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 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 cyclophosphamide, prednisone, and rituximab may be an effective treatment for non-Hodgkin's lymphoma.
PURPOSE: This phase I/II trial is studying the side effects and best dose of bortezomib when given together with cyclophosphamide, prednisone, and rituximab and to see how well it works in treating patients with relapsed or refractory indolent B-cell non-Hodgkin's lymphoma.
Primary Outcome Measures:
- Maximum tolerated dose [ Designated as safety issue: Yes ]
Secondary Outcome Measures:
- Progression-free survival [ Designated as safety issue: No ]
- Duration of response (mean and median) [ Designated as safety issue: No ]
- Event-free survival [ Designated as safety issue: No ]
- Overall survival [ Designated as safety issue: No ]
- Toxicity [ Designated as safety issue: Yes ]
Estimated Enrollment: |
115 |
Study Start Date: |
December 2005 |
Estimated Primary Completion Date: |
September 2010 (Final data collection date for primary outcome measure) |
OBJECTIVES:
Primary
- Determine the maximum tolerated dose of bortezomib when given in combination with rituximab, cyclophosphamide, and prednisone (R-CP) in patients with relapsed or refractory indolent B-cell lymphoproliferative disorders or mantle cell lymphoma. (phase I)
- Determine the frequency and duration of complete and partial responses in patients treated with this regimen. (phase II)
Secondary
- Evaluate the progression-free survival, event-free survival, and overall survival of patients treated with this regimen. (phase II)
- Evaluate the toxicity profile of this regimen.
OUTLINE: This is a phase I dose-escalation study of bortezomib followed by a phase II non-randomized, multicenter study. Patients in phase II are stratified according to disease (mantle cell lymphoma vs other diagnoses).
- Phase I: Patients receive cyclophosphamide IV and rituximab IV on day 1, oral prednisone on days 2-6, and bortezomib IV on days 2 and 7. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 1 of 3 or 2 of 6 patients experience dose-limiting toxicity.
- Phase II: Patients receive cyclophosphamide, rituximab, prednisone, and bortezomib at the MTD as in phase I.
After completion of study treatment, patients are followed periodically.
PROJECTED ACCRUAL: A total of 115 patients will be accrued for this study.