Clinical trial NCT03359980: Treatment of Steroid Refractory Gastro-intestinal Acute GVHD afteR AllogeneiC HSCT With fEcal Microbiota tranSfer
Official title: Treatment of Steroid Refractory Gastro-intestinal Acute Graft-versus-Host disEase afteR AllogeneiC Hematopoietic Stem celL Transplantation With fEcal Microbiota tranSfer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Fecal Microbiota Transplantation
Lead sponsor: MaaT Pharma
Sponsor class: INDUSTRY
First posted: 2017-12-02
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Efficacy of FMT in the treatment of Steroid Refractory -Gastro-intestinal Acute GVHD (SR-GI-aGVHD) at D28 post inclusion
timeFrame: up to 4 weeks post inclusion
Secondary outcomes:
measure: Safety of FMT in patients with SR-GI-aGVHD
timeFrame: through study completion, an average of six months
measure: Gastrointestinal GVHD overall response rate at D28 post inclusion
timeFrame: Day 28
measure: Number of patients with infectious disorders
timeFrame: through study completion, an average of six months
measure: Number of multidrug resistant bacteria in faeces
timeFrame: through study completion, an average of six months
measure: Number of patients with Chronic GVHD
timeFrame: through study completion, an average of six months
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU Amiens
city: Angers
country: France
facility: CHU Angers
city: Besançon
country: France
facility: CHRU Besançon
city: Créteil
country: France
facility: Hôpital Henri Mondor
city: Lille
country: France
facility: CHRU Lille
city: Limoges
country: France
facility: CHU Limoges
city: Nantes
country: France
facility: CHU Nantes
city: Paris
country: France
facility: Hôpital Saint Antoine
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon Sud
city: Saint-Priest-en-Jarez
country: France
facility: Institut de Cancérologie de la Loire
city: Strasbourg
country: France
facility: CHU Strasbourg
city: Toulouse
country: France
facility: IUCT Oncopole
city: Roma
country: Italy
facility: Gemelli Hospital
city: Gdańsk
country: Poland
facility: Klinika Hematologii i Transplantologii
city: Katowice
country: Poland
facility: Public Clinic Hospital
city: Wroclaw
country: Poland
facility: University Clinical hospital
Study officials:
affiliation: Hôpital Saint Antoine - PARIS
name: Florent Malard, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: