Phase II Study of Bendamustine and Rituximab Induction Chemoimmunotherapy Followed by Maintenance Rituximab (Rituxan®) and Lenalidomide (Revlimid®) in Relapsed and Refractory Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL)
CLL/SLL is an incurable disease with conventional chemotherapy, and there are limited treatment options available for patients who have become refractory to fludarabine- and alkylating-agent based regimens. Bendamustine is a recently FDA-approved agent with significant activity in CLL/SLL, including significant activity in the setting of fludarabine-refractory disease. However, durations of remission following bendamustine/rituximab combination therapy tend to be short in patients with heavily pre-treated disease or who have already received rituximab.
The incorporation of a maintenance therapy to overcome the shorter remission durations in this population is a reasonable and feasible option. In considering potential options for treatment of CLL/SLL as a maintenance strategy following induction chemotherapy, lenalidomide and rituximab are appealing options based on their convenient dosing schedules and recent evidence of acceptable toxicity and promising efficacy in combination therapy.
Chronic Lymphocytic Leukemia (CLL)
Small Lymphocytic Lymphoma (SLL)
Drug: Bendamustine and Rituximab Induction followed by Rituximab and Lenalidomide Maintenance
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||HO11415: Phase II Study of Bendamustine and Rituximab Induction Chemoimmunotherapy Followed by Maintenance Rituximab (Rituxan®) and Lenalidomide (Revlimid®) in Relapsed and Refractory Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL)|
- Progression Free Survival (PFS) [ Time Frame: Up to 30 months ] [ Designated as safety issue: No ]• The primary objective is progression-free survival for patients entering the maintenance therapy phase with rituximab and lenalidomide after induction therapy with bendamustine and rituximab. Progression is defined as radiographic or clinical progression as defined by the specified standard response criteria for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)or initiation of a new anti-neoplastic therapy in the absence of progression. Subjects with clinical evidence of progression prior to a planned disease assessment will be evaluated at the time of clinically suspected progression.
- Objective Response Rates [ Time Frame: Up to 30 months ] [ Designated as safety issue: No ]
- 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 Criteria for response in lymphoma.38 Response and progression in cases of CLL will be evaluated in this study using the Revised International Working Group CLL 2008 Criteria for Response in CLL (IWGCLL)
- 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.
- Overall survival [ Time Frame: Up to 54 months ] [ Designated as safety issue: No ]o Overall survival will be determined from the date of enrollment until death from any cause.
|Study Start Date:||November 2013|
|Study Completion Date:||August 2014|
|Primary Completion Date:||August 2014 (Final data collection date for primary outcome measure)|
Experimental: Bendamustine + Rituximab-->Rituximab and Lenalidomide
|Drug: Bendamustine and Rituximab Induction followed by Rituximab and Lenalidomide Maintenance|
Please refer to this study by its ClinicalTrials.gov identifier: NCT01754870
|United States, Wisconsin|
|University of Wisconsin Carbone Cancer Center|
|Madison, Wisconsin, United States, 53792|
|Principal Investigator:||Julie Chang, MD||University of Wisconsin, Madison|