Etude : MTX GvHD /

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

Situation thérapeutique : GvH

Traitement : Chimiothérapie

Cadre réglementaire : RIPH1

Dernière MÀJ : 23/12/2021
CIM10 - Localisation(s)
Informations principales
Titre : Etude de phase III randomisée, multicentrique, en double-insu comparant le méthotrexate (MTX) à faible dose et le traitement standard dans le traitement de première ligne de la réaction aigue du greffon contre l’hôte après allogreffe de cellules souches hématopoïétiques

Spécialité : Tissus lymphoïde, hématopoïétique et apparentés
Localisation : C96 - Tumeurs malignes des tissus lymphoïde, hématopoïétique et apparentés, autres et non précisées
Informations complémentaires
Schéma : This is a phase III randomized, multicenter, double blinded controlled study. Patients who develop clinically meaningful acute GVHD and who meet all other entry criteria will be randomized 1:1 to receive either corticosteroids and placebo ("standard of care", control arm) or the combination of low-dose MTX with corticosteroids as first-line therapy for acute GVHD (MTX; "experimental arm").

The primary analysis of this hypothesis generation study is to estimate the composite endpoint of GVHD-free and corticosteroids-free survival at 12 months after randomization in both treatment arms. In fact, it is more and more established that such composite endpoint is a clinically very relevant one because it represents ideal recovery from allo-SCT (Stem Cell transplantation) (at 1 year after acute GVHD diagnosis) and a measure of cure without ongoing morbidity.

2 arms:
- Experimental: Methotrexate
5mg/Kg/day methotrexate for 4 weeks then 3 mg/m2 every two weeks for 12 weeks
2mg/kg/day PO prednisone prednisone (or 1.6 mg/kg/day IV methylprednisolone) once daily.
10 mg po or iv lederfolin after each MTX administration
- Placebo Comparator: Placebo
Once a week placebo for 4 weeks then every two weeks for 12 weeks
2 mg/kg/day PO prednisone (or 1.6 mg/kg/day IV methylprednisolone) once daily.
10 mg po or iv lederfolin after each placebo administration

Phase : III

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 : - Adults patients (>=18 years old) with hematological diseases, who develop a first episode of acute GVHD (grade II-IV) requiring systemic therapy
- First allo-SCT, with any type of donor, stem cell source, GVHD prophylaxis or conditioning regimen
- Biopsy of acute GVHD target organ is recommended, but not required. Enrollment should not be delayed awaiting biopsy or pathology results
- The patient must have received no previous systemic immune suppressive therapy for treatment of acute GVHD, except for a maximum 72 hours of prior corticosteroid therapy
- Absolute neutrophil count (ANC) greater than 0.5 G/L
- Platelets count greater than 20 G/L
- Signed informed consent
- Affiliation to a social security system (recipient or assign)
- Women who are of childbearing potential must have a negative serum pregnancy test and agree to use a medically acceptable method of contraception until 6 months after the end of treatment.
- Men with a partner of childbearing potential must agree to use a medically acceptable method of contraception until 6 months after the end of treatment.

Critères de non-inclusion : - Hyper-acute GVHD as defined by the MD Anderson's criteria (Saliba, de Lima et al. 2007)
- Flare of GVHD in a patient already on corticosteroid treatment
- Overlap chronic GVHD as defined by the NIH Consensus Criteria (Jagasia, Greinix et al. 2015)
- MTX given within 7 days of enrollment
- Active uncontrolled infection
- Relapsed/persistent malignancy requiring rapid immune suppression withdrawal
- Acute GVHD after donor lymphocytes infusion (DLI)
- Other systemic drugs for GVHD treatment (including extra-corporeal photopheresis)
- If any prior steroid therapy (for indication other than GVHD), treatment at doses > 0.5 mg/kg/day methyl-prednisolone within 7 days prior to onset of acute GVHD
- Patients who are pregnant, breast feeding, or if sexually active, unwilling to use effective birth control for the duration of the study
- Patient on dialysis
- Patients with veno-occlusive disease of the liver or with significant liver abnormalities who in the judgment of the treating physician cannot receive MTX
- Patients requiring after inclusion in the protocol the continuation of one or more of the following medication: probenecide, trimethoprime (alone or in combination with sulfametoxazole), phenylbutazone or yellow fever vaccine
- Patients with a history of intolerance/allergy to MTX
- Hypersensitivity to the active substance or to any of the excipients
Informations relatives au promoteur
Promoteur :
Type de sponsor : Institutionnel
75010 PARIS 10

Coordonnateur :
Centre investigateur
Informations relatives aux investigateurs
Centre investigateur :
Institut d'Hématologie Bas-Normand (IHBN) - Avenue de la Cote de Nacre - 14000 CAEN

Investigateur :
Gandhi Laurent DAMAJ

Marie-Charlotte ZAPALOWICZ

Statut de l'essai : OUVERT

MAJ : 23/12/2020