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

• Published in: Leukemia & lymphoma Vol. 50; no. 12; pp. 1958 - 1963
• Main Authors: Lin, Thomas S., Stock, Wendy, Xu, Huiping, Phelps, Mitch A., Lucas, Margaret S., Guster, Sara K., Briggs, Bruce R., Cheney, Carolyn, Porcu, Pierluigi, Flinn, Ian W., Grever, Michael R., Dalton, James T., Byrd, John C.
• Format: Journal Article
• Language: English
• Published: United States Informa UK Ltd 01.12.2009; Taylor & Francis
• Subjects: Adult; Aged; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - pharmacokinetics; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Antibody-based immunotherapy; Area Under Curve; Dose-Response Relationship, Drug; Drug Administration Schedule; Fatigue - chemically induced; Female; Fever - chemically induced; HLA-DR Antigens - immunology; Humans; immunotherapeutic approaches; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy; Leukemia, Lymphocytic, Chronic, B-Cell - metabolism; lymphoid leukemia; Male; Metabolic Clearance Rate; Middle Aged; Myocardial Ischemia - chemically induced; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma - metabolism; Treatment Outcome
• ISSN: 1042-8194; 1029-2403
• DOI: 10.3109/10428190903186486

Apolizumab (Hu1D10), a humanized monoclonal anti- Human leukocyte antigen -DR β-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 Cmax 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.