Allogeneic DiseasePhase 3MTX-aGVHDNCT03371667

To Compare the Efficacy of the Addition of Methotrexate (MTX) to Current Standard Acute Graft-versus-host Disease (GVHD) First-line Treatment With Corticosteroids

A Phase 3 study testing Methotrexate in people with Allogeneic Disease and GVH - Graft Versus Host Reaction, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Phase III randomized double-blinded trial designed to compare the efficacy of the addition of MTX to current standard acute GVHD first-line treatment with corticosteroids. The protocol will use a novel endpoint for benchmarking interventions based on a composite primary endpoint of GVHD-free and corticosteroids-free… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Allogeneic Disease, GVH - Graft Versus Host Reaction, GVHD, Acute
What is being tested?: Methotrexate
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 104 participants
Where: 1 siteFrance
Study dates: 16 Aug 2018to 24 Jan 2025
Phase: Phase 3
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

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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.

Who cannot join

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

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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

Trial locations and contacts

1 site in 1 country.

France1 site

Saint Antoine Hospital - Hematology Department
Paris, 75012

Other trials in France

About this study

Official title: A Multi-center Randomized in Double-blinded Phase III Study Comparing Standard Care Therapy Alone Versus Corticosteroids and Low-dose Methotrexate (MTX) for the First-line Treatment of Acute Graft-versus-host Disease After Allogeneic Stem Cell Transplantation

The primary endpoint of the trial will be the assessment of a composite endpoint of graft-versus-host disease-free and corticosteroids-free survival at 12 months after randomization

Read the detailed description

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.

Conditions: Allogeneic Disease, GVH - Graft Versus Host Reaction, GVHD, Acute, Stem Cell Transplant Complications
Being tested: Methotrexate, Placebo
Keywords: Hematopoietic Stem Cell, Methotrexate, Corticosteroids therapy, Acute GVHD, Allogenic stem cell transplantation
Medical subject headings: Graft vs Host Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MethotrexateDrug
Methotrexate 3 mg/m2 will be given once week for 4 weeks, then 3 mg/m2 every two weeks for 12 weeks. Body surface area will be capped at 2 m2.
Methotrexate will be given as an IV infusion over 15 minutes. All patients will received prednisone 2 mg/kg.day PO (or methylprednisolone 1.6 mg/Kg/day) for 3 days.
For responding patients between day 4 and 28, the dose of prednisone must be at least 0.25 mg/kg/day prednisone (or 0.2 mg/kg/day methylprednisolone).
All patients should receive a folinic acid supplementation 24 hours after each MTX/placebo administration.
Lederfoldin 10 mg po or iv will be administered on days 2, 9, 16 and 23. Lederfoldin 10 mg po or iv will be administered on days 37, 51, 65, 79, 93 and 103.
PlaceboDrug
Placebo 3 mg/m2 will be given once week for 4 weeks, then 3 mg/m2 every two weeks for 12 weeks. Body surface area will be capped at 2 m2.
Placebo will be given as an IV infusion over 15 minutes. All patients will received prednisone 2 mg/kg.day PO (or methylprednisolone 1.6 mg/Kg/day) for 3 days.
For responding patients between day 4 and 28, the dose of prednisone must be at least 0.25 mg/kg/day prednisone (or 0.2 mg/kg/day methylprednisolone).
All patients should receive a folinic acid supplementation 24 hours after each MTX/placebo administration.
Lederfoldin 10 mg po or iv will be administered on days 2, 9, 16 and 23. Lederfoldin 10 mg po or iv will be administered on days 37, 51, 65, 79, 93 and 103.

