Combination Chemotherapy With or Without Rituximab in 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 cancer cells
      and either kill them or deliver cancer-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 patients with non-Hodgkin's lymphoma.

      PURPOSE: This randomized phase III trial is studying four different combination chemotherapy
      regimens and rituximab to see how well they work compared to four different combination
      chemotherapy regimens alone in treating patients with non-Hodgkin's lymphoma.
    

Detailed description: 
      OBJECTIVES:

        -  Compare the time to treatment failure in patients with CD20-positive diffuse large
           B-cell non-Hodgkin's lymphoma treated with CHOP (cyclophosphamide, doxorubicin,
           vincristine, and prednisone)-like chemotherapy with vs without rituximab.

        -  Compare the tumor control, progression rate, and complete remission rate in patients
           treated with these regimens.

        -  Compare the disease-free and overall survival rate of patients treated with these
           regimens.

        -  Compare the toxicity of these regimens in these patients.

      OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified
      according to participating center, bulky disease (no vs yes), International Prognostic Index
      score (0 vs 1), and chemotherapy (CHOP vs CHOEP vs PMitCEBO vs MACOP-B). Patients are
      randomized to 1 of 2 treatment arms.

        -  Arm I: Patients receive 1 of the following chemotherapy regimens according to
           participating country:

             -  CHOP: Patients receive cyclophosphamide IV, doxorubicin IV, and vincristine IV on
                day 1 and oral prednisone or prednisolone on days 1-5. Treatment repeats every 21
                days for 6 courses in the absence of disease progression or unacceptable toxicity.

             -  CHOEP-21: Patients receive cyclophosphamide IV, doxorubicin IV, and vincristine IV
                on day 1; etoposide IV on days 1-3; and oral prednisone on days 1-5. Treatment
                repeats every 21 days for 6 courses in the absence of disease progression or
                unacceptable toxicity.

             -  PMitCEBO: Patients receive mitoxantrone IV, cyclophosphamide IV, and etoposide IV
                on day 1; vincristine IV and bleomycin IV on day 8; and oral prednisolone daily
                during weeks 1-4 and every other day during week 5. Treatment repeats every 14 days
                for 6 courses in the absence of disease progression or unacceptable toxicity.

             -  MACOP-B: Patients receive cyclophosphamide IV and doxorubicin IV on days 1, 15, 29,
                43, 57, and 71; methotrexate IV and vincristine IV on days 8, 36, and 64; bleomycin
                IV and vincristine IV on days 22, 50, and 78; and oral or intramuscular prednisone
                on days 1-84. Treatment continues in the absence of disease progression or
                unacceptable toxicity.

        -  Arm II: Patients receive arm I regimens (according to participating country) and
           rituximab as follows:

             -  CHOP and rituximab: Patients receive CHOP as in arm I and rituximab IV on day 1.

             -  CHOEP-21 and rituximab: Patients receive CHOEP-21 as in arm I and rituximab IV on
                day 1.

             -  PMitCEBO and rituximab: Patients receive PMitCEBO as in arm I and rituximab IV on
                day 1 during courses 1 and 4; on day 8 during courses 2 and 5; and on day 1 at 1
                and 4 weeks after completion of the last course of PMitCEBO chemotherapy.

             -  MACOP-B and rituximab: Patients receive MACOP-B as in arm I and rituximab IV on
                days 1, 22, 43, 64, 85, and 106.

      Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then
      annually thereafter.

      PROJECTED ACCRUAL: A total of 820 patients will be accrued for this study within
      approximately 2 years.
    

Intervention name(s): rituximab; CHOP regimen
Intervention type(s): Biological; Drug
Intervention description(s): Rituximab 375 mg/m² i.v. day 1; Cyclophosphamide 750 mg/m² i.v. day 1 Doxorubicin 50 mg/m² i.v. day 1 Vincristine 2 mg (abs.) i.v. day 1 Prednisone 100 mg/d p.o. days 1 to 5 Recycle day 22 Total number of cycles: 6
Intervention MeSH terms: Rituximab
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage I adult diffuse large cell lymphoma; contiguous stage II adult diffuse large cell lymphoma; noncontiguous stage II adult diffuse large cell lymphoma; stage III adult diffuse large cell lymphoma; stage IV adult diffuse large cell lymphoma