Preliminary phase III efficacy and safety of alemtuzumab vs chlorambucil as front-line therapy for patients with progressive B-cell chronic lymphocytic leukemia (BCLL)

Abstract

6511 Background: Phase 3, open-label, randomized comparative trial, enrolled Rai stage I-IV BCLL patients with previously untreated, progressive disease requiring treatment. Objectives: Compare efficacy and safety of alemtuzumab (CAMPATH [(CAM]) to chlorambucil (CHLO) as front-line therapy. Methods:Patients were randomized 1:1 to CAM 30 mg IV 3x/week for a maximum of 12 weeks (wks) or CHLO 40 mg/m2 PO once every 28 days, to a maximum of 12 cycles. All CAM patients received prophylactic antibiotic (trimethoprim/sulfamethoxazole DS) and antiviral (famciclovir) treatment during therapy and until CD4+ counts were ≥200 cells/μL. The primary endpoint was progression free survival; secondary endpoints included safety, response rate and overall survival. Results: Accrual completed in July 2004 with 297 patients enrolled (213 males, 84 females; median age 60 years); CAM n=149 and CHLO n=148. Treatment arms were balanced for key prognostic factors analyzed to date. Most patients had performance status 0–1 (96%) and maximum lymph nodes <5cm (70%). Median length of treatment with CAM = 11.7 wks, CHLO = 24.4 wks. The design provided for investigator assessment and an independent review of response (IRR). Preliminary data from the IRR are presented. Response rate for CHLO was consistent with historical data. Safety data indicate 34.7% of CAM patients and 19.7% of CHLO patients experienced a serious adverse event, with 21.1% and 4.1% considered drug related, respectively. The incidence of grade 3/4 thrombocytopenia and anemia were comparable in both treatment arms. Grade 3/4 neutropenia (42.2% vs 23.1%), infections (excluding CMV) (14.3% vs 6.8%), and CMV infections (6.8% vs 0%) were more frequent in the CAM arm. One treatment related death occurred in the CHLO arm. Conclusions: Preliminary efficacy and safety data confirm therapy naïve BCLL patients treated with single agent CAM have an excellent response rate with a manageable toxicity profile. [Table: see text] [Table: see text]