Rituximab and Combination Chemotherapy With or Without Radiation Therapy in Treating Patients With B-Cell 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 hydrochloride, 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. Radiation therapy uses high-energy x-rays to kill cancer cells. Giving
      rituximab and combination chemotherapy together with radiation therapy may kill more cancer
      cells. It is not yet known which schedule of rituximab and combination chemotherapy is more
      effective when given with or without radiation therapy in treating non-Hodgkin's lymphoma.

      PURPOSE: This randomized phase III trial is studying two different schedules of rituximab and
      combination chemotherapy with or without radiation therapy to compare how well they work in
      treating patients with aggressive B-cell non-Hodgkin's lymphoma.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Compare the time to treatment failure in patients with previously untreated, low-risk,
           aggressive, B-cell non-Hodgkin's lymphoma treated with 2 different schedules of
           immunochemotherapy comprising rituximab, cyclophosphamide, doxorubicin hydrochloride,
           vincristine, and prednisone with vs without radiotherapy.

      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 study center, serum lactic dehydrogenase level (≤ upper limit of normal [ULN] vs
      > ULN), disease stage (I or II vs III or IV), ECOG performance status (0-1 vs 2-3), bulky
      disease, and extranodal involvement. Patients with initial bulky disease and/or qualifying
      extranodal involvement are randomized to 1 of 4 treatment arms. Patients with non-bulky
      disease are randomized to treatment arms I or III.

      All patients will be 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 (R-CHOP-21): Patients receive R-CHOP immunochemotherapy comprising rituximab IV,
           cyclophosphamide IV over 15 minutes, doxorubicin IV, and vincristine IV on day 1 and
           oral prednisone once daily on days 1-5. Treatment repeats every 21 days for up to 6
           courses in the absence of disease progression or unacceptable toxicity.

        -  Arm II (R-CHOP-21 and radiotherapy): Patients receive R-CHOP as in arm I. Treatment
           repeats every 21 days for up to 6 courses in the absence of disease progression or
           unacceptable toxicity. Beginning 2-6 weeks after the last course of R-CHOP, patients who
           achieve a complete remission (CR) undergo radiotherapy 5 days a week for approximately
           5½ weeks.

        -  Arm III (R-CHOP-14): Patients receive R-CHOP as in arm I. Patients also receive
           filgrastim (G-CSF) subcutaneously once daily on days 4-13 or until blood counts recover.
           Treatment repeats every 14 days for up to 6 courses in the absence of disease
           progression or unacceptable toxicity.

        -  Arm IV (R-CHOP-14 and radiotherapy): Patients receive R-CHOP as in arm I. Patients also
           receive G-CSF an in arm III. Treatment repeats every 14 days for up to 6 courses in the
           absence of disease progression or unacceptable toxicity. Beginning 2-6 weeks after the
           last course of R-CHOP, patients who achieve CR undergo radiotherapy as in arm II.

      Patients in all arms undergo restaging of their disease after courses 3 and 6 of R-CHOP.
      Patients with stable disease after 6 courses or disease progression after courses 3 or 6
      proceed to salvage chemotherapy off study. Patients achieving a partial remission or an
      unconfirmed CR after 6 courses undergo additional restaging 4 weeks later. Patients with
      disease progression proceed to salvage chemotherapy off study. Patients who achieve CR after
      6 courses of R-CHOP or have a confirmed CR after the additional restaging undergo
      radiotherapy according to randomization (as above).

      After completion of study treatment, patients are followed periodically for 5 years and then
      annually thereafter.

      PROJECTED ACCRUAL: A total of 1,072 patients will be accrued for this study.
    

Intervention name(s): filgrastim; rituximab; cyclophosphamide; doxorubicin hydrochloride; prednisone; vincristine sulfate; radiation therapy
Intervention type(s): Biological; Biological; Drug; Drug; Drug; Drug; Radiation
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; stage III grade 3 follicular lymphoma; stage IV 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; stage III adult diffuse large cell lymphoma; stage III adult diffuse mixed cell lymphoma; stage IV adult diffuse large cell lymphoma; stage IV 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; stage III adult immunoblastic large cell lymphoma; stage IV 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; stage III adult Burkitt lymphoma; stage III mantle cell lymphoma; stage IV adult Burkitt lymphoma; stage IV 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