Treatment of patients with relapsed/refractory CLL using a combination of fludarabine, cyclophosphamide and alemtuzumab: First safety analysis of the CLL2L trial of the German CLL Study Group

Abstract

7053 Background: Purine nucleoside combination therapy has become the standard treatment approach in B-CLL. In order to enhance efficacy, various combinations with monoclonal antibodies are under investigation. As alemtuzumab has proven to be the most effective antibody in CLL treatment, we developed a multicenter phase II trial combining fludarabine, cyclophosphamide and alemtuzumab in a 4-weekly schedule. Methods: Fludarabine 25mg/m2 iv, cyclophosphamide 200mg/m2 iv and alemtuzumab 30 mg sc were given on days 1 - 3 and repeated on day 29 for up to six cycles. A 2-day escalation of alemtuzumab was administered prior to the first cycle. Minimal residual disease (MRD) was measured by 4-color flow cytometry. Antiinfective prophylaxis consisted of TMP-SMZ DS twice daily 3d/wk and valacyclovir during and at least two months after completion of treatment. CMV antigen in blood was tested in 14-days intervals. Results: A total of 39 patients of a planned sample size of 61 patients were included in this phase-II study so far, of which 20 patients are evaluable for response and safety analysis. Median age is 64 (range 48–78) years with a medium number of 1 prior regimen; 14/20 patients completed at least four cycles with a median number of 4.5cycles. Pretreatment consisted of fludarabine (8/20), fludarabine and cyclophosphamide (12/20) or rituximab combination (1/20). Thrombocytopenia and neutropenia were the most serious side effects and detailed data will be presented. 2 CMV-reactivations, 1 Herpes-zoster-reactivation and 12 fever of unknown origin have been reported. The overall response rate was 70% with 5 CR (25%), 9 PR (45%), 2 SD and 2 PD. All complete responders became MRD negative in peripheral blood or bone marrow; response was independent of FISH status. A correlation of response with prior treatment was observed, with 88% ORR for fludarabine pre-treatment versus only 65% for those patients pretreated with fludarabine and cyclophosphamide. Conclusions: The concomitant application of fludarabine, cyclophosphamide and alemtuzumab appears as a safe and effective approach for patients with relapsed CLL. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer Schering AG, Schering AG Schering AG