Trial Information

A Randomized Phase II Study of Concurrent Fludarabine + Chimeric Anti-CD20 Monoclonal Antibody IDEC-C2B8 (Rituximab) [NSC# 687451] Induction Followed By Rituximab Consolidation In Untreated Patients With B-Cell Chronic Lymphocytic Leukemia

OBJECTIVES: I. Determine the response rate and toxicity profile of concurrent and
consolidative chimeric anti-CD20 monoclonal antibody IDEC-C2B8 (rituximab) therapy compared
to consolidative rituximab therapy in patients with chronic lymphocytic leukemia treated
with fludarabine. II. Assess the complete response (CR) rate in patients receiving
concurrent therapy with rituximab and fludarabine. III. Assess the frequency of conversion
of a partial response (PR) to a CR or stable disease to either PR or CR in patients
receiving consolidative therapy with rituximab. IV. Follow the effects of rituximab and
fludarabine on the immunologic markers CD4, CD8, IgG, IgA, and IgM. V. Assess the
progression-free and overall survival of these patients.

OUTLINE: This is a randomized study. Patients are stratified according to stage (I and II vs
III and IV). Patients are assigned to 1 of 2 treatment arms. Arm I consists of fludarabine
and chimeric anti-CD20 monoclonal antibody IDEC-C2B8 (rituximab) induction, and arm II
consists of fludarabine induction. Arm I: Rituximab is administered IV over 4 hours on day
1, on day 3, and over 1 hour on day 5 of week 1. Subsequent doses are given over 1 hour on
day 1 every 4 weeks for a total of 6 courses. Fludarabine IV is administered over 10-30
minutes daily for 5 days during weeks 1, 5, 9, 13, 17, and 21 for a total of 6 courses.
Following the sixth course of fludarabine, patients undergo clinical staging and are then
observed for an additional 2 months, after which they undergo repeat clinical staging,
including bone marrow aspiration. Patients achieving a complete or partial response or
stable disease then proceed to consolidation therapy consisting of weekly intravenous
infusions of rituximab once weekly for 4 weeks. Arm II (Fludarabine Induction): Patients
receive fludarabine IV over 10-30 minutes daily for 5 days during weeks 1, 5, 9, 13, 17, and
21 for a total of 6 courses. Patients then proceed as in arm I. Patients are followed every
3 months for 1 year, and then every 6 months thereafter.

PROJECTED ACCRUAL: A maximum of 100 patients will be accrued for this study within 12
months.