Trial Information

Lenalidomide Following Rituximab and Fludarabine in Untreated Chronic Lymphocytic Leukemia

This is a single institution Phase II study where all enrolled patients with untreated CLL
will receive fludarabine and rituximab (FR) combination therapy. Subjects who demonstrate
Stable disease or Progressive disease after completing 3 cycles of FR will receive
lenalidomide monotherapy for a maximum of 6 cycles. Subjects who achieve >/= PR after
receiving 3 cycles of FR will receive 3 additional cycles of FR (maximum of 6 cycles). Upon
completion of FR treatment subjects will receive lenalidomide monotherapy for a maximum of 6
cycles.

Response assessment will be performed for Module A (FR): after every cycle, but would
include imaging after cycle 3 if clinically indicated. Response assessment will be
performed for Module B (Lenalidomide monotherapy): Before starting Lenalidomide therapy,
after every cycle and on completion of therapy. Imaging for Module B would be obtained
before starting lenalidomide therapy, and on completion of therapy. Bone marrow biopsies
will be performed prior to starting therapy in Module A (FR), prior to starting Module B
(Lenalidomide), and on completion of Module B. Bone marrow biopsies can be obtained once
during Lenalidomide therapy at the discretion of the investigator. Minimum residual disease
assessment of bone marrow specimens should include immunohistochemistries and flow
cytometry. Additional studies on bone marrow specimens will be sent for flow cytometric
analysis (standard or four color flow), ZAP-70 immunohistochemical stains and FISH analysis
(13q deletion, trisomy 12, 11q deletion, and 17p) will be performed at the time intervals
described above.

Response will be assessed according to the Cheson Criteria.

Blood specimens for optional correlative studies will be drawn on Day 0 prior to FR, prior
to starting lenalidomide, 90 days after initiation of lenalidomide, and 7 days after the
last dose of lenalidomide.