Service d'Oncologie Médicale, Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand, France.
Service de Thérapie Cellulaire et d'Hématologie Clinique Adulte, Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand, France
BMJ Open. 2023 May 2;13(5):e068480. doi: 10.1136/bmjopen-2022-068480.
Allogeneic haematopoietic stem-cell transplantation (allo-HSCT) is a major treatment for many haematological malignancies. The procedure has a good success rate but high transplant-related toxicity (TRM). TRM is mostly related to graft-versus-host disease (GvHD) and infectious complications. Alterations of the intestinal microbiota plays a major role in the development of allo-HSCT complications. The gut microbiota could be restored by faecal microbiota transplantation (FMT). However, there are no published randomised studies assessing the efficacy of FMT for GvHD prophylaxis.
This prospective, open-label, multi-centre, parallel-group, randomised phase-II clinical trial has been designed to assess the effect of FMT on toxicity in patients treated with myeloablative allo-HSCT for haematological malignancy. Based on Fleming's single-stage sample size estimation procedure, the design plans to include 60 male and female patients aged 18 or over per arm, to be randomly assigned to two groups, one with and one without (control group) FMT. The primary endpoint is GvHD-free relapse-free survival rate at 1 year after allo-HSCT. Secondary endpoints are outcome measures of the impact of FMT on allo-HSCT-related morbidity and mortality (overall survival and progression-free survival at 1 and 2 years, haematological parameters, infectious complications, tolerance and safety of FMT). The primary endpoint will be evaluated according to assumptions of the single-stage Fleming design, compared between groups by a log-rank test and further investigated in a multivariate marginal structural Cox model taking into account centre effect. The proportional-hazard hypothesis will be verified using Schoenfeld's test and by plotting residuals.
The local institutional review board (CPP Sud-Est II, France) issued approval on 27 January 2021. The French national authorities issued approval on 15 April 2021. The outcome of the study will be disseminated via peer-reviewed publications and at congresses.
NCT04935684.
异基因造血干细胞移植（allo-HSCT）是许多血液系统恶性肿瘤的主要治疗方法。该方法成功率高，但移植相关毒性（TRM）高。TRM 主要与移植物抗宿主病（GvHD）和感染性并发症有关。肠道微生物群的改变在 allo-HSCT 并发症的发展中起着重要作用。粪便微生物群移植（FMT）可恢复肠道微生物群。然而，目前尚无评估 FMT 预防 GvHD 疗效的随机研究发表。
本前瞻性、开放标签、多中心、平行组、随机二期临床试验旨在评估 FMT 对接受清髓性 allo-HSCT 治疗血液系统恶性肿瘤患者的毒性作用。根据 Fleming 单阶段样本量估计程序，该设计计划纳入每臂 60 名年龄在 18 岁及以上的男性和女性患者，随机分为两组，一组接受 FMT（治疗组），一组不接受（对照组）。主要终点是 allo-HSCT 后 1 年时无 GvHD 无复发存活率。次要终点是 FMT 对 allo-HSCT 相关发病率和死亡率（1 年和 2 年时的总生存率和无进展生存率、血液学参数、感染并发症、FMT 的耐受性和安全性）的影响的结果测量。主要终点将根据单阶段 Fleming 设计的假设进行评估，通过对数秩检验比较组间差异，并进一步通过考虑中心效应的多变量边际结构 Cox 模型进行分析。将通过 Schoenfeld 检验和绘制残差来验证比例风险假设。
当地机构审查委员会（法国 Sud-Est II 地区）于 2021 年 1 月 27 日批准。法国国家当局于 2021 年 4 月 15 日批准。该研究的结果将通过同行评议的出版物和会议进行传播。
NCT04935684。
