Phase 1 study of lumiliximab with detailed pharmacokinetic and pharmacodynamic measurements in patients with relapsed or refractory chronic lymphocytic leukemia

Purpose: Therapeutic antibodies have improved the outcome for patients with chronic lymphocytic leukemia (CLL). We conducted a phase 1, dose escalation and schedule optimization study of the primatized anti-CD23 antibody, lumiliximab, in patients with previously treated and refractory CLL. Experimental Design: Forty-six patients were assigned sequentially to cohorts 1 through 6 and received lumiliximab at 125, 250, or 375mg/m (2) weekly for 4 weeks; 500 mg/m (2) weekly for 4 weeks [500(A)]; 500 mg/m 2 thrice during week 1 then 500 mg/m 2 weekly for the next 3 weeks [500(B)]; or 500 mg/m 2 thrice a week for 4 weeks (500 (C)], respectively. Results:The median age was 62 years (range, 47-80), and the median number of prior regimens was four (range, 1-13). No partial or complete responses were observed. Toxicity was limited and unrelated to dose. The pharmacokinetics of lumiliximab was similar to other IgG(1) monoclonal antibodies with accumulation at doses >= 250 mg/m 2 and a median terminal half-life of 7 days. Pharmacodynamic studies showed dose-dependent increases in soluble CD23, but no downregulation of CD23 antigen. Saturation of CD23 receptors occurred at 250 mg/m(2) and was maintained for >= 1 week following completion of therapy at >= 375 mg/m (2) Conclusions: Treatment with lumiliximab seemed to be well tolerated and to have clinical activity in patients with relapsed or refractory CLL.