Rituximab, Lenalidomide, and Bortezomib in Mantle Cell Lymphoma
This is a Phase I/II multicenter, open-label, dose-escalation study of rituximab, bortezomib, and lenalidomide in the first-line or second-line treatment of patients with Mantle Cell Lymphoma (MCL).
Mantle Cell Lymphoma
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Study Evaluating Rituximab, Lenalidomide, and Bortezomib in the First-Line or Second-Line Treatment of Patients With Mantle Cell Lymphoma|
- Determine Maximum Tolerated Dose (MTD) [ Time Frame: 18 months ] [ Designated as safety issue: No ]Determine the maximum tolerated dose (MTD) of the combination of lenalidomide, bortezomib, and rituximab in patients with relapsed or refractory mantle cell lymphoma (MCL) who have received one prior therapy.
- Assessment of safety and tolerability based on frequency of Adverse Events (AEs) [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]Determine the safety and tolerability of the combination of lenalidomide, bortezomib, and rituximab in patients with previously untreated MCL and patients with relapsed or refractory MCL who have received one prior therapy
- To make preliminary estimates of the efficacy of the combination of lenalidomide, bortezomib, and rituximab in patients with previously untreated MCL and patients with relapsed or refractory MCL who have received one prior therapy. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
- Determine time to best response, duration of response, progression-free survival (PFS), and overall survival. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
|Study Start Date:||June 2008|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||November 2015 (Final data collection date for primary outcome measure)|
Patients in Phase I and Phase II will receive treatment with rituximab, bortezomib, and lenalidomide in 21-day cycles.
For Phase I, patients in the first cohort will receive (Dose Level 1):
For Cycle 1: rituximab 375 mg/m2 intravenously (IV) on Days 1, 8, and 15; bortezomib 1.3 mg/ m2 SC on Days 1, 4, 8, and 11; and lenalidomide 15 mg by mouth (PO) daily on Days 1-14.
For Cycles 2 - 6: rituximab 375 mg/m2 IV on Day 1; bortezomib 1.3 mg/ m2 SC on Days 1, 4, 8, and 11; and lenalidomide 15 mg PO daily on Days 1 14.
Doses will be escalated in subsequent patient cohorts as described in the protocol; doses may also be de-escalated if necessary.
Patients in Phase II will be treated with the DL-1 dose determined in Phase I. However, if patients experience no treatment-related adverse events on DL-1 after 2 cycles, then the treating physician will have the option of escalating to DL1 for subsequent cycles.
Cycle 1: Rituximab 375 mg/m2 intravenously (IV) on Days 1, 8, and 15 Cycles 2 - 6: rituximab 375 mg/m2 IV on Day 1
Other Names:Drug: Bortezomib
Bortezomib 1.3 mg/ m2 IV on Days 1, 4, 8, and 11
Other Name: VelcadeDrug: Lenalidomide
Lenalidomide 15 mg by mouth (PO) daily on Days 1-14
Other Name: Revlimid
The combination of lenalidomide with bortezomib has not been studied in patients with MCL, but feasibility and tolerability has been demonstrated in patients with multiple myeloma. Thus, almost every 2-drug combination of rituximab, lenalidomide, and bortezomib has been tested, or is being tested. We hypothesize that all three drugs are important in MCL, and therefore propose to combine all 3 agents (rituximab, bortezomib, and lenalidomide) in a schedule that is convenient to lymphoma patients.
Approximately 18 patients may be enrolled in the Phase I portion of the study. Approximately 45 patients are planned for enrollment in Phase II.
|United States, Indiana|
|RHHP/ Hope Cancer Center|
|Terre Haute, Indiana, United States, 47802|
|Providence Medical Group|
|Terre Haute, Indiana, United States, 47802|
|United States, Missouri|
|St. Louis Cancer Care|
|Chesterfield, Missouri, United States, 63017|
|United States, New Jersey|
|Hematology-Oncology Associates of Northern NJ|
|Morristown, New Jersey, United States, 07960|
|United States, Ohio|
|Oncology Hematology Care Inc.|
|Cincinnati, Ohio, United States, 45242|
|United States, Tennessee|
|Chattanooga Oncology Hematology Associates|
|Chattanooga, Tennessee, United States, 37404|
|Tennessee Oncology, PLLC|
|Nashville, Tennessee, United States, 37023|
|Study Chair:||Ian W Flinn, M.D.||SCRI Development Innovations, LLC|