A Two-Arm, Multi-center Trial of Revlimid® and Rituximab, for First-Line Treatment in Patients With B-cell Chronic Lymphocytic Leukemia (CLL)
The CLL Research Consortium (CRC) is conducting a two-arm, multi-center phase II trial of
Revlimid® and rituximab for the first-line treatment of patients with CLL.
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 relapsed CLL in two
early clinical trials. However, the mechanism(s) whereby Revlimid® is active in CLL is
unknown. Rituximab (Rituxan®) is a protein that binds to CD20 expressed on normal and
leukemia B cells. Rituximab is FDA approved for the treatment of lymphoma and is used
commonly for the treatment of CLL. The purposes of this study are to evaluate the safety
and activity of the combination of Revlimid® and rituximab in CLL, elucidate the mechanism
of Revlimid® in CLL, and to assess whether prognostic factors might predict those patients
likely to benefit from this therapy in the future.
As older patients are commonly under-represented in CLL clinical trials and are less
tolerable of frontline therapy that utilizes combinations of fludarabine and
cyclophosphamide the trial has two arms; one to specifically assess for the tolerability of
the regimen in older subjects.
The primary objective of this study is to determine the response rate of the combination of
Revlimid® and Rituximab in previously untreated CLL patients in two arms- those aged 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, and the significance of
the tumor flare reaction.
All patients will have baseline assessment of known CLL prognostic factors including:
immunoglobulin variable heavy chain (IgVH) gene mutational status, interphase cytogenetics,
intracellular ZAP-70 expression, and CD38 expression 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. Extensive biologic corollary studies are designed to evaluate the
mechanism of Revlimid® in CLL, the impact of Revlimid® on the CLL microenvironment, and
Revlimid®'s impact on and rituximab mediated cytotoxicity.
All patients will receive the same treatment. Revlimid® will be started at a low dose and
slowly escalated based on patient tolerability. Rituximab will be administered following 21
days of Revlimid® monotherapy. Patients will continue treatment for up to 7 cycles unless
there is toxicity or progressive disease. There are three planned response assessments for
the subjects: a single agent Revlimid® response assessment prior to the addition of
rituximab, after 3 cycles of treatment, and following all the therapy.
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Efficacy to be assessed by clinical response rate following 3 cycles of treatment and the NCI-CLL working group response rate assessed after completion of all treatment.
clinical response assessment after 3 cycles of therapy and 3 months following completion of all therapy for NCI-CLL working group response assessment
Thomas J Kipps, M.D., Ph.D
Director of the CLL Research Consortium and University of California San Diego
United States: Food and Drug Administration
|Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University||Columbus, Ohio 43210-1240|
|Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute||Boston, Massachusetts 02115|
|Long Island Jewish Medical Center||New Hyde Park, New York 11040|
|M. D. Anderson Cancer Center at University of Texas||Houston, Texas 77030-4009|
|University of California San Diego||La Jolla, California 92093|