Phase 1/2 study of lumiliximab combined with fludarabine, cyclophosphamide, and rituximab in patients with relapsed or refractory chronic lymphocytic leukemia.

Preclinical data demonstrate enhanced antitumor effect when lumiliximab, an anti-CD23 monoclonal antibody, is combined with fludarabine or rituximab. Clinical data from a phase 1 trial with lumiliximab demonstrated an acceptable toxicity profile in patients with relapsed or refractory chronic lymphocytic leukemia (CLL). We therefore pursued a phase 1/2 dose-escalation study of lumiliximab added to fludarabine, cyclophosphamide, and rituximab (FCR) in previously treated CLL patients. Thirty-one patients received either 375 mg/m(2) (n = 3) or 500 mg/m(2) (n = 28) of lumiliximab in combination with FCR for 6 cycles. The toxicity profile was similar to that previously reported for FCR in treatment of relapsed CLL. The overall response rate was 65%, with 52% of patients achieving a complete response (CR), which compares favorably with the CR rate previously reported for the FCR regimen alone in relapsed CLL. The estimated median progression-free survival for all responders was 28.7 months. The addition of lumiliximab to FCR therapy is feasible, achieves a high CR rate, and does not appear to enhance toxicity in previously treated patients with CLL. A randomized trial comparing lumiliximab plus FCR with FCR alone is underway to define the benefit of this combination in relapsed CLL. This trial was registered at clinicaltrials.gov as NCT00103558.

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 375 mg/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 > or =250 mg/m(2) and a median terminal half-life of 7 days. Pharmacodynamic studies showed dose-dependent increases in soluble CD23, but no down-regulation of CD23 antigen. Saturation of CD23 receptors occurred at 250 mg/m(2) and was maintained for > or =1 week following completion of therapy at > or =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.