Study groups in NCT03371667
Study group	Role	What they receive
Methotrexate	Experimental	* 3mg/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 Receives: Drug: Methotrexate
Placebo	Placebo comparator	* 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 Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Assessment of a composite endpoint of graft-versus-host disease-free at 12 months after randomization.
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Measured: Evaluation will be performed at time of inclusion
Assessment of a composite endpoint of graft-versus-host disease-free at 12 months after randomization (1).
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Measured: Evaluation will be performed before start of MTX at the randomization.
Assessment of a composite endpoint of graft-versus-host disease-free at 12 months after randomization (2).
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Measured: Evaluation will be performed at Day 8
Assessment of a composite endpoint of graft-versus-host disease-free at 12 months after randomization (3).
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Measured: Evaluation will be performed at Day 15
Assessment of a composite endpoint of graft-versus-host disease-free at 12 months after randomization (4).
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Measured: Evaluation will be performed at Day 22
Assessment of a composite endpoint of graft-versus-host disease-free at 12 months after randomization (5).
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Measured: Evaluation will be performed at Day 28
Assessment of a composite endpoint of graft-versus-host disease-free at 12 months after randomization (6).
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Measured: Evaluation will be performed at Day 36
Assessment of a composite endpoint of graft-versus-host disease-free at 12 months after randomization (7).
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Measured: Evaluation will be performed at Day 50
Assessment of a composite endpoint of graft-versus-host disease-free at 12 months after randomization (8).
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Measured: Evaluation will be performed at Day 56
Assessment of a composite endpoint of graft-versus-host disease-free at 12 months after randomization (9).
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Measured: Evaluation will be performed at Day 64
Assessment of a composite endpoint of graft-versus-host disease-free at 12 months after randomization (10)
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Measured: Evaluation will be performed at Day 78
Assessment of a composite endpoint of graft-versus-host disease-free at 12 months after randomization (11).
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Measured: Evaluation will be performed at Day 92
Assessment of a composite endpoint of graft-versus-host disease-free at 12 months after randomization (12).
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Measured: Evaluation will be performed at Day 102
Assessment of a composite endpoint of graft-versus-host disease-free at 12 months after randomization (13).
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Measured: Evaluation will be performed at 5 months after randomization.
Assessment of a composite endpoint of graft-versus-host disease-free at 12 months after randomization (14).
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Measured: Evaluation will be performed at 6 months after randomization.
Assessment of a composite endpoint of graft-versus-host disease-free at 12 months after randomization (17).
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Measured: Evaluation will be performed at 9 months after randomization .
Assessment of a composite endpoint of graft-versus-host disease-free at 12 months after randomization (18).
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Measured: Evaluation will be performed at 12 months after randomization.
Assessment of a composite endpoint of corticosteroids-free survival at 12 months after randomization (19).
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Measured: Evaluation will be performed at time of inclusion.
Assessment of a composite endpoint of corticosteroids-free survival at 12 months after randomization (20).
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Measured: Evaluation will be performed before start of MTX at the randomization.
Assessment of a composite endpoint of corticosteroids-free survival at 12 months after randomization (21).
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Measured: Evaluation will be performed at Day 8.
Assessment of a composite endpoint of corticosteroids-free survival at 12 months after randomization (20).
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Measured: Evaluation will be performed at Day 15.
Assessment of a composite endpoint of corticosteroids-free survival at 12 months after randomization (21).
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Measured: Evaluation will be performed at Day 22.
Assessment of a composite endpoint of corticosteroids-free survival at 12 months after randomization (22).
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Measured: Evaluation will be performed at Day 28.
Assessment of a composite endpoint of corticosteroids-free survival at 12 months after randomization (23).
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Measured: Evaluation will be performed at Day 36
Assessment of a composite endpoint of corticosteroids-free survival at 12 months after randomization (24).
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Measured: Evaluation will be performed at Day 50.
Assessment of a composite endpoint of corticosteroids-free survival at 12 months after randomization (25).
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Measured: Evaluation will be performed at Day 56.
Assessment of a composite endpoint of corticosteroids-free survival at 12 months after randomization (26).
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Measured: Evaluation will be performed at Day 64.
Assessment of a composite endpoint of corticosteroids-free survival at 12 months after randomization (27).
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Measured: Evaluation will be performed at Day 78.
Assessment of a composite endpoint of corticosteroids-free survival at 12 months after randomization (28).
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Measured: Evaluation will be performed at D92.
Assessment of a composite endpoint of corticosteroids-free survival at 12 months after randomization (29).
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Measured: Evaluation will be performed at Day 102.
Assessment of a composite endpoint of corticosteroids-free survival at 12 months after randomization (30).
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Measured: Evaluation will be performed at 5 months after randomization.
Assessment of a composite endpoint of corticosteroids-free survival at 12 months after randomization (31).
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Measured: Evaluation will be performed at 6 months after randomization.
Assessment of a composite endpoint of corticosteroids-free survival at 12 months after randomization (32).
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Measured: Evaluation will be performed at 9 months after randomization.
Assessment of a composite endpoint of corticosteroids-free survival at 12 months after randomization (33).
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Measured: Evaluation will be performed at 12 months after randomization.

Secondary outcomes (11)

The incidence of severe adverse events within the first 12 months after randomization
Measured: 12 months after randomization
The proportion of complete remission (CR), very good partial response (VGPR), partial response (PR), mixed response (MR), no response (NR) and progression at day 28, day 56 and best response within the first 12 months after randomization.
Measured: at day 28, day 56 and best response within the first 12 months after randomization.
The proportion of GVHD flare within the first 12 months after randomization.
Measured: 12 months after randomization
Cumulative incidence of overall and severe chronic GVHD as assessed by NIH Consensus Criteria within the first 12 months after randomization(Jagasia, Greinix et al. 2015, Lee, Wolff et al. 2015).
Measured: within the first 12 months after randomization
Incidence of systemic of infection and CMV(cytomegalovirus ) reactivation within 3 months after randomization
Measured: within 3 months after randomization
Incidence of EBV (Epstein-Barr virus) reactivation and post-transplant lymphoproliferative disease within 12 months after randomization
Measured: within 12 months after randomization
Cumulative incidence of non-relapse mortality within the first 12 months after randomization.
Measured: 12 months after randomization
Corticosteroids-free, disease-free and overall survival within the first 12 months after randomization.
Measured: 12 months after randomization
Immune recovery and microbiota: number of patients with complete immune recovery (lymphocytes and dendritic cells) and correction of microbiota dysbiosis within the first 12 months
Measured: 12 months after randomization
Quality of Life (QoL)-1
Evaluation by 1 questionnaire: EORTC QLQ-C30 (quality of life questionnaire) (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30)
Measured: 12 Months
Quality of Life (QoL)-2
Evaluation by 1 questionnaire: FACT-BMT (Functional Assessment of Cancer Therapy - Bone Marrow Transplant)
Measured: 12 Months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

