Faecal Microbiota Transplantation for Prevention of Graft-versus-host Sisease After Allogeneic Stem Cell Transplantation for Haematological Malignancies
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 150
- 试验地点
- 22
- 主要终点
- Graft-versus-host disease and Relapse-Free Survival (GRFS) rate after allogeneic hematopoietic stem cell transplantation
研究概览
简要总结
The aim of this study is to assess the Fecal Microbiota Transplantation (FMT) efficacy in the prevention of allogeneic hematopoietic stem cell transplantation (allo-HSCT) complications and particularly Graft versus Host Disease (GvHD).
The hypothesis of this study is that allogeneic FMT may improve outcomes of these patients.
详细描述
The TMF-Allo study is a prospective, open-label, multi-center, parallel, randomized phase II clinical trial comparing a group patients with FMT and a control group of patients without FMT.
The main objective of this study is to assess the effect of allogeneic FMT versus no treatment on Graft-versus-host disease and Relapse-Free Survival (GRFS) at one year in adult patients treating with myelo-ablative allo-HSCT for haematologic malignancy.
The secondary objectives are to evaluate :
- Overall survival, progression-free survival at 1 and 2 years,
- The haematological evolution,
- The evolution of infections,
- The tolerance and safety of the TMF carried out in post-transplant,
- The evolution of the composition and diversity of the microbiota in allograft patients receiving TMF or not.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient aged 18 or over
- •Men and women
- •Patients affiliated with a social-security organization
- •Patients undergoing a myelo-ablative allo-HSCT for a controlled haematologic malignant disease, with peripheral stem cells, whatever the type of donor (except cord blood)
- •Signed and dated informed consent
排除标准
- •Status of tumor progression at the time of allo-HSCT
- •Inability to understand the protocol (linguistic barrier, cognitive difficulties)
- •Medical history of another progressive cancer or occurrence in the 3 previous years (excluding basal cell carcinoma)
- •Presence of a simultaneous serious and uncontrolled disease (severe cardiac, renal, hepatic or respiratory failure, severe sepsis)
- •Fecal incontinence
- •Participation in another clinical trial studying an allograft procedure including the type of graft, the type of immunosuppression, a preventive or a curative treatment of GvHD, or studying the effectiveness of a FMT in another indication.
- •Pregnant women
- •Patient under guardianship, curatorship or protection of justice
研究组 & 干预措施
Group 1: Fecal Microbiota Transplantation (FMT)
Patients randomized in the "FMT group" will received FMT. FMT product will be made by the the pharmacy of the Clermont-Ferrand University Hospital from stools of healthy volunteer donors within 6 hours after defecation in order to preserve the viability of the bacteria. The preparation will be standardized: 50g aliquots will be prepared and diluted in 250mL of 0.9% NaCl containing 10% glycerol, until a homogeneous suspension is obtained. The preparation will be rapidly frozen at -80°C until use, with a maximum shelf life of 18 months.
干预措施: Fecal Microbiota Transplantation (Drug)
结局指标
主要结局
Graft-versus-host disease and Relapse-Free Survival (GRFS) rate after allogeneic hematopoietic stem cell transplantation
时间窗: at Day 360 after allogeneic hematopoietic stem cell transplantation
GRFS is a composite endpoint of GvHD-free/relapse-free survival in which events include grade II-IV acute GvHD, moderate and severe chronic GvHD, relapse, or death in the first year post-HSCT. GRFS will be measured at one year after allo-HSCT and compared between both groups of patients.
次要结局
- Haematopoietic reconstitution(At the time of haematopoietic reconstitution)
- Transplant-Related Mortality(At Day 180, Day 360 and Day 720 after allogeneic hematopoietic stem cell transplantation)
- Analysis the intestinal microbiota in patients(Before the conditioning regimen, before the FMT and at Day 30, Day 90 and Day 360 after white blood cells recovery)
- Overall survival(At Day 360 and Day 720 after allogeneic hematopoietic stem cell transplantation)
- Progression-free survival(At Day 360 and Day 720 after allogeneic hematopoietic stem cell transplantation)
- Engraftment rates(At Day 30, Day 60, Day 90, Day 180, Day 360 and Day 720 after allogeneic hematopoietic stem cell transplantationday)
- Cumulative incidence of infections(At Day 360 after allogeneic hematopoietic stem cell transplantation)
- Severe infections description(From the day of inclusion to Day 360 after allogeneic hematopoietic stem cell transplantation)
- Quality of life assessment(at Day -7, Day 30, Day 90, Day 180, Day 360 and Day 720 after allogeneic hematopoietic stem cell transplantation)
- Impact of Fecal Microbiota Transplantation (FMT) on multi-resistant bacteria, extended-spectrum beta-lactamases and Clostridium difficile infection(At Day 360 after allogeneic hematopoietic stem cell transplantation)
- Unexpected event description that could be in relation with FMT of Fecal Microbiota Transplantation (FMT)(From the day of FMT to Day 360 after allogeneic hematopoietic stem cell transplantation)
- Blood collection for a metabolomic study in stool donnors(At the time of the first stool donnation between Day 7 to Day 55 after the inclusion)
- Blood collection for an analysis of anti-microbiota IgG and IgA in stool donnors(At the time of the first stool donnation between Day 7 to Day 55 after the inclusion)
- Stool collection for an analysis of the virome in patients(Before the conditioning regimen, before the FMT and at Day 30, Day 90 and Day 360 after white blood cells recovery)
- Stool collection for an analysis of the virome in stool donnors(At the time of the first stool donnation between Day 7 to Day 55 after the inclusion)
- Analysis the intestinal microbiota in stool donnors(At the time of the first stool donnation between Day 7 to Day 55 after the inclusion)
- Blood collection for a metabolomic study in patients(Before the conditioning regimen, before the FMT and at Day 30, Day 90 and Day 360 after white blood cells recovery)
- Blood collection for an analysis of anti-microbiota IgG and IgA in patients(Before the conditioning regimen, before the FMT and at Day 30, Day 90 and Day 360 after white blood cells recovery)
- Cumulative incidence of acute GvHD(At Day 360 after allogeneic hematopoietic stem cell transplantation)
- Cumulative incidence of chronic GvHD(At Day 720 after allogeneic hematopoietic stem cell transplantation)