Department of Hematology and Oncology, Tokai University School of Medicine, Shimokasuya 143, Isehara, Kanagawa 259-1193, Japan.
Int J Hematol. 2013 Aug;98(2):164-70. doi: 10.1007/s12185-013-1393-x. Epub 2013 Jul 12.
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.
这项 I/II 期研究评估了一种人源抗 CD20 单克隆抗体奥法妥木单抗（ofatumumab）在复发/难治性 B 细胞慢性淋巴细胞白血病（B-CLL）患者中的耐受性、疗效、安全性和药代动力学特征。该研究包括两部分。I 期（A 部分）评估了耐受性，II 期（包括 A 部分和 B 部分）评估了总缓解率（ORR）。A 部分入组了 3 例患者，B 部分入组了 7 例患者。首次输注时给予奥法妥木单抗 300mg，随后每周输注 7 次，每次 2000mg，每月输注 4 次。没有患者出现剂量限制性毒性，且耐受性得到了确认。ORR 为 70%。最常见的不良事件（AE）是白细胞减少、中性粒细胞减少和淋巴细胞减少。没有患者因 AE 而停止研究。在接下来的每周剂量前，奥法妥木单抗的血浆浓度在 8 周内持续稳定升高，但未达到稳态；每月给药时，奥法妥木单抗的预剂量浓度降低。在首次剂量后，药代动力学参数的个体间变异性大于后续剂量。综上所述，这项 I/II 期研究表明，奥法妥木单抗在复发/难治性 B-CLL 的日本/韩国患者中具有良好的安全性和疗效。
