Rituximab and Combination Chemotherapy in Treating Older Patients With Previously Untreated B-Cell Lymphoma
Condition: Lymphoma
MeSH terms: Lymphoma
Study type: Interventional
Phase: Phase 2

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.

      PURPOSE: This phase II trial is studying how well giving rituximab together with combination
      chemotherapy works in treating older patients with previously untreated B-cell lymphoma.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Determine a pharmacokinetic profile for pharmacokinetics-based or rituximab within a
           CHOP-14 regimen comprising cyclophosphamide, doxorubicin hydrochloride, vincristine, and
           prednisone in elderly patients with previously untreated aggressive B-cell lymphoma.

        -  To determine whether increased single-doses of rituximab for males can compensate their
           lower serum levels.

        -  Evaluate the safety and toxicity profile of this regimen in male patients.

      Secondary

        -  Determine the rate of complete responses, primary progressions under therapy, event-free
           survival, progression-free survival, and overall survival in patients treated with this
           regimen.

        -  Determine the rate of primary progression in patients treated with this regimen.

      OUTLINE: This is a multicenter study. All patients undergo the following treatment.

        -  Prephase treatment: Patients receive vincristine subcutaneously on day -6 and oral
           prednisone on days -6 to 0.

        -  Immunochemotherapy and radiotherapy: Patients receive CHOP chemotherapy comprising
           cyclophosphamide IV over 15 minutes, doxorubicin hydrochloride IV, and vincristine IV on
           day 1 and oral prednisone once daily on days 1-5. Patients also receive pegfilgrastim
           subcutaneously on days 4, 18, 32, 46, 60, and 74. Treatment with CHOP chemotherapy
           repeats every 14 days for up to 6 courses in the absence of disease progression or
           unacceptable toxicity. Patients who show no response after course 4 of CHOP chemotherapy
           proceed to salvage chemotherapy off study.

      Patients are evaluated 2-4 weeks after completion of CHOP. Patients with initial bulky
      disease (i.e., diameter ≥ 7.5 cm) or extranodal involvement AND achieving complete remission
      (CR), unconfirmed CR (CRu), or partial remission undergo radiotherapy 5 days a week for 4
      weeks. Patients who do not achieve CR or CRu 2 months after completion of radiotherapy
      proceed to salvage chemotherapy off study.

      Patients are then stratified according to center, International Prognostic Index (1-2 vs
      3-5), disease involvement (bulky vs extranodal vs bulky and/or extranodal), age (61-70 years
      old vs 71-80 years old), and gender. Patients are randomized to 1 of 2 treatment arms.

        -  Arm I (2-weekly rituximab): Patients receive rituximab IV 375 mg/m^2 (females) and 500
           mg/m^2 (males) over 4 hours on days 0, 14, 28, 42, 56, 70, 84, and 98. Patients also
           receive pegfilgrastim subcutaneously on day 4 of each course.

        -  Arm II (pharmacokinetic-based dose-dense rituximab): Patients receive rituximab IV 375
           mg/m^2 (females) and 500 mg/m^2 (males) over 4 hours on days -1, 0, 3, 7, 14, 21, 28,
           and 42. Patients also receive pegfilgrastim subcutaneously on day 4 of each course.

      Some patients undergo blood sample collection periodically during and after treatment for
      pharmacokinetic studies.

      After completion of study treatment, patients are followed every 3 months for 2 years, every
      6 months for 3 years, and then once a year therafter.
    

Intervention name(s): pegfilgrastim; rituximab; cyclophosphamide; doxorubicin hydrochloride; prednisone; vincristine sulfate; pharmacological study; radiation therapy
Intervention type(s): Biological; Biological; Drug; Drug; Drug; Drug; Other; 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 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 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; noncontiguous stage II adult Burkitt lymphoma; stage I adult Burkitt lymphoma; stage III adult Burkitt lymphoma; stage IV adult Burkitt lymphoma; contiguous stage II adult diffuse mixed cell lymphoma; noncontiguous stage II adult diffuse mixed cell lymphoma; stage I adult diffuse mixed cell lymphoma; stage III adult diffuse mixed cell lymphoma; stage IV adult diffuse mixed cell lymphoma; contiguous stage II adult diffuse small cleaved cell lymphoma; noncontiguous stage II adult diffuse small cleaved cell lymphoma; stage I adult diffuse small cleaved cell lymphoma; stage III adult diffuse small cleaved cell lymphoma; stage IV adult diffuse small cleaved cell lymphoma; contiguous stage II grade 1 follicular lymphoma; contiguous stage II grade 2 follicular lymphoma; contiguous stage II grade 3 follicular lymphoma; noncontiguous stage II grade 1 follicular lymphoma; noncontiguous stage II grade 2 follicular lymphoma; noncontiguous stage II grade 3 follicular lymphoma; stage I grade 1 follicular lymphoma; stage I grade 2 follicular lymphoma; stage I grade 3 follicular lymphoma; stage III grade 1 follicular lymphoma; stage III grade 2 follicular lymphoma; stage III grade 3 follicular lymphoma; stage IV grade 1 follicular lymphoma; stage IV grade 2 follicular lymphoma; stage IV grade 3 follicular lymphoma