Clinical trial NCT04935684: Faecal Microbiota Transplantation After Allogeneic Stem Cell Transplantation
Official title: Faecal Microbiota Transplantation for Prevention of Graft-versus-host Sisease After Allogeneic Stem Cell Transplantation for Haematological Malignancies
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Acute Leukemia in Remission
Myelodysplastic Syndromes
Myeloproliferative Syndrome
Hodgkin Lymphoma
Lymphoma, Non-Hodgkin
Myeloma
Chronic Lymphocytic Leukemia
Keywords: Allogeneic hematopoietic stem cell transplantation
Hematologic malignancies
Graft versus Host Disease
Intestinal microbiota
Intestinal dysbiosis
Fecal Microbiota Transplantation
Lead sponsor: University Hospital, Clermont-Ferrand
Sponsor class: OTHER
Collaborators: name: Ministry of Health, France
name: French Society of Hematology
First posted: 2021-06-23
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A group patients will receive Fecal Microbiota Transplantation (FMT) within 4 weeks following neutrophils recovery after the allogeneic hematopoietic stem cell transplantation procedure and a control group of patients will not receive FMT.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Graft-versus-host disease and Relapse-Free Survival (GRFS) rate after allogeneic hematopoietic stem cell transplantation
timeFrame: at Day 360 after allogeneic hematopoietic stem cell transplantation
Secondary outcomes:
measure: Overall survival
timeFrame: At Day 360 and Day 720 after allogeneic hematopoietic stem cell transplantation
measure: Progression-free survival
timeFrame: At Day 360 and Day 720 after allogeneic hematopoietic stem cell transplantation
measure: Haematopoietic reconstitution
timeFrame: At the time of haematopoietic reconstitution
measure: Engraftment rates
timeFrame: At Day 30, Day 60, Day 90, Day 180, Day 360 and Day 720 after allogeneic hematopoietic stem cell transplantationday
measure: Cumulative incidence of acute GvHD
timeFrame: At Day 360 after allogeneic hematopoietic stem cell transplantation
measure: Cumulative incidence of chronic GvHD
timeFrame: At Day 720 after allogeneic hematopoietic stem cell transplantation
measure: Transplant-Related Mortality
timeFrame: At Day 180, Day 360 and Day 720 after allogeneic hematopoietic stem cell transplantation
measure: Cumulative incidence of infections
timeFrame: At Day 360 after allogeneic hematopoietic stem cell transplantation
measure: Severe infections description
timeFrame: From the day of inclusion to Day 360 after allogeneic hematopoietic stem cell transplantation
measure: Impact of Fecal Microbiota Transplantation (FMT) on multi-resistant bacteria, extended-spectrum beta-lactamases and Clostridium difficile infection
timeFrame: At Day 360 after allogeneic hematopoietic stem cell transplantation
measure: Unexpected event description that could be in relation with FMT of Fecal Microbiota Transplantation (FMT)
timeFrame: From the day of FMT to Day 360 after allogeneic hematopoietic stem cell transplantation
measure: Quality of life assessment
timeFrame: at Day -7, Day 30, Day 90, Day 180, Day 360 and Day 720 after allogeneic hematopoietic stem cell transplantation
measure: Analysis the intestinal microbiota in patients
timeFrame: Before the conditioning regimen, before the FMT and at Day 30, Day 90 and Day 360 after white blood cells recovery
measure: Analysis the intestinal microbiota in stool donnors
timeFrame: At the time of the first stool donnation between Day 7 to Day 55 after the inclusion
measure: Blood collection for a metabolomic study in patients
timeFrame: Before the conditioning regimen, before the FMT and at Day 30, Day 90 and Day 360 after white blood cells recovery
measure: Blood collection for an analysis of anti-microbiota IgG and IgA in patients
timeFrame: Before the conditioning regimen, before the FMT and at Day 30, Day 90 and Day 360 after white blood cells recovery
measure: Blood collection for a metabolomic study in stool donnors
timeFrame: At the time of the first stool donnation between Day 7 to Day 55 after the inclusion
measure: Blood collection for an analysis of anti-microbiota IgG and IgA in stool donnors
timeFrame: At the time of the first stool donnation between Day 7 to Day 55 after the inclusion
measure: Stool collection for an analysis of the virome in patients
timeFrame: Before the conditioning regimen, before the FMT and at Day 30, Day 90 and Day 360 after white blood cells recovery
measure: Stool collection for an analysis of the virome in stool donnors
timeFrame: At the time of the first stool donnation between Day 7 to Day 55 after the inclusion
Other outcomes:
Locations:
city: Amiens
country: France
facility: Service d'Hématologie Clinique et Thérapie Cellulaire CHU Amiens Picardie - Site Sud
city: Angers
country: France
facility: Service Maladies du sang CHU Angers
city: Besançon
country: France
facility: Hématologie clinique CHU Besançon
city: Clermont-Ferrand
country: France
facility: Plateforme d'Investigation Clinique / Centre d'Investigation Clinique - Inserm 1405, CHU Gabriel Montpied Clermont-Ferrand
city: Clermont-Ferrand
country: France
facility: Service de thérapie Cellulaire et d'Hématologie Clinique Adulte CHU Estaing - Clermont-Ferrand
city: Grenoble
country: France
facility: Service hématologie CHU Grenoble
city: Lille
country: France
facility: Service des Maladies du sang Hôpital HURIEZ, CHRU de Lille
city: Limoges
country: France
facility: Service de thérapie cellulaire et l'hématologie clinique adulte CHU Limoges
city: Lyon
country: France
facility: Service d'Hématologie Centre Hospitalier Lyon Sud
city: Nancy
country: France
facility: Service d'Hématologie et de Médecine interne Hôpital Brabois CHRU Nancy
city: Nantes
country: France
facility: Service d'Hématologie Clinique CHU Nantes
city: Nice
country: France
facility: Service d'hématologie clinique, département de greffe de moelle CHU Nice
city: Paris
country: France
facility: Service d'Hématologie Adultes Hôpital Necker
city: Paris
country: France
facility: Service d'Hématologie clinique Hôpital Pitié-Salpêtrière
city: Paris
country: France
facility: Service d'hématologie greffe Hôpital St Louis
city: Pessac
country: France
facility: Hématologie clinique et thérapie cellulaire Hôpital Haut-Lévèque
city: Poitiers
country: France
facility: Service d'hématologie greffe Hôpital St Louis
city: Rouen
country: France
facility: Département d'hématologie CAC Rouen
city: Saint-Étienne
country: France
facility: Hématologie clinique Institut de Cancérologie de la Loire
city: Toulouse
country: France
facility: IUC T - Oncopôle
Study officials:
affiliation: University Hospital, Clermont-Ferrand
name: Jacques-Olivier BAY, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Groupe hospitalier Pitié-Salpêtrière, Paris
name: Stéphanie NGUYEN, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: