A Two-Arm, Multi-center Trial of Revlimid® and Rituximab, for the Treatment of Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)
The Chronic Lymphocytic Leukemia (CLL) Research Consortium (CRC) is conducting a two-arm,
multicenter phase II trial of Revlimid® and rituximab for Relapsed or Refractory Chronic
Lymphocytic Leukemia (CLL) for patients under the age of 65 and patients 65 years and older.
Revlimid® (lenalidomide) a derivative of thalidomide with immune-modulating properties.
Revlimid® is FDA approved for treatment of relapsed multiple myeloma and 5q- myelodysplastic
syndrome. Revlimid® has promising clinical activity, in both previously treated and
treatment naive CLL in early clinical trials. However, the mechanism(s) whereby Revlimid® is
active in CLL is unknown. Rituximab (Rituxan®) is a monoclonal antibody that binds to CD20
expressed on normal and leukemia B cells. Rituximab is approved for the treatment of CLL.
In preclinical models of lymphoma Revlimid improved the activity of Rituximab. In clinical
studies of relapsed and/or refractory CLL the combination Revlimid and Rituximab was
associated with better therapeutic effects compared with what was historically observed with
either agent alone.
The purpose of this study is to evaluate the safety and activity of the combination of
Revlimid® and rituximab in relapsed or refractory CLL, elucidate the mechanism of action of
Revlimid® in CLL, and to assess whether prognostic factors might predict those patients
likely to benefit from this therapy in the future.
The primary objective of this study is to determine the overall response rate (ORR) of the
combination of Revlimid® and rituximab in previously treated CLL patients for those age 65
years and above and those younger than 65.
Secondary objectives will evaluate the safety of the combination of Revlimid® and Rituximab,
response duration, improvement in hematologic parameters, activity of the combination in
high-risk CLL subsets, the significance of the tumor flare reaction and to compare the
activity of this regimen when administered to previously treated patients to our protocol in
the front line setting and to compare these outcomes for both arms of the study.
All patients will receive treatment with Revlimid® starting at a low dose that will be
slowly dose escalated based on individual patient tolerability. The combination of
Revlimid and Rituximab will be administered for a maximum of 7 cycles. Patients with
residual leukemia following seven cycles of treatment with the combination may elect to
continue on protocol for an additional 6 cycles of single agent Revlimid® consolidation.
All patients will have baseline assessment of known CLL prognostic factors through the CRC
tissue core. These known prognostic features in CLL together with novel prognostic factors
will be evaluated for the ability to predict response to treatment with Revlimid® and the
combination of Revlimid® and Rituximab.
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
iwCLL working group response rate assessed after completion of 7 cycles of treatment.
Thomas J Kipps, MD, PhD
Director of the CLL Research Consortium and University of California San Diego
United States: Food and Drug Administration
|Long Island Jewish Medical Center||New Hyde Park, New York 11040|
|Ohio State University||Columbus, Ohio 43210|
|University of California, San Diego||La Jolla, California 92037-1709|
|Dana Farber/Harvard Cancer Center at Dana farber Cancer Institute||Boston, Massachusetts 02115|