Etude : HERACLES /

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Acronyme / Nom
Situation thérapeutique
Cadre réglementaire
Présentation de l'étude
Acronyme / Nom : HERACLES

Situation thérapeutique : GvH

Traitement :

Cadre réglementaire : RIPH1

Dernière MÀJ : 14/12/2021
CIM10 - Localisation(s)
Informations principales
Titre : Traitement de la maladie aigue du greffon contre l’hôte à prédominance digestive corticorésistante après allogreffe de cellules souches hématopoïétiques par Transfert de microbiote fécal.

Spécialité : Tissus lymphoïde, hématopoïétique et apparentés
Localisation : C96 - Tumeurs malignes des tissus lymphoïde, hématopoïétique et apparentés, autres et non précisées
Informations complémentaires
Schéma : 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.

Current Primary outcome:
Efficacy of FMT in the treatment of Steroid Refractory -Gastro-intestinal Acute GVHD (SR-GI-aGVHD) at D28 post inclusion [ Time Frame: up 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)

Current Secondary outcomes:
- Safety of FMT in patients with SR-GI-aGVHD [ Time Frame: through 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 disorders [ Time Frame: through study completion, an average of six months ]
- Evaluation of FMT activity on infectious disorders
- Number of multidrug resistant bacteria in faeces [ Time Frame: through study completion, an average of six months ]
- Evaluation of FMT activity on multidrug-resistant bacteria (MDRB) carriage
- Number of patients with Chronic GVHD [ Time Frame: through study completion, an average of six months ]

Study arm:
Experimental: treated patients
Treated with Fecal Microbiota Transfer (FMT) from healthy donor to the patients
Intervention: Drug: fecal microbiota transfer

Phase : II

Stade : NA

Informations libres de droit
Critères d'inclusion
Critères de non-inclusion
Informations libres de droit
Critères d'inclusion et de non-inclusion
Critères d'inclusion : - Patients who develop a first episode of Stage 3 or 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

Critères de non-inclusion : - Grade IV hyper-acute GVHD
- Late onset aGVHD
- 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 109 /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 or latex
- 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.
Informations relatives au promoteur
Promoteur :
Type de sponsor : Industriel

Coordonnateur :
Centre investigateur
Informations relatives aux investigateurs
Centre investigateur :
Centre Hospitalier Universitaire de Lille - 2 Avenue Oscar Lambret - 59000 LILLE

Investigateur :
Docteur Leonardo MAGRO

Secrétariat de recherche

Statut de l'essai : CLOS

MAJ : 22/04/2020