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


METHODS
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.
The Ohio State University Comprehensive Cancer Center, Columbus, Ohio 43210, USA. John.Byrd@osumc.edu
John C
JC
Byrd
Susan
S
O'Brien
Ian W
IW
Flinn
Thomas J
TJ
Kipps
Mark
M
Weiss
Kanti
K
Rai
Thomas S
TS
Lin
James
J
Woodworth
Dee
D
Wynne
Jennifer
J
Reid
Arturo
A
Molina
Bryan
B
Leigh
Sarah
S
Harris
D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000378:metabolism*; D007958:Leukocyte Count; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000378:metabolism*; D017455:Receptors, IgE / Q000378:metabolism; D016879:Salvage Therapy; D015996:Survival Rate; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D017455:Receptors, IgE; C509683:lumiliximab