Bortezomib, Combination Chemotherapy, and Rituximab as First-Line Therapy in Treating Patients With Stage III or Stage IV Follicular Non-Hodgkin's Lymphoma
Condition: Lymphoma
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, Follicular
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes
      needed for cell growth. Drugs used in chemotherapy, such as cyclophosphamide, 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. Monoclonal antibodies, such as rituximab, can
      block cancer growth in different ways. Some block the ability of cancer cells to grow and
      spread. Others find cancer cells and help kill them or carry cancer-killing substances to
      them. Giving bortezomib together with combination chemotherapy and rituximab may kill more
      cancer cells.

      PURPOSE: This phase II trial is studying the side effects and how well giving bortezomib
      together with combination chemotherapy and rituximab works when given as first-line therapy
      in treating patients with stage III or stage IV follicular non-Hodgkin's lymphoma.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Assess the efficacy of systemic first-line treatment comprising bortezomib,
           cyclophosphamide, vincristine, prednisone, and rituximab, in terms of complete response
           rate, in patients with stage III or IV follicular non-Hodgkin's lymphoma.

        -  Assess the incidence of severe neurotoxicity (defined as grade 3 or 4 neuropathy or
           neuropathic pain during the first 4 courses of treatment) in patients treated with this
           regimen.

      Secondary

        -  Assess the overall response rate and response duration in patients treated with this
           regimen.

        -  Determine progression-free and overall survival of patients treated with this regimen.

        -  Evaluate the tolerability and characterize the toxicity profile of this regimen in these
           patients.

        -  Assess quality of life, with particular focus on neurotoxicity-related changes, of
           patients treated with this regimen.

      OUTLINE: This is a multicenter, nonrandomized, open-label study.

      Patient receive cyclophosphamide IV over 15-45 minutes, vincristine IV over 3-5 seconds and
      rituximab IV over 1½-6 hours on day 1, oral prednisone daily on days 1-5, and bortezomib IV
      over 3-5 seconds on days 1 and 8. Treatment repeats every 3 weeks for up to 8 courses in the
      absence of disease progression or unacceptable toxicity.

      Quality of life is assessed at baseline, at the end of each course of treatment, and on day
      42 at the post treatment visit.

      After completion of study treatment, patients are followed at 3 and 6 weeks and then every
      3-6 months thereafter.

      PROJECTED ACCRUAL: A total of 90 patients will be accrued for this study.
    

Intervention name(s): rituximab; bortezomib; cyclophosphamide; prednisone; vincristine sulfate
Intervention type(s): Biological; Drug; Drug; Drug; Drug
Intervention description(s): 375mg/m2 day 1; 1.3mg/m2 days 1 & 8; 750mg/m2 day 1; 40mg/m2 days 1-5; 1.4mg/m2 day 1 (dose capped at 2mg)
Intervention MeSH terms: Prednisone; Cyclophosphamide; Rituximab; Vincristine; Bortezomib
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: 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