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

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

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.

Study Overview

• Status: Completed
• Conditions: Fecal Microbiota Transplantation
• Intervention / Treatment: Drug: fecal microbiota transfer

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Amiens, France, 80054
    • CHU Amiens
  • Angers, France, 49933
    • CHU Angers
  • Besançon, France, 25030
    • CHRU Besançon
  • Créteil, France, 94000
    • Hopital Henri Mondor
  • Lille, France, 59037
    • CHRU Lille
  • Limoges, France, 87000
    • CHU Limoges
  • Nantes, France, 44000
    • CHU Nantes
  • Paris, France, 75012
    • Hopital Saint Antoine
  • Pierre-Bénite, France, 69310
    • Centre Hospitalier Lyon Sud
  • Saint-Priest-en-Jarez, France, 42270
    • Institut de Cancerologie de La Loire
  • Strasbourg, France, 67098
    • CHU Strasbourg
  • Toulouse, France, 31100
    • IUCT Oncopole
• Italy
  • Roma, Italy, 168
    • Gemelli Hospital
• Poland
  • Gdańsk, Poland, 80-952
    • Klinika Hematologii i Transplantologii
  • Katowice, Poland, 40-032
    • Public Clinic Hospital
  • Wroclaw, Poland, 50-556
    • University Clinical Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: treated patients; Treated with Fecal Microbiota Transfer (FMT)	Drug: fecal microbiota transfer; transfer of fecal microbiota from healthy donors to the patients; Other Names: MaaT013

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: MaaT Pharma
• Investigators: Principal Investigator: Florent Malard, MD, PhD, Hopital Saint Antoine - Paris

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 13, 2018
• Primary Completion (ACTUAL): February 25, 2020
• Study Completion (ACTUAL): November 26, 2020

Study Registration Dates

• First Submitted: November 20, 2017
• First Submitted That Met QC Criteria: November 27, 2017
• First Posted (ACTUAL): December 2, 2017

Study Record Updates

• Last Update Posted (ACTUAL): February 23, 2021
• Last Update Submitted That Met QC Criteria: February 22, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: MPOH03

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No