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Phase 1 Study of Lumiliximab with Detailed Pharmacokinetic and Pharmacodynamic Measurements in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia

Authors' Affiliations: ¹ The Ohio State University Comprehensive Cancer Center, Columbus, Ohio; ² The University of Texas, M. D. Anderson Cancer Center, Houston, Texas; ³ Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland; ⁴ Moores Cancer Center of the University of California, San Diego, La Jolla, California; ⁵ Memorial Sloan-Kettering Cancer Center, New York, New York; ⁶ Long Island Jewish Medical Center, New Hyde Park, New York; and ⁷ Biogen Idec, Inc., San Diego, California

Requests for reprints: John C. Byrd, B302 Starling Loving Hall, The Ohio State University, 320 West 10th Avenue, Columbus, OH 43210. Phone: 614-293-7509; Fax: 614-293-7526; E-mail: John.Byrd{at}osumc.edu.

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/m² weekly for 4 weeks; 500 mg/m² weekly for 4 weeks [500(A)]; 500 mg/m² thrice during week 1 then 500 mg/m² weekly for the next 3 weeks [500(B)]; or 500 mg/m² 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 IgG₁ monoclonal antibodies with accumulation at doses 250 mg/m² 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/m² and was maintained for 1 week following completion of therapy at 375 mg/m².

Conclusions: Treatment with lumiliximab seemed to be well tolerated and to have clinical activity in patients with relapsed or refractory CLL.

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