6599 Background: Recent data reporting results of FCR therapy in previously untreated advanced CLL patients (F-25 mg/m2 d1–3 q 4wk; C-250 mg/m2 d 1–3 q 4wk; R-500 mg/m2 d1 q 4wk for 6 cycles) demonstrated complete remission (CR) of 70% and overall response (OR) of 95% (J Clin Oncol 2005;23:4079). The major toxicity was grade 3/4 neutropenia during 52% of courses. One approach to decrease neutropenia without compromising efficacy could be by reducing the doses of F and C and increasing the dose of R as high-dose R has been reported to be more efficacious in CLL. Methods: We conducted a phase II study for previously untreated advanced CLL patients treated with mFCR (F-20mg/m2 d1–3 q 4 wk; C-150 mg/m2 d1–3 q 4 wk; R-500mg/m2 d1 and d14 q 4wks; maintenance R-500 mg/m2 q 3 months until progression). A Simon two-stage design was used where 15 patients were accrued in the first stage and because of acceptable toxicity and response rate in stage I an additional 35 patients will be treated. The primary endpoint was response rate. Results: Twenty patients (13 male, 7 female), age 36–85 years (median 59) were treated with a total of 105 mFCR courses. All 20 patients were evaluable for toxicity. Grade 3/4 neutropenia occurred during 11(10.5%) courses. There were no episodes of neutropenic fever. Grade 3/4 thrombocytopenia occurred during 4 (3.8%) courses. Two patients are currently on study and not evaluable for response and among the 18 evaluable patients, the CR was 68%, PR was 32% with an OR of 100%. Eleven of the 12 CR patients had no evidence of CD5+/CD19+ coexpressing cells in their bone marrow after therapy and one had <1%; all 12 were NED by CT scan. Conclusions: Our preliminary results suggest mFCR is highly effective with considerably less grade 3/4 neutropenia than standard FCR. Complete responders had minimal residual disease in their bone marrow following mFCR. [Table: see text]