John C. Byrd, MD
Study Title: Multi-Center Trial of Revlimid ® and Rituximab for First-Line Treatment of Chronic Lymphocytic Leukemia (CLL)
Coordinator: The CLL Research Consortium is coordinating this study with support from the National Cancer Institute and Celgene.
ClinicalTrials.gov Identifier: NCT00628238
Participating Centers: This is a national, multicenter study being conducted at clinical sites within the CLL Research Consortium.
Accrual Goal: 70 patients
Study Design: This is a phase II study with two different cohorts (age less than 65 and 65 and older) of patients with symptomatic, previously untreated CLL. Lenalidomide (Revlimid®) is administered during the first month of therapy as a single agent using a dose escalation scheme designed to diminish the risk of tumor flare. Beginning with cycle 2, rituximab is added to lenalidomide with this combination therapy continuing for a maximum of 7 cycles. Incorporated into the protocol are detailed correlative studies aimed at assessing independent effects of lenalidomide on tumor cells and immune effector cells during cycle 1, pharmacokinetics and minimal residual disease.
Rationale: Lenalidomide has shown clinical activity in both previously untreated and symptomatic CLL. Reported mechanisms of action include immune modulation, interference with microenvironmental signals, anti-angiogenesis, and, in some tumor types, direct induction of apoptosis. Lenalidomide also potentiates antibody-mediated cellular cytotoxicity (ADCC). The designers of this study took advantage of this property by combining lenalidomide with the anti-CD20 chimeric antibody rituximab that, in addition to providing the antibody component of the ADCC process, has independent therapeutic activity in previously untreated CLL.
Comment: This study is designed to characterize a novel non-chemotherapy-based approach to treatment of CLL by combining two independently active biologic therapies that have synergistic potential. Given the robust number of new, highly active, targeted therapeutics (e.g., CAL-101, PCI32765) designed to treat CLL, studies such as this that examine the efficacy of these agents in combination with rituximab offer the potential of changing the approach to management of CLL to one not requiring cytotoxic, myelosuppressive chemotherapy.
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