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

Fecal Microbiota Transplantation Clinical Trial

— HERACLES  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03359980
• Other study ID #: MPOH03
• Status: Completed
• Phase: Phase 2
• Start date: August 13, 2018
• Est. completion date: November 26, 2020

Study information

• Verified date: February 2021
• Source: MaaT Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: November 26, 2020
• Est. primary completion date: February 25, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Fecal Microbiota Transplantation

Intervention

Drug:
• fecal microbiota transfer
transfer of fecal microbiota from healthy donors to the patients

Locations

Country	Name	City	State
France	CHU Amiens	Amiens
France	CHU Angers	Angers
France	CHRU Besançon	Besançon
France	Hôpital Henri Mondor	Créteil
France	CHRU Lille	Lille
France	CHU Limoges	Limoges
France	CHU Nantes	Nantes
France	Hôpital Saint Antoine	Paris
France	Centre Hospitalier Lyon Sud	Pierre-Bénite
France	Institut de Cancérologie de la Loire	Saint-Priest-en-Jarez
France	CHU Strasbourg	Strasbourg
France	IUCT Oncopole	Toulouse
Italy	Gemelli Hospital	Roma
Poland	Klinika Hematologii i Transplantologii	Gdansk
Poland	Public Clinic Hospital	Katowice
Poland	University Clinical hospital	Wroclaw

Sponsors (1)

Lead Sponsor	Collaborator
MaaT Pharma

Countries where clinical trial is conducted

France,  Italy,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Number of patients with infectious disorders	Evaluation of FMT activity on infectious disorders	through study completion, an average of six months
Secondary	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
Secondary	Number of patients with Chronic GVHD	Chronic GVHD expression	through study completion, an average of six months