METHODS: A prospective, multicenter, single arm, phase 1b/2 study was conducted. A total of 128 patients with untreated PTCL (18-70 years of age) were enrolled between March 2016 and November 2019, and treated with up to 6 cycles with the Chi-CHOEP regimen. In the phase 1b study, 3 dose levels of chidamide were evaluated and the primary endpoint was determination of the maximum-tolerated dose and recommended phase 2 dose (RP2D). The primary endpoint of the phase 2 study was 2-year progression-free survival (PFS).
RESULTS: Fifteen patients were enrolled in the phase 1b study and the RP2D for chidamide was determined to be 20 mg, twice a week. A total of 113 patients were treated at the RP2D in the phase 2 study, and the overall response rate was 60.2%, with a complete response rate of 40.7%. At a median follow-up of 36 months, the median PFS was 10.7 months, with 1-, 2-, and 3-year PFS rates of 49.9%, 38.0%, and 32.8%, respectively. The Chi-CHOEP regimen was well-tolerated, with grade 3/4 neutropenia occurring in approximately two-thirds of the patients. No unexpected adverse events (AEs) were reported and the observed AEs were manageable.
CONCLUSIONS: This large cohort phase 1b/2 study showed that Chi-CHOEP was well-tolerated with modest efficacy in previously untreated PTCL patients.
方法:前瞻性,多中心,单臂,进行了1b/2期研究。2016年3月至2019年11月,共纳入128例未经治疗的PTCL患者(18-70岁),并采用Chi-CHOEP方案治疗6个周期。在1b期研究中,评估西达本胺的3个剂量水平,主要终点是确定最大耐受剂量和推荐的2期剂量(RP2D)。2期研究的主要终点是2年无进展生存期(PFS)。
结果:1b期研究纳入了15例患者,西达本胺的RP2D测定为20mg,一周两次.在2期研究中,共有113名患者在RP2D接受治疗,总有效率为60.2%,完全缓解率为40.7%。在中位随访36个月时,中位PFS为10.7个月,1-,2-,3年PFS率为49.9%,38.0%,和32.8%,分别。Chi-CHOEP方案耐受性良好,大约三分之二的患者发生3/4级中性粒细胞减少症。未报告意外不良事件(AE),观察到的AE是可控的。
结论:这项大型队列1b/2期研究表明,Chi-CHOEP在先前未经治疗的PTCL患者中具有良好的耐受性,且疗效适中。