Treatment of Steroid Refractory Gastro-intestinal Acute GVHD afteR AllogeneiC HSCT With fEcal Microbiota tranSfer

Study Overview
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Brief Summary
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Patients who have a gastrointestinal acute Graft versus host disease (GVHD) received a first-line standard treatment of corticosteroids. For patients who do not respond or progress after an initial response have a high mortality. There is an interest in identifying effective second line therapy for these patients corticosteroid-resistant acute GVHD. Fecal microbiota transfer might be a beneficial treatment in this clinical situation with a poor prognosis and limited therapeutic options.

Official Title
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Treatment of Steroid Refractory Gastro-intestinal Acute Graft-versus-Host disEase afteR AllogeneiC Hematopoietic Stem celL Transplantation With fEcal Microbiota tranSfer

Conditions
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Fecal Microbiota Transplantation

Intervention / Treatment
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* Drug: fecal microbiota transfer


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who develop a first episode of Stage 2 to 4 Gastro-intestinal Acute Graft-versus-Host (GI-aGVHD) with gut predominance (Przepiorka D, 1995), resistant to a first line therapy with steroids (lack of improvement after 5 days or progression after 3 days of treatment with corticosteroids at 2 mg/Kg methylprednisolone equivalent dose) (SR GI-aGVHD) Age ≥ 18 years old Allogeneic Hematopoietic stem cell transplantation (Allo-HSCT) with any type of donor, stem cell source, GVHD prophylaxis or conditioning regimen Patients able to have a minimum of 12 hours discontinuation of systemic antibiotics in order to perform the allogeneic FMT Signature of informed and written consent by the subject or by the subject's legally acceptable representative Exclusion Criteria: Grade IV hyper-acute GVHD Overlap chronic GVHD Acute GVHD after donor lymphocytes infusion Relapsed/persistent malignancy requiring rapid immune suppression withdrawal Active uncontrolled infection according to the attending physician Other systemic drugs than corticosteroids for GVHD treatment (including extra-corporeal photopheresis). Drugs already being used for GVHD prevention (eg. calcineurin inhibitors) are allowed. Absolute neutrophil count < 0.5 x 10^9 /L Absolute platelet count < 10 000 Patient Epstein-Barr Virus (EBV) negative Evidence of toxic megacolon or gastrointestinal perforation on abdominal X-ray Known allergy or intolerance to trehalose or maltodextrin Pregnancy: positive urinary or blood test in female of childbearing potential; lactation; absence of effective contraceptive method for female of childbearing potential Other ongoing interventional protocol that might interfere with the current study primary endpoint.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: treated patients<br>Treated with Fecal Microbiota Transfer (FMT) | Drug: fecal microbiota transfer<br>* transfer of fecal microbiota from healthy donors to the patients<br>* Other names: MaaT013;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of FMT in the treatment of Steroid Refractory -Gastro-intestinal Acute GVHD (SR-GI-aGVHD) at D28 post inclusion | Proportion of patients achieving GI and overall GVHD response by D28, defined as Complete response (CR) or Very Good Partial Response (VGPR) | up to 4 weeks post inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of FMT in patients with SR-GI-aGVHD | The overall safety of the study will be evaluated with the incidence of all Adverse Events (AEs) and Serious Adverse Events (SAEs) (frequency, grade, relationship) throughout the study period | through study completion, an average of six months | 
| Gastrointestinal GVHD overall response rate at D28 post inclusion | Proportion of patients achieving GI and overall GVHD response by D28, defined as Complete response (CR) or Very Good Partial Response (VGPR) or Partial Response (PR) | Day 28 | 
| Number of patients with infectious disorders | Evaluation of FMT activity on infectious disorders | through study completion, an average of six months | 
| Number of multidrug resistant bacteria in faeces | Evaluation of FMT activity on multidrug-resistant bacteria (MDRB) carriage | through study completion, an average of six months | 
| Number of patients with Chronic GVHD | Chronic GVHD expression | through study completion, an average of six months |