A Phase I/II Dose Escalation Study of Apolizumab (Hu1D10) Using a Stepped Up Dosing Schedule in Patients with Chronic Lymphocytic Leukemia (CLL) and Acute Leukemia
| Autor: | Carolyn Cheney, Wendy Stock, Huiping Xu, Mitch A. Phelps, Bruce R. Briggs, Sara K. Guster, Thomas S. Lin, Margaret S. Lucas, John C. Byrd, Ian W. Flinn, James T. Dalton, Pierluigi Porcu, Michael R. Grever |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Adult
Male Cancer Research medicine.medical_specialty Fever Metabolic Clearance Rate Chronic lymphocytic leukemia Myocardial Ischemia Pharmacology Antibodies Monoclonal Humanized Gastroenterology Drug Administration Schedule Article Internal medicine hemic and lymphatic diseases medicine Humans Fatigue Aged Acute leukemia Dose-Response Relationship Drug business.industry Antibodies Monoclonal Hematology HLA-DR Antigens Middle Aged Precursor Cell Lymphoblastic Leukemia-Lymphoma medicine.disease Leukemia Lymphocytic Chronic B-Cell Lymphoma Apolizumab Leukemia Treatment Outcome Oncology Area Under Curve Monoclonal Toxicity Female business Lymphoid leukemia medicine.drug |
| Zdroj: | Leuk Lymphoma |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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