Phase 3 study of oral lenalidomide as maintenance therapy for patients with B-cell chronic lymphocytic leukemia (CLL).

Abstract:

Background: Despite recent advances in chemo-immunotherapy combinations for the treatment (Tx) of CLL, most patients (pts) relapse and eventually die from the disease. Maintenance therapy has made impact in other B-cell cancers, such as myeloma; its role and the optimal agent in CLL is unknown. Recent trials of rituximab have shown promise as maintenance therapy; however, the clinical use may be limited due to the intravenous formulation. Lenalidomide (LEN) shows encouraging efficacy in CLL pts; this and its positive impact on survival outcome as maintenance Tx in myeloma pts rationalizes its investigation in CLL. Additionally, the oral formulation makes it better suited as a long-term, single-agent Tx regimen. 

Methods: This phase 3, multicenter, randomized, double-blind, placebo controlled, parallel-group study investigates the efficacy and safety of oral LEN as maintenance therapy for CLL pts who showed a partial response (PR) to second-line therapy. Primary objectives are PFS and OS. Secondary objectives include safety, tumor response, response duration and health-related quality of Life. Additionally, the occurrence of secondary primary malignancy is monitored. Eligible pts (≥18 years) have previously received a chlorambucil-, a purine analog-, an anti-CD20-antibody-, or a bendamustine-based regimen in first-and/or second-line therapy, and must have achieved ≥PR to second-line therapy. Pts with del(17p) may have previously received an alemtuzumab-containing regimen. 400 pts (260 pts currently enrolled) with ≥PR following second-line therapy will be enrolled and randomized (1:1) to either the placebo or the LEN arm. Pts will receive placebo or 2.5 mg LEN per day (QD) on days 1-28 of each 28-day cycle. Subsequent LEN dose escalation to 5 mg QD at cycle 2 and to 10 mg at cycle 6 may occur, if tolerated in the previous cycle. Prior to study commencement, pts are tested for poor prognostic indicators (del(17p), del(11q), unmutated IGVH and high B2M). Exploratory biomarkers include (ZAP-70, immune cell analysis and CD80). This study is conducted in accordance with good clinical practice and all applicable regulatory requirements. Clinical trial information: NCT00774345.

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Citation:
J Clin Oncol 32:5s, 2014 (suppl; abstr TPS7125)