title: A phase I/II study of ofatumumab (GSK1841157) in Japanese and Korean patients with relapsed or refractory B-cell chronic lymphocytic leukemia.
abstract: The tolerability, efficacy, safety and pharmacokinetic profile of a human anti-CD20 monoclonal antibody, ofatumumab, was evaluated in this phase I/II study in patients with relapsed or refractory B-cell chronic lymphocytic leukemia (B-CLL). This study consisted of two parts. Tolerability was assessed in phase I (Part A), while the overall response rate (ORR) was assessed in phase II (comprising Parts A and B). Three patients were enrolled in Part A, and another seven patients were enrolled in Part B. Ofatumumab 300 mg was given at the first infusion, followed by seven weekly and four monthly infusions of 2000 mg. No patients experienced dose-limiting toxicity, and tolerability was confirmed. The ORR was 70 %. The most commonly reported adverse events (AEs) were leukopenia, neutropenia, and lymphopenia. No patients discontinued the study due to AEs. Plasma concentrations of ofatumumab prior to the next weekly dose increased steadily over the 8 weeks and did not reach steady state; with monthly dosing, pre-dose ofatumumab concentrations decreased. Inter-patient variability of pharmacokinetic parameters was larger after the first dose than after the later dose. In conclusion, this phase I/II study suggests that ofatumumab provides favorable safety and efficacy in Japanese/Korean patients with relapsed or refractory B-CLL.
authors.affiliation: Department of Hematology and Oncology, Tokai University School of Medicine, Shimokasuya 143, Isehara, Kanagawa 259-1193, Japan. yoshioga@is.icc.u-tokai.ac.jp
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Michinori
authors.initials: M
authors.lastname: Ogura
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Suzuki
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ando
authors.forename: Toshiki
authors.initials: T
authors.lastname: Uchida
authors.forename: Yukari
authors.initials: Y
authors.lastname: Shirasugi
authors.forename: Kensei
authors.initials: K
authors.lastname: Tobinai
authors.forename: Je Hwan
authors.initials: JH
authors.lastname: Lee
authors.forename: Masazumi
authors.initials: M
authors.lastname: Kase
authors.forename: Koichi
authors.initials: K
authors.lastname: Katsura
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Hotta
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D061067:Antibodies, Monoclonal, Humanized; D044466:Asian People; D005260:Female; D006801:Humans; D007564:Japan; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000188:drug therapy; D008231:Lymphopenia / Q000097:blood / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000097:blood / Q000139:chemically induced; D056910:Republic of Korea
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C527517:ofatumumab