| Abstract: |
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. © 2007 American Association for Cancer Research. |
| Keywords: |
adult; clinical article; treatment outcome; treatment response; aged; aged, 80 and over; middle aged; survival rate; unclassified drug; fludarabine; clinical trial; constipation; drug activity; drug tolerability; fatigue; neutropenia; salvage therapy; dose response; side effect; rituximab; recurrent cancer; follow-up studies; neoplasm recurrence, local; anemia; leukopenia; nausea; thrombocytopenia; myalgia; relapse; cyclophosphamide; continuous infusion; dose-response relationship, drug; abdominal pain; coughing; drug dose escalation; dyspnea; fever; pneumonia; rash; hypoxia; hypotension; antibodies, monoclonal; rigor; drug accumulation; hemolytic anemia; granisetron; autoimmune hemolytic anemia; headache; optimal drug dose; leukocyte count; maximum tolerated dose; phase 1 clinical trial; drug half life; chronic lymphatic leukemia; gastrointestinal disease; immunoglobulin g1 antibody; alemtuzumab; parainfluenza virus infection; night sweat; skin allergy; abdominal distension; diaphoresis; receptors, ige; cd23 antigen; nose congestion; receptor occupancy; leukemia, lymphocytic, chronic; lumiliximab; monoclonal antibody cd23; refractory cancer
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