Faecal Microbiota Transplantation for Prevention of Graft-versus-host Sisease After Allogeneic Stem Cell Transplantation for Haematological Malignancies
Overview
- Phase
- Phase 2
- Intervention
- Fecal Microbiota Transplantation
- Conditions
- Acute Leukemia in Remission
- Sponsor
- University Hospital, Clermont-Ferrand
- Enrollment
- 150
- Locations
- 19
- Primary Endpoint
- Graft-versus-host disease and Relapse-Free Survival (GRFS) rate after allogeneic hematopoietic stem cell transplantation
- Status
- Recruiting
- Last Updated
- 3 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
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.
Intervention: Fecal Microbiota Transplantation
Outcomes
Primary Outcomes
Graft-versus-host disease and Relapse-Free Survival (GRFS) rate after allogeneic hematopoietic stem cell transplantation
Time Frame: 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.
Secondary Outcomes
- Haematopoietic reconstitution(At the time of haematopoietic reconstitution)
- Cumulative incidence of chronic GvHD(At Day 720 after allogeneic hematopoietic stem cell transplantation)
- 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 acute GvHD(At Day 360 after allogeneic hematopoietic stem cell transplantation)
- 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)