Bortezomib, Rituximab, Cyclophosphamide, and Prednisone in Treating Patients With Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma
- Conditions
- LeukemiaLymphoma
- Interventions
- Registration Number
- NCT00295932
- Lead Sponsor
- Memorial Sloan Kettering Cancer Center
- Brief 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 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 randomized 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.
- Detailed Description
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 two different treatment regimes. (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 randomized, multicenter study. Patients in phase II are stratified according to disease (mantle cell lymphoma vs indolent B-cell lymphoproliferative disorder vs transformed lymphoma).
* 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 are randomized to 1 of 2 treatment arms.
* Arm I: Patients receive cyclophosphamide IV and rituximab IV on day 1, oral prednisone on days 2-6, and bortezomib IV (at the MTD determined in phase I) on days 2, 5, 9, and 12. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.
* Arm II: Patients receive cyclophosphamide IV and rituximab IV on day 1, oral prednisone on days 2-6, and bortezomib IV (at the MTD determined in phase I) on days 2 and 8. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed at 1 month, every 4 months for 2 years, and then every 6 months thereafter.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 79
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm I rituximab Patients receive cyclophosphamide IV and rituximab IV on day 1, oral prednisone on days 2-6, and bortezomib IV (at the MTD determined in phase I) on days 2, 5, 9, and 12. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Arm I bortezomib Patients receive cyclophosphamide IV and rituximab IV on day 1, oral prednisone on days 2-6, and bortezomib IV (at the MTD determined in phase I) on days 2, 5, 9, and 12. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Arm I prednisone Patients receive cyclophosphamide IV and rituximab IV on day 1, oral prednisone on days 2-6, and bortezomib IV (at the MTD determined in phase I) on days 2, 5, 9, and 12. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Arm II rituximab Patients receive cyclophosphamide IV and rituximab IV on day 1, oral prednisone on days 2-6, and bortezomib IV (at the MTD determined in phase I) on days 2 and 8. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Arm I cyclophosphamide Patients receive cyclophosphamide IV and rituximab IV on day 1, oral prednisone on days 2-6, and bortezomib IV (at the MTD determined in phase I) on days 2, 5, 9, and 12. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Arm II cyclophosphamide Patients receive cyclophosphamide IV and rituximab IV on day 1, oral prednisone on days 2-6, and bortezomib IV (at the MTD determined in phase I) on days 2 and 8. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Arm II bortezomib Patients receive cyclophosphamide IV and rituximab IV on day 1, oral prednisone on days 2-6, and bortezomib IV (at the MTD determined in phase I) on days 2 and 8. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Arm II prednisone Patients receive cyclophosphamide IV and rituximab IV on day 1, oral prednisone on days 2-6, and bortezomib IV (at the MTD determined in phase I) on days 2 and 8. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.
- Primary Outcome Measures
Name Time Method Maximum Tolerated Dose 2 years Maximum tolerated dose of Bortezomib in combination with Rituximab, Cyclophosphamide and Prednisone in Phase I participants
- Secondary Outcome Measures
Name Time Method Progression-free Survival 2 years Event-free Survival 2 years Toxicity of Participants Receiving Bortezomib, Rituximab, Cyclophosphamide, and Prednisone for Treatment of Non-Hodgkin's Lymphoma 2 years Toxicity assessed using NCI-CTC v. 3.0
Duration of Response (Mean and Median) 2 years Overall Survival 2 years
Trial Locations
- Locations (8)
Memorial Sloan-Kettering Cancer Center @ Suffolk
🇺🇸Commack, New York, United States
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
🇺🇸New Brunswick, New Jersey, United States
Memorial Sloan-Kettering at Basking Ridge
🇺🇸Basking Ridge, New Jersey, United States
Winship Cancer Institute of Emory University
🇺🇸Atlanta, Georgia, United States
Memorial Sloan-Kettering at Mercy Medical Center
🇺🇸Rockville Centre, New York, United States
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
🇺🇸New York, New York, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
Memoral Sloan Kettering Cancer Center@Phelps
🇺🇸Sleepy Hollow, New York, United States