Chemoimmuno-Therapy with Fludarabine, Cyclophosphamide and Alemtuzumab in Patients with Relapsed/Refractory CLL: Interim Analysis of the CLL2L Trial of the German CLL Study Group

Abstract

Introduction: 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 55 patients of a planned sample size of 61 patients were included in this phase-II study so far, of which 24 patients are evaluable for response and safety analysis. Median age is 63 (range 47–78) years with a medium number of 1 prior regimen; 19/24 patients completed at least four cycles with a median number of 5 cycles. Pretreatment consisted of fludarabine (8/24), fludarabine and cyclophosphamide (13/24) or rituximab combinations (3/24). Thrombocytopenia and neutropenia were the most serious side effects and detailed data will be presented. 3 CMV-reactivations, 1 Herpes-zoster-reactivation and 12 fever of unknown origin have been reported. The overall response rate was 83% with 9 CR(6 CRu) (38%), 9 PR (46%), 3 SD and 1 PD, response was independent of FISH status. A correlation of response with prior treatment was observed, with 100% ORR for fludarabine pre-treatment versus only 77% for those patients pretreated with fludarabine and cyclophosphamide. Updated data of 30 patients and MRD data will be presented. Conclusions: The concomitant application of fludarabine, cyclophosphamide and alemtuzumab appears as a safe and effective approach for patients with relapsed CLL.

State-of-the-art treatment of chronic lymphocytic leukemia

“…The combination of FC plus alemtuzumab (FCA) has been studied by the GCLLSG. 42 An interim analysis with 24 patients showed an OR rate of 83% with 9 CRs (6 CRu) (38%) and 9 PRs (46%). One herpes zoster and 3 cytomegalovirus reactivations were observed.…”