Conditions: Chronic Lymphocytic Leukemia
Keywords: Chronic Lymphocytic Leukemia untreated minimally treated fludarabine rituximab lenalidomide
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 64
Healthy volunteers: no

Brief summary:
This phase I/II trial will combine fludarabine, rituximab, and lenalidomide in untreated or minimally treated (Phase I only) CLL patients, employing fixed doses of fludarabine and rituximab, using a schedule similar to that examined by investigators at MD Anderson (J Clin Oncol 23(18):4079-88, 2005). Given that the optimal dose and schedule is not currently known, this trial will perform a phase I component followed by a phase II examination to further explore this regimen's activity.

Detailed description:
While progress has been made in treating CLL patients over the last decade, a cure remains elusive for many patients treated with standard therapies. The combination of fludarabine, a purine analog, and rituximab, a monoclonal antibody, is an effective and frequently used therapy for CLL. However, this drug combination is associated with increased toxicity. Lenalidomide has been shown to be less toxic and has been used to treat hematologic malignancies including CLL. We propose this Phase I/Phase II study to examine the combination of lenalidomide with a rituximab/fludarabine backbone.

Arms:
arm 1: Phase I Non-stratified, dose-escalation: \>=3 patients per dose level. Safety and tolerability will be evaluated every 2 weeks during the active treatment. Doses of lenalidomide will be escalated, while the fludarabine and rituximab doses remain fixed.

Phase II The Phase II regimen will be chosen following a review of the Phase I data. Following selection of the Phase II schedule, 40 treatment naive patients will be enrolled and treated with the Phase II regimen every 28 days for up to 6 courses. For those patients achieving a CR after 3 cycles, one additional cycle of treatment will be administered beyond CR confirmation.

Interventions: intervention 1: lenalidomide intervention 2: Rituximab intervention 3: Fludarabine
Intervention descriptions: intervention 1: 2.5 mg orally (PO) daily, Days 8-28, Cycle 1; 5.0 mg PO daily, Days 8-28 Cycles 2-6 intervention 2: 375 mg/m2 Cycle 1 (split over Day 1 \& Day 2); 500 mg/m2 Day 1 of Cycles 2-6 intervention 3: 25 mg/m2 on Days 1, 2, and 3

Protocol document: