Phase II Study of Bendamustine and Rituximab Induction Chemoimmunotherapy Followed by Maintenance Rituximab (Rituxan®) and Lenalidomide (Revlimid®) in Previously Untreated Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL)
The investigators propose a treatment strategy where patients are treated with induction chemoimmunotherapy consisting of rituximab + bendamustine for 6 cycles, followed by initiation of maintenance rituximab and lenalidomide among patients achieving an objective response (i.e., at least stable disease with some tumor shrinkage) to induction therapy. The goal of maintenance therapy will be to capitalize on the cytoreduction following induction chemotherapy with a maintenance regimen that has also shown promising activity in CLL, in order to allow for improved PFS in this population.
Chronic Lymphocytic Leukemia (CLL)
Small Lymphocytic Lymphoma (SLL)
Drug: Bendamustine and Rituximab induction with Rituximab and Lenalidomide Maintenance
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||HO11414: Phase II Study of Bendamustine and Rituximab Induction Chemoimmunotherapy Followed by Maintenance Rituximab (Rituxan®) and Lenalidomide (Revlimid®) in Previously Untreated Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL)|
- Time to progression [ Time Frame: Up to 30 months ] [ Designated as safety issue: No ]The primary objective is progression-free survival (PFS). Tumor measurements and disease assessments will be performed at the time of screening, following cycles 3 and 6 of induction chemotherapy, every 4 cycles during the maintenance portion of treatment, and at the end of treatment (EOT). Subjects with clinical evidence of progression prior to a planned disease assessment will be evaluated at the time of clinically suspected progression. Follow-up visits for disease assessment will occur every 3 months after the EOT visit until PD, initiation of alternate anti-neoplastic therapy, decision by the subject to withdraw from the study, or death. The follow-up period will begin after the EOT visit, and all subjects will be followed for at least 2 years after completion of therapy or until death or progression and until the last patient has been followed for at least 1 year following completion of therapy.
- Objective Response Rates [ Time Frame: Up to 30 months ] [ Designated as safety issue: No ]To determine objective response rates (CR + PR). As described in the primary objective, formal disease assessments including imaging will be performed after cycles 3 and 6 of induction chemotherapy and every 4 cycles during the maintenance portion of treatment. Response and progression in cases of SLL will be evaluated using the International Working Group Criteria30 for response in lymphoma. Response and progression in cases of CLL will be evaluated in this study using the Revised IWCLL Criteria31 for response in CLL. Radiological methodologies, techniques and/or physical examination, established at baseline for the assessment and measurement of each identified lesion will be used for all subsequent assessments.
- Toxicity [ Time Frame: Up to 30 months ] [ Designated as safety issue: Yes ]• To determine toxicities observed with induction chemotherapy and maintenance therapy. Safety evaluations will be based on the incidence, intensity, and type of adverse events (AEs) and clinical laboratory results. Drug doses will be modified as required based on toxicity as assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0.
- Time to Death [ Time Frame: Up to 54 months ] [ Designated as safety issue: No ]• To determine overall survival. Overall survival will be determined from the date of enrollment until death from any cause.
|Study Start Date:||November 2013|
|Estimated Study Completion Date:||December 2017|
|Estimated Primary Completion Date:||December 2017 (Final data collection date for primary outcome measure)|
Experimental: Bendamustine + Rituximab-->Rituximab and Lenalidomide
Induction chemoimmunotherapy with bendamustine 90 mg/m2/day IV days 1 & 2 and rituximab 500 mg/m2 day 1 (375 mg/m2 cycle 1)every 28 days for 6 cycles.
Rituximab maintenance 375 mg/m2 IV on day 1 of odd-numbered 28 day cycles for a total of 12 doses. Lenalidomide maintenance administered as 5 mg/day on days 1-28 of cycles 1-24 (28-day cycles), with dose escalation up to 10 mg/day allowed.
|Drug: Bendamustine and Rituximab induction with Rituximab and Lenalidomide Maintenance|
Please refer to this study by its ClinicalTrials.gov identifier: NCT01754857
|United States, Wisconsin|
|University of Wisconsin|
|Madison, Wisconsin, United States, 53792|
|Principal Investigator:||Julie Chang, MD||University of Wisconsin, Madison|