Evaluation of Allogeneic Fecal Microbiota Transplantation for Complication Prevention Post-Allogeneic Hematopoietic Stem Cell Transplantation in Hematologic Malignancies

The primary objective of this study is to evaluate the effect of **allogeneic fecal microbiota transplantation (FMT)** compared with no treatment on graft-versus-host disease-free, relapse-free survival (GRFS) at one year post-transplant in patients treated with myeloablative conditioning (MAC) allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematological malignancy. This is clinically relevant as it aims to improve post-transplant outcomes by potentially reducing the incidence of graft-versus-host disease (GvHD) and relapse, which are significant complications affecting survival and quality of life in these patients.

Secondary objectives include: - Evaluating the incidence of engraftment, acute and chronic GvHD, overall survival, progression-free survival, transplant-related mortality, quality of life, and the rate of severe infections. - Assessing the tolerance and safety of post-allo-HSCT FMT, its effect on multidrug-resistant bacteria/extended spectrum beta-lactamases (ESBL), and the cumulative incidence of Clostridium difficile infection and diarrhea. - Evaluating microbiota composition and diversity by 16s sequencing in all patients and donors at various time points before and after allo-HSCT and FMT.

The clinical trial involves **patients** who have undergone **allogeneic hematopoietic stem cell transplantation** (allo-HSCT) for various **haematological malignancies**. The study population includes both male and female participants aged 18 years and older. Participants are required to have undergone allo-HSCT with myeloablative conditioning and an allogeneic peripheral stem cell transplant, excluding cord blood, for a controlled haematological malignancy. All participants must be affiliated with a social security organization and have provided informed consent. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity.

The clinical trial is designed to evaluate the effect of **allogeneic faecal microbiota** transplantation (FMT) compared with no treatment on graft-versus-host disease-free, relapse-free survival (GRFS) at one year post-transplant in patients who have undergone myeloablative conditioning allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematological malignancies. This is a Phase 4, randomized, double-blind, controlled trial. The trial is expected to run from May 2022 to May 2027, with participant involvement lasting up to one year post-transplant.

Participants will be required to attend several study visits throughout the trial. The initial visit will be a screening visit to confirm eligibility based on criteria such as age (≥ 18 years), previous allo-HSCT for controlled hematological malignancy, and informed consent. Following the screening, participants will be randomized to receive either the FMT treatment or no treatment. Subsequent follow-up visits will be scheduled to monitor the primary endpoint of GRFS at one year, as well as secondary endpoints including overall and progression-free survival at one and two years, evaluation of hematological criteria, assessment of graft-versus-host disease (GVHD), incidence of infectious complications, tolerance and safety of post-allo-HSCT FMT, evolution of microbiota composition and diversity, and quality of life.

The end-of-study visit will occur at the conclusion of the one-year post-transplant period, where final assessments will be conducted. Participants may be withdrawn from the study early if they experience significant adverse events, withdraw consent, or if the investigator deems it necessary for their safety. The trial aims to provide valuable insights into the potential benefits of FMT in improving outcomes for patients undergoing allo-HSCT for hematological malignancies.

The clinical trial involves the use of an **experimental medication** known as "Transplant microbiote fécal," which is a **rectal suspension**. The active substance in this formulation is **allogeneic faecal microbiota**, classified as a structurally diverse substance. The medication is administered via **rectal use**. The dosage is set at a maximum of 250 ml per day, with the total dose not exceeding 250 ml over the course of the treatment period, which is limited to one day. This formulation is not a pediatric formulation and is not classified as an orphan drug. The product is identified by the sponsor product code "TMF" and is authorized for use in the trial.

In this study, there is no **non-experimental treatment** such as a placebo or comparator treatment being used. The trial aims to evaluate the effect of the allogeneic faecal microbiota transplantation compared to no treatment on graft-versus-host disease-free, relapse-free survival at one year post-transplant in patients undergoing myeloablative conditioning allogeneic hematopoietic stem cell transplantation for hematologic malignancy. Compliance with the dosing schedule will be monitored to ensure adherence to the protocol.

Efficacy in this clinical trial will be assessed primarily through the measurement of **GRFS (Graft-versus-host disease and Relapse-Free Survival)** rate at one year post-allograft. This primary endpoint will provide a direct evaluation of the treatment's impact on preventing complications associated with allogeneic hematopoietic stem cell transplantation in patients with hematologic malignancies. Secondary endpoints will include overall and progression-free survival at one and two years, evaluation of hematological criteria, assessment of graft-versus-host disease (GVHD), incidence of infectious complications, tolerance and safety of post-allo-HSCT fecal microbiota transplantation (FMT), evolution of the composition and diversity of the microbiota, and quality of life. These parameters will be measured and collected at specified timepoints throughout the trial to ensure comprehensive analysis. The trial aims to compare the effect of allogeneic FMT with no treatment, focusing on the prevention of complications and improvement of survival outcomes in the specified patient population.