Preliminary Safety and Efficacy Report of a Randomized Trial of Alemtuzumab vs Chlorambucil as Front-Line Therapy in 297 Patients with Progressive B-Cell Chronic Lymphocytic Leukemia.

CAM307, a Phase III, open-label, international, randomized trial comparing the efficacy and safety of alemtuzumab (CAMPATH®, MABCAMPATH®) with chlorambucil in B-CLL. Untreated Rai stage I-IV B-CLL patients with evidence of progressive disease were randomized 1:1 to intravenous alemtuzumab 30 mg three times a week for a maximum of 12 weeks or oral chlorambucil 40 mg/m² once every 28 days, up to a maximum of 12 cycles. Patients with autoimmune thrombocytopenia, prior bone marrow transplant, active infection, positive CMV by quantitative PCR assay, secondary malignancy or CNS involvement were excluded. All alemtuzumab patients received prophylaxis with cotrimoxazole (trimethoprim/ sulfamethoxazole DS) and famciclovir during treatment and after completion of therapy until CD4+ counts were ≥200 cells/μL. The primary endpoint for the trial is progression free survival; secondary endpoints include safety, overall survival and response rate. Patient recruitment has been completed, and demographic data are available for 297 patients (213 males, 84 females; median age 60 years; 67% Rai I/II; 33% Rai III/IV). AEs occurring in >10% of alemtuzumab patients included pyrexia, rigors, dermatitis, urticaria, headache, hypertension, hypotension (“infusion reactions”), CMV antigen reactivation, nausea and neutropenia. In chlorambucil patients, AEs occurring in >10% of patients included nausea and vomiting. A total of 7 deaths have been reported, 2 in the alemtuzumab arm and 5 in the chlorambucil arm. Two deaths in the chlorambucil arm were related to study drug. Symptomatic CMV reactivations have been tracked by investigator reports. Preliminary analysis indicates that 22 of 149 (15%) patients treated with alemtuzumab developed symptomatic CMV reactivation. In 14 of 22 (64%) cases, mild to moderate fever was the only clinical symptom. All symptomatic CMV reactivations resolved promptly with ganciclovir and most patients were able to complete alemtuzumab therapy per protocol. No symptomatic CMV reactivations have been reported in the chlorambucil arm. No deaths due to CMV have been reported. Preliminary efficacy results on approximately 100 patients that have completed 12 months of follow-up following start of treatment and were reviewed by an independent committee will be presented at the meeting. This randomized Phase III trial demonstrates that alemtuzumab as first line therapy has an acceptable toxicity profile compared to chlorambucil. Therefore, this trial will address whether treatment with alemtuzumab as front line therapy results in greater disease reduction than conventional treatment in B-CLL and whether this strategy confers a survival advantage compared to standard approaches.