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

Phase 2
Completed
Conditions
Fecal Microbiota Transplantation
Interventions
Drug: fecal microbiota transfer
Registration Number
NCT03359980
Lead Sponsor
MaaT Pharma
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
24
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
treated patientsfecal microbiota transferTreated with Fecal Microbiota Transfer (FMT)
Primary Outcome Measures
NameTimeMethod
Efficacy of FMT in the treatment of Steroid Refractory -Gastro-intestinal Acute GVHD (SR-GI-aGVHD) at D28 post inclusionup 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 Outcome Measures
NameTimeMethod
Number of patients with Chronic GVHDthrough study completion, an average of six months

Chronic GVHD expression

Gastrointestinal GVHD overall response rate at D28 post inclusionDay 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 multidrug resistant bacteria in faecesthrough study completion, an average of six months

Evaluation of FMT activity on multidrug-resistant bacteria (MDRB) carriage

Safety of FMT in patients with SR-GI-aGVHDthrough 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

Number of patients with infectious disordersthrough study completion, an average of six months

Evaluation of FMT activity on infectious disorders

Trial Locations

Locations (16)

CHU Amiens

🇫🇷

Amiens, France

CHU Limoges

🇫🇷

Limoges, France

CHRU Besançon

🇫🇷

Besançon, France

Gemelli Hospital

🇮🇹

Roma, Italy

Klinika Hematologii i Transplantologii

🇵🇱

Gdańsk, Poland

CHU Strasbourg

🇫🇷

Strasbourg, France

Hôpital Henri Mondor

🇫🇷

Créteil, France

Public Clinic Hospital

🇵🇱

Katowice, Poland

Institut de Cancérologie de la Loire

🇫🇷

Saint-Priest-en-Jarez, France

IUCT Oncopole

🇫🇷

Toulouse, France

CHU Angers

🇫🇷

Angers, France

CHRU Lille

🇫🇷

Lille, France

CHU Nantes

🇫🇷

Nantes, France

Centre Hospitalier Lyon Sud

🇫🇷

Pierre-Bénite, France

Hôpital Saint Antoine

🇫🇷

Paris, France

University Clinical hospital

🇵🇱

Wroclaw, Poland

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