S0213 Chemotherapy Plus Rituximab in Treating Patients With Mantle Cell Lymphoma
Condition: Lymphoma
MeSH terms: Lymphoma; Lymphoma, Mantle-Cell
Study type: Interventional
Phase: Phase 2

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. Combining rituximab with chemotherapy may kill more cancer cells.

      PURPOSE: Phase II pilot study to study the effectiveness of combining chemotherapy with
      rituximab in treating patients who have newly diagnosed mantle cell lymphoma.
    

Detailed description: 
      OBJECTIVES:

        -  Determine the 1-year progression-free survival probability in patients with previously
           untreated mantle cell lymphoma treated with courses of rituximab and cyclophosphamide,
           doxorubicin, vincristine, and dexamethasone alternating with courses of rituximab and
           high-dose cytarabine and methotrexate with leucovorin calcium.

        -  Determine the response rate (complete unconfirmed and complete and partial responses)
           and survival of patients treated with this regimen.

        -  Determine the toxicity of this regimen in these patients.

        -  Correlate chromosomal breakpoints, translocated immunoglobulin regulatory sequences, and
           cyclins D1, D2, and D3 with response and progression-free survival in patients treated
           with this regimen.

        -  Correlate gene expression (measured by DNA microarray analysis) with response and
           progression-free survival in patients treated with this regimen.

      OUTLINE: This is a pilot, multicenter study.

        -  Courses 1, 3, 5, and 7: Patients receive rituximab IV on day 1 (courses 1, 3, and 5
           only); cyclophosphamide IV over 3 hours twice a day on days 2-4; doxorubicin IV over 24
           hours on days 5-7; vincristine IV on days 5 and 12; dexamethasone orally or IV four
           times a day on days 2-5 and 12-15; and filgrastim (G-CSF) subcutaneously (SC) daily
           beginning on day 8 and continuing until blood counts recover.

        -  Courses 2, 4, 6, and 8: Patients receive rituximab IV on day 1 (courses 2, 4, and 6
           only); high-dose methotrexate IV over 24 hours on day 2; high-dose cytarabine IV over 2
           hours twice a day on days 3-4; oral leucovorin calcium 4 times a day on days 3-10; and
           G-CSF SC daily beginning on day 5 and continuing until blood counts recover.

      Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

      Patients are followed within 30 days, every 3 months for 2 years, and then every 6 months for
      3 years. Patients with disease progression are followed annually for up to 5 years from study
      entry.

      PROJECTED ACCRUAL: Approximately 50 patients will be accrued for this study within 25 months.
    

Intervention name(s): filgrastim; rituximab; cyclophosphamide; cytarabine; dexamethasone; doxorubicin; leucovorin; methotrexate; vincristine
Intervention type(s): Biological; Biological; Drug; Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): 5 ug/kg; 375 mg/m^2 on day 1 of cycles 1-6; 300 mg/m^2 on days 2-4 of cycles 1,3,5,7; 12 g/m^2 over days 3-4 of cycles 2,4,6,8; 40 mg on days 2-5 and 12-15 of cycles 1,3,5,7; 16.6 mg/m^2/day for days 5-7 of cycles 1,3,5,7; 170 mg over days 3-5 of cycles 2,4,6,8; 1000 mg/m^2 over days 2-3 of cycles 2,4,6,8; 1.4 mg/m^2 on days 5 and 12 of cycles 1,3,5,7
Other intervention name(s): G-CSF; cytoxan; Ara-C; adriamycin; leucovorin calcium; MTX; vincristine sulfate
Intervention MeSH terms: Leucovorin; Cytarabine; Dexamethasone; Cyclophosphamide; Rituximab; Doxorubicin; Methotrexate; Vincristine; Levoleucovorin
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage III mantle cell lymphoma; stage IV mantle cell lymphoma; contiguous stage II mantle cell lymphoma; noncontiguous stage II mantle cell lymphoma