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

NCT03359980 | Completed Phase 2

• 1 other identifier: MPOH03
• Study Type: interventional
• Target: 24
• Locations: 3 countries
• Sites: 16

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.

Conditions

Fecal Microbiota Transplantation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Safety of FMT in patients with SR-GI-aGVHD

  through study completion, an average of six months

• Gastrointestinal GVHD overall response rate at D28 post inclusion

  Day 28

• Number of patients with infectious disorders

  through study completion, an average of six months

• Number of multidrug resistant bacteria in faeces

  through study completion, an average of six months

• Number of patients with Chronic GVHD

  through study completion, an average of six months

Study Arms (1)

treated patients

EXPERIMENTAL

Treated with Fecal Microbiota Transfer (FMT)

Drug: fecal microbiota transfer

Interventions

fecal microbiota transfer DRUG

transfer of fecal microbiota from healthy donors to the patients

Also known as: MaaT013

treated patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• MaaT Pharma: lead

Study Sites (16)

CHU Amiens

Amiens, 80054, France

Location

CHU Angers

Angers, 49933, France

Location

CHRU Besançon

Besançon, 25030, France

Location

Hôpital Henri Mondor

Créteil, 94000, France

Location

CHRU Lille

Lille, 59037, France

Location

CHU Limoges

Limoges, 87000, France

Location

CHU Nantes

Nantes, 44000, France

Location

Hôpital Saint Antoine

Paris, 75012, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69310, France

Location

Institut de Cancérologie de la Loire

Saint-Priest-en-Jarez, 42270, France

Location

CHU Strasbourg

Strasbourg, 67098, France

Location

IUCT Oncopole

Toulouse, 31100, France

Location

Gemelli Hospital

Roma, 168, Italy

Location

Klinika Hematologii i Transplantologii

Gdansk, 80-952, Poland

Location

Public Clinic Hospital

Katowice, 40-032, Poland

Location

University Clinical hospital

Wroclaw, 50-556, Poland

Location

Related Publications (1)

• Malard F, Loschi M, Huynh A, Cluzeau T, Guenounou S, Legrand F, Magro L, Orvain C, Charbonnier A, Panz-Klapuch M, Desmier D, Mear JB, Cornillon J, Robin C, Daguindau E, Bilger K, Vehreschild MJGT, Chevallier P, Labussiere-Wallet H, Mediavilla C, Couturier MA, Bulabois CE, Camus V, Chantepie S, Ceballos P, Gaugler B, Holler E, Dore J, Prestat E, Gasc C, Plantamura E, Mohty M. Pooled allogeneic faecal microbiota MaaT013 for steroid-resistant gastrointestinal acute graft-versus-host disease: a single-arm, multicentre phase 2 trial. EClinicalMedicine. 2023 Jul 26;62:102111. doi: 10.1016/j.eclinm.2023.102111. eCollection 2023 Aug.

  PMID: 37654670 DERIVED

MeSH Terms

Interventions

Fecal Microbiota Transplantation

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Study Officials

• Florent Malard, MD, PhD

  Hôpital Saint Antoine - PARIS

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2017
• First Posted: December 2, 2017
• Study Start: August 13, 2018
• Primary Completion: February 25, 2020
• Study Completion: November 26, 2020
• Last Updated: February 23, 2021

Record last verified: 2021-02

Locations

IT (1); PL (3); FR (12)