence to these regimens.

      OUTLINE: This is an open-label, randomized, multicenter study. Patients are stratified
      according to participating center. Patients are randomized to 1 of 2 treatment arms.

      All patients are given the option of receiving a 1-week course of pretreatment therapy
      comprising vincristine IV once on day -6 and oral prednisone once daily on days -6 to 0.

        -  Arm I: Patients receive R-CHOP immunochemotherapy comprising rituximab IV,
           cyclophosphamide IV over 15 minutes, doxorubicin hydrochloride IV, and vincristine IV on
           day 1 and oral prednisone once daily on days 1-5. Treatment repeats every 21 days for 3
           courses in the absence of disease progression or unacceptable toxicity. Patients then
           undergo restaging of their disease. Patients with disease progression proceed to salvage
           therapy off study. All other patients receive 3 more courses of R-CHOP.

        -  Arm II: Patients receive R-CHOP as in arm I. Treatment repeats every 21 days for 3
           courses in the absence of disease progression or unacceptable toxicity. Patients then
           undergo restaging of their disease. Patients with disease progression proceed to salvage
           therapy off study. All other patients receive 1 more course of R-CHOP followed by 2
           courses of rituximab alone.

      All patients undergo final restaging after 6 courses of rituximab. Patients with disease
      progression, stable disease, or partial response proceed to salvage therapy off study.

      After completion of study treatment, patients are followed periodically for 5 years and then
      annually thereafter.

      PROJECTED ACCRUAL: A total of 622 patients will be accrued for this study.
    

Intervention name(s): rituximab; cyclophosphamide; doxorubicin hydrochloride; prednisone; vincristine sulfate
Intervention type(s): Biological; Drug; Drug; Drug; Drug
Intervention MeSH terms: Prednisone; Cyclophosphamide; Rituximab; Doxorubicin; Liposomal doxorubicin; Vincristine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: contiguous stage II grade 3 follicular lymphoma; noncontiguous stage II grade 3 follicular lymphoma; stage I grade 3 follicular lymphoma; contiguous stage II adult diffuse large cell lymphoma; contiguous stage II adult diffuse mixed cell lymphoma; noncontiguous stage II adult diffuse large cell lymphoma; noncontiguous stage II adult diffuse mixed cell lymphoma; stage I adult diffuse large cell lymphoma; stage I adult diffuse mixed cell lymphoma; nodal marginal zone B-cell lymphoma; anaplastic large cell lymphoma; contiguous stage II adult immunoblastic large cell lymphoma; noncontiguous stage II adult immunoblastic large cell lymphoma; stage I adult immunoblastic large cell lymphoma; contiguous stage II adult Burkitt lymphoma; contiguous stage II mantle cell lymphoma; noncontiguous stage II adult Burkitt lymphoma; noncontiguous stage II mantle cell lymphoma; stage I adult Burkitt lymphoma; stage I mantle cell lymphoma; contiguous stage II marginal zone lymphoma; noncontiguous stage II marginal zone lymphoma; stage I marginal zone lymphoma; stage III marginal zone lymphoma; stage IV marginal zone lymphoma; stage III adult Burkitt lymphoma; stage III adult diffuse large cell lymphoma; stage III adult diffuse mixed cell lymphoma; stage III adult immunoblastic large cell lymphoma; stage III grade 3 follicular lymphoma; stage III mantle cell lymphoma; stage IV adult Burkitt lymphoma; stage IV adult diffuse large cell lymphoma; stage IV adult diffuse mixed cell lymphoma; stage IV adult immunoblastic large cell lymphoma; stage IV grade 3 follicular lymphoma; stage IV mantle cell lymphoma