莫塞妥昔单抗治疗复发的经典型霍奇金淋巴瘤：一项开放标签、单臂、2 期临床试验。
Mocetinostat for relapsed classical Hodgkin's lymphoma: an open-label, single-arm, phase 2 trial.
机构信息
Department of Lymphoma and Myeloma, The University of Texas, M D Anderson Cancer Center, Houston, TX 77030, USA.
出版信息
Lancet Oncol. 2011 Dec;12(13):1222-8. doi: 10.1016/S1470-2045(11)70265-0. Epub 2011 Oct 25.
BACKGROUND
The prognosis of patients with relapsed Hodgkin's lymphoma, especially those who relapse after stem-cell transplantation, is poor, and the development of new agents for this patient population is an unmet medical need. We tested the safety and efficacy of mocetinostat, an oral isotype-selective histone deacetylase inhibitor, in patients with relapsed classical Hodgkin's lymphoma.
METHODS
Patients with relapsed or refractory classical Hodgkin's lymphoma aged 18 years or older were treated with mocetinostat administered orally three times per week, in 28-day cycles. Two doses were assessed (85 mg and 110 mg). Patients were treated until disease progression or prohibitive toxicity. The primary outcome was disease control rate, defined as complete response, partial response, or stable disease (for at least six cycles), analysed by intention to treat. This trial has been completed and is registered with ClinicalTrials.gov, number NCT00358982.
FINDINGS
51 patients were enrolled. Initially, 23 patients were enrolled in the 110 mg cohort. Subsequently, because toxicity-related dose reductions were necessary in the 110 mg cohort, we treated 28 additional patients with a dose of 85 mg. On the basis of intent-to-treat analysis, the disease control rate was 35% (eight of 23 patients) in the 110 mg group and 25% (seven of 28) in the 85 mg group. 12 patients (24%) discontinued treatment because of adverse events, nine (32%) in the 85 mg cohort and three (13%) in the 110 mg cohort. The most frequent treatment-related grade 3 and 4 adverse events were neutropenia (four patients [17%] in the 110 mg group, three [11%] in the 85 mg group); fatigue (five patients [22%] in the 110 mg group, three [11%] in the 85 mg group); and pneumonia (four patients [17%] in the 110 mg group, two [7%] in the 85 mg group). Four patients, all in the 110 mg cohort, died during the study, of which two might have been related to treatment.
INTERPRETATION
Mocetinostat, 85 mg three times per week, has promising single-agent clinical activity with manageable toxicity in patients with relapsed classical Hodgkin's lymphoma.
FUNDING
MethylGene Inc, Montreal, Canada; Celgene Corporation, Summit, NJ, USA; Tufts Medical Center, Boston, MA, USA.
背景
复发霍奇金淋巴瘤患者，尤其是那些在干细胞移植后复发的患者，预后较差，因此需要开发新的药物来治疗这一患者群体。本研究评估了口服异源选择性组蛋白去乙酰化酶抑制剂莫塞替尼治疗复发经典型霍奇金淋巴瘤患者的安全性和疗效。
方法
纳入年龄 18 岁及以上的复发或难治性经典型霍奇金淋巴瘤患者，采用莫塞替尼每周口服 3 次，28 天为一个周期。评估了两个剂量（85mg 和 110mg）。患者接受治疗，直至疾病进展或出现无法耐受的毒性。主要终点为疾病控制率，定义为完全缓解、部分缓解或稳定疾病（至少 6 个周期），分析采用意向治疗。本试验已完成，在 ClinicalTrials.gov 注册，编号为 NCT00358982。
结果
共纳入 51 例患者。最初，23 例患者入组 110mg 队列。随后，由于 110mg 队列中需要减少与毒性相关的剂量，我们又对 28 例患者使用 85mg 剂量进行治疗。基于意向治疗分析，110mg 组的疾病控制率为 35%（23 例患者中有 8 例），85mg 组为 25%（28 例患者中有 7 例）。12 例（24%）患者因不良事件停止治疗，其中 85mg 组 9 例（32%），110mg 组 3 例（13%）。最常见的治疗相关 3 级和 4 级不良事件为中性粒细胞减少（110mg 组 4 例[17%]，85mg 组 3 例[11%]）、疲劳（110mg 组 5 例[22%]，85mg 组 3 例[11%]）和肺炎（110mg 组 4 例[17%]，85mg 组 2 例[7%]）。4 例患者（均在 110mg 组）在研究期间死亡，其中可能与治疗相关的有 2 例。
结论
每周 3 次、85mg 的莫塞替尼在复发经典型霍奇金淋巴瘤患者中具有良好的单药临床活性，且毒性可耐受。
资助
加拿大蒙特利尔美杰基因公司（MethylGene Inc）、美国新泽西州 Summit 的 Celgene 公司、美国马萨诸塞州波士顿的塔夫茨医疗中心（Tufts Medical Center）。
Zotero 插件