Ofatumumab maintenance versus observation in relapsed chronic lymphocytic leukaemia (PROLONG): an open-label, multicentre, randomised phase 3 study
Ofatumumab maintenance versus observation in relapsed chronic lymphocytic leukaemia (PROLONG): an open-label, multicentre, randomised phase 3 study
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DOI：
10.1016/s1470-2045(15)00143-6
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发表时间：
2015-10-01
期刊：
影响因子：
51.1
通讯作者：
Geisler, Christian
中科院分区：
文献类型：
--
作者：
van Oers, Marinus H. J.;Kuliczkowski, Kazimierz;Geisler, Christian
背景 Ofatumumab 是一种人抗 CD20 单克隆抗体，已被证明作为难治性慢性淋巴细胞白血病的单一疗法有效。我们评估了奥法木单抗维持治疗与观察复发性慢性淋巴细胞白血病重新诱导治疗后缓解患者的疗效和安全性。 方法 这项开放标签、多中心、随机 3 期研究纳入了来自 24 个国家 130 个中心的 18 岁或以上的患者，这些患者在二线或三线治疗后患有完全或部分缓解的慢性淋巴细胞白血病。符合条件的患者的WHO体能状态为0-2，在过去3个月内进行过缓解评估，没有难治性疾病、需要治疗的自身免疫性溶血性贫血、需要治疗的慢性或活动性感染，并且既往未接受过维持治疗或自体或同种异体干细胞移植。使用中央计算机系统和交互式语音识别系统生成的随机列表，我们随机分配（1:1）患者接受奥法木单抗治疗（300 mg，1 周后 1000 mg，每 8 周一次，持续长达 2 年）或接受观察。随机分组根据既往治疗的数量和类型以及诱导治疗后的缓解状态进行分层（区块大小为四）。治疗分配是开放标签的。主要终点是研究者评估的意向治疗人群的无进展生存期。在三分之二的计划研究事件（疾病进展或死亡）发生后，我们报告预先指定的中期分析的结果。该试验已结束，但后续工作仍在进行中。该试验在ClinicalTrials.gov上注册，编号NCT00802737。结果2010年5月6日至2014年6月19日期间，我们入组了474名患者：238名患者被随机分配接受奥法木单抗维持治疗，236名患者接受观察。一 （
Background Ofatumumab is a human anti-CD20 monoclonal antibody that has proven efficacy as monotherapy in refractory chronic lymphocytic leukaemia. We assessed the efficacy and safety of ofatumumab maintenance treatment versus observation for patients in remission after re-induction treatment for relapsed chronic lymphocytic leukaemia.Methods This open-label, multicentre, randomised phase 3 study enrolled patients aged 18 years or older from 130 centres in 24 countries who had chronic lymphocytic leukaemia in complete or partial remission after second-line or third-line treatment. Eligible patients had a WHO performance status of 0-2, had a response assessment within the previous 3 months, did not have refractory disease, autoimmune haemolytic anaemia requiring treatment, chronic or active infection requiring treatment, and had not previously received maintenance treatment or autologous or allogeneic stem-cell transplant. Using a randomisation list generated by a central computerised system and an interactive voice recognition system, we randomly assigned (1: 1) patients to receive ofatumumab (300 mg followed by 1000 mg 1 week later and every 8 weeks for up to 2 years) or undergo observation. Randomisation was stratified by number and type of previous treatment and remission status after induction treatment (block size of four). Treatment assignment was open label. The primary endpoint was investigator-assessed progression-free survival in the intentionto-treat population. We report the results of a prespecified interim analysis after two-thirds of the planned study events (disease progression or death) had happened. This trial is closed to accrual but follow-up is ongoing. This trial is registered with ClinicalTrials.gov, number NCT00802737.Findings Between May 6, 2010, and June 19, 2014, we enrolled 474 patients: 238 patients were randomly assigned to receive ofatumumab maintenance treatment and 236 to undergo observation. One (