Combination Chemotherapy With or Without Rituximab in Treating Older Patients With Non-Hodgkin's Lymphoma
Condition: Lymphoma
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin
Study type: Interventional
Phase: Phase 3

Summary: 
      RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing
      so they stop growing or die. 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 combination chemotherapy is more effective with or without
      rituximab in treating aggressive non-Hodgkin's lymphoma.

      PURPOSE: This randomized phase III trial is studying how well giving cyclophosphamide,
      doxorubicin, vincristine, and prednisone together with or without rituximab works in treating
      older patients who have aggressive non-Hodgkin's lymphoma. (This trial is no longer
      randomized as of 6/2005).
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Compare the efficacy of cyclophosphamide, doxorubicin, vincristine, and prednisone
           (CHOP) with vs without rituximab in elderly patients with aggressive non-Hodgkin's
           lymphoma.

        -  Compare the efficacy of 6 vs 8 courses of CHOP chemotherapy in patients treated with
           these regimens.

        -  Compare the rate of complete remission, rate of primary progression, tumor control,
           disease-free survival, overall survival, and relapse after radiotherapy in patients
           treated with these regimens.

        -  Compare the safety and side effects of these regimens in these patients.

      Secondary

        -  Compare short-term and long-term side effects of these regimens in these patients.

        -  Compare quality of life of patients treated with these regimens.

        -  Compare the cost of these regimens in these patients.

        -  Determine relapse in patients treated with these regimens who received involved-field
           radiotherapy.

      OUTLINE: This is a randomized (randomized part of study completed as of 6/2005), open-label,
      multicenter study. Patients are stratified according to participating center, value for serum
      lactic dehydrogenase (no greater than upper limit of normal [ULN] vs greater than ULN), bulky
      disease present (no vs yes), stage (I or II vs III or IV), general ECOG status of patient (0
      or 1 vs 2), and age (61 to 70 vs 71-80). Patients are randomized to 1 of 4 treatment arms.
      Patients with CD20-negative lymphoma are randomized to arms I or II only.

        -  Prephase treatment:Patients receive vincristine IV on day -6 and prednisone on day -6 to
           day 0 before initiating CHOP chemotherapy.

        -  Arm I (closed to accrual as of 7/25/2005): Patients receive standard CHOP chemotherapy
           comprising cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1 and oral
           prednisone on days 1-5. Patients also receive filgrastim (G-CSF) subcutaneously once
           daily on days 6-12 of each CHOP course. Treatment repeats every 2 weeks for 6 courses.

        -  Arm II (closed to accrual as of 7/25/2005): Patients receive standard CHOP chemotherapy
           and G-CSF as in arm I for a total of 8 courses.

        -  Arm III: Patients receive standard CHOP chemotherapy and G-CSF as in arm I. Patients
           also receive rituximab IV before CHOP every 2 weeks for a total of 8 courses.

        -  Arm IV (closed to accrual as of 7/25/2005): Patients receive standard CHOP chemotherapy
           and G-CSF as in arm II. Patients also receive rituximab IV before CHOP every 2 weeks for
           a total of 8 courses.

      In all arms, treatment continues in the absence of disease progression or unacceptable
      toxicity.

      Beginning 3-6 weeks after completion of the last chemotherapy course, after complete recovery
      of bone marrow, and after complete remision of mucositis, patients with sites of initial
      bulky disease or extranodal involvement undergo radiotherapy 5 times a week for 4 weeks.

      Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then
      annually thereafter.

      PROJECTED ACCRUAL: Approximately 1580 patients will be accrued for this study within 5 years.
    

Intervention name(s): filgrastim; rituximab; CHOP regimen; cyclophosphamide; doxorubicin hydrochloride; prednisone; vincristine sulfate; radiation therapy
Intervention type(s): Biological; Biological; Drug; Drug; Drug; Drug; Drug; Radiation
Intervention description(s): 36Gy on BULK and extranodal involvement
Intervention MeSH terms: Prednisone; Cyclophosphamide; Rituximab; Doxorubicin; Liposomal doxorubicin; Vincristine
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: anaplastic large cell lymphoma; angioimmunoblastic T-cell lymphoma; stage III grade 1 follicular lymphoma; stage III grade 3 follicular lymphoma; stage III grade 2 follicular lymphoma; stage I adult T-cell leukemia/lymphoma; stage II adult T-cell leukemia/lymphoma; stage III adult T-cell leukemia/lymphoma; stage IV adult T-cell leukemia/lymphoma; contiguous stage II adult lymphoblastic lymphoma; noncontiguous stage II adult lymphoblastic lymphoma; stage I adult lymphoblastic lymphoma; stage III adult lymphoblastic lymphoma; stage IV adult lymphoblastic lymphoma; contiguous stage II adult diffuse large cell lymphoma; noncontiguous stage II adult diffuse large cell lymphoma; stage I adult diffuse large cell lymphoma; stage III adult diffuse large cell lymphoma; stage IV adult diffuse large cell lymphoma; contiguous stage II mantle cell lymphoma; noncontiguous stage II mantle cell lymphoma; stage I mantle cell lymphoma; stage III mantle cell lymphoma; stage IV mantle cell lymphoma; contiguous stage II adult Burkitt lymphoma; noncontiguous stage II adult Burkitt lymphoma; stage I adult Burkitt lymphoma; stage III adult Burkitt lymphoma; stage IV adult Burkitt lymphoma; contiguous stage II marginal zone lymphoma; noncontiguous stage II marginal zone lymphoma; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; nodal marginal zone B-cell lymphoma; splenic marginal zone lymphoma; stage I marginal zone lymphoma; stage III marginal zone lymphoma; stage IV marginal zone lymphoma