Fecal Microbiota Transplantation
Conditions
Brief summary
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.
Interventions
transfer of fecal microbiota from healthy donors to the patients
Sponsors
MaaT Pharma
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of FMT in the treatment of Steroid Refractory -Gastro-intestinal Acute GVHD (SR-GI-aGVHD) at D28 post inclusion | up to 4 weeks post inclusion | Proportion of patients achieving GI and overall GVHD response by D28, defined as Complete response (CR) or Very Good Partial Response (VGPR) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety of FMT in patients with SR-GI-aGVHD | through study completion, an average of six months | 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 |
| Gastrointestinal GVHD overall response rate at D28 post inclusion | Day 28 | 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) |
| Number of patients with infectious disorders | through study completion, an average of six months | Evaluation of FMT activity on infectious disorders |
| Number of multidrug resistant bacteria in faeces | through study completion, an average of six months | Evaluation of FMT activity on multidrug-resistant bacteria (MDRB) carriage |
| Number of patients with Chronic GVHD | through study completion, an average of six months | Chronic GVHD expression |
Countries
France, Italy, Poland
Outcome results
None listed