A phase I/II dose escalation study of apolizumab (Hu1D10) using a stepped-up dosing schedule in patients with chronic lymphocytic leukemia and acute leukemia.
Apolizumab (Hu1D10), a humanized monoclonal anti- Human leukocyte antigen -DR beta-chain antibody, mediates apoptosis of chronic lymphocytic leukemia (CLL) cells in vitro. We conducted a phase I/II dose-escalation study of thrice-weekly apolizumab (1.5, 3.0, 5.0 mg/kg/dose) for 4 weeks in relapsed CLL. Two of six patients at 5.0 mg/kg/dose developed treatment-related dose-limiting toxicity (aseptic meningitis, hemolytic uremia). Other toxicities included infusion toxicity, urticaria, and headache. Eleven patients were enrolled in a phase I/II expansion to evaluate the maximum tolerated dose (MTD) of 3.0 mg/kg/dose. In total, 23 patients were enrolled (22 CLL, 1 ALL). Nineteen patients with CLL were treated at or above the MTD. One partial response was observed, and three patients had stable disease exceeding 6 months. Pharmacokinetic analysis demonstrated a dose-dependent C(max) increase and serum antibody accumulation after week 1 of therapy. Given the toxicity and lack of efficacy in this and other trials in lymphoma and solid tumors, further development of apolizumab was discontinued.
Division of Hematology and Oncology, The Ohio State University, Columbus, OH 43210, USA.
Thomas S
TS
Lin
Wendy
W
Stock
Huiping
H
Xu
Mitch A
MA
Phelps
Margaret S
MS
Lucas
Sara K
SK
Guster
Bruce R
BR
Briggs
Carolyn
C
Cheney
Pierluigi
P
Porcu
Ian W
IW
Flinn
Michael R
MR
Grever
James T
JT
Dalton
John C
JC
Byrd
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005334:Fever / Q000139:chemically induced; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000139:chemically induced; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000378:metabolism; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D006684:HLA-DR Antigens; C448699:apolizumab