16 Aug 201824 Jan 2025

First posted13 Dec 2017
Study start16 Aug 2018
Primary completion24 Jan 2025
Study completion24 Jan 2025

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Allogeneic DiseaseStudies of the same condition, open and under way.
More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 104 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03371667
Sponsor's protocol ID: PHRC-K 16-150
Other IDs: 2017-002691-98, 2017
Acronym: MTX-aGVHD
Status last verified: Sep 2026
First submitted: 31 Jul 2017
Last updated: 18 Sep 2026
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Undecided

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 18 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multi-center Randomized in Double-blinded Phase III Study Comparing Standard Care Therapy Alone Versus Corticosteroids and Low-dose Methotrexate (MTX) for the First-line Treatment of Acute Graft-versus-host Disease After Allogeneic Stem Cell Transplantation
ClinicalTrials.gov ID: NCT03371667
Acronym / sponsor ID: MTX-aGVHD / PHRC-K 16-150
Conditions: Allogeneic Disease, GVH - Graft Versus Host Reaction, GVHD, Acute, Stem Cell Transplant Complications
Keywords: Hematopoietic Stem Cell, Methotrexate, Corticosteroids therapy, Acute GVHD, Allogenic stem cell transplantation
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 104 participants (actual)
Lead sponsor: Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
Study start: 16 Aug 2018 (actual)
Primary completion: 24 Jan 2025 (actual)
Study completion: 24 Jan 2025 (actual)
First posted: 13 Dec 2017 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The primary endpoint of the trial will be the assessment of a composite endpoint of graft-versus-host disease-free and corticosteroids-free survival at 12 months after randomization

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
Methotrexate	Experimental	Drug: Methotrexate* 3mg/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	Placebo comparator	Drug: 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

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (10 listed)

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

Key exclusion criteria (15 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
MethotrexateMethotrexate 3 mg/m2 will be given once week for 4 weeks, then 3 mg/m2 every two weeks for 12 weeks. Body surface area will be capped at 2 m2. Methotrexate will be given as an IV infusion over 15 minutes. All patients will received prednisone 2 mg/kg.day PO (or methylprednisolone 1.6 mg/Kg/day) for 3 days. For responding patients between day 4 and 28, the dose of prednisone must be at least 0.25 mg/kg/day prednisone (or 0.2 mg/kg/day methylprednisolone). All patients should receive a folinic acid supplementation 24 hours after each MTX/placebo administration. Lederfoldin 10 mg po or iv will be administered on days 2, 9, 16 and 23. Lederfoldin 10 mg po or iv will be administered on days 37, 51, 65, 79, 93 and 103.	Drug	Methotrexate
PlaceboPlacebo 3 mg/m2 will be given once week for 4 weeks, then 3 mg/m2 every two weeks for 12 weeks. Body surface area will be capped at 2 m2. Placebo will be given as an IV infusion over 15 minutes. All patients will received prednisone 2 mg/kg.day PO (or methylprednisolone 1.6 mg/Kg/day) for 3 days. For responding patients between day 4 and 28, the dose of prednisone must be at least 0.25 mg/kg/day prednisone (or 0.2 mg/kg/day methylprednisolone). All patients should receive a folinic acid supplementation 24 hours after each MTX/placebo administration. Lederfoldin 10 mg po or iv will be administered on days 2, 9, 16 and 23. Lederfoldin 10 mg po or iv will be administered on days 37, 51, 65, 79, 93 and 103.	Drug	Placebo

Primary outcome

Assessment of a composite endpoint of graft-versus-host disease-free at 12 months after randomization.
Time frame: Evaluation will be performed at time of inclusion
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Assessment of a composite endpoint of graft-versus-host disease-free at 12 months after randomization (1).
Time frame: Evaluation will be performed before start of MTX at the randomization.
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Assessment of a composite endpoint of graft-versus-host disease-free at 12 months after randomization (2).
Time frame: Evaluation will be performed at Day 8
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Assessment of a composite endpoint of graft-versus-host disease-free at 12 months after randomization (3).
Time frame: Evaluation will be performed at Day 15
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Assessment of a composite endpoint of graft-versus-host disease-free at 12 months after randomization (4).
Time frame: Evaluation will be performed at Day 22
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Assessment of a composite endpoint of graft-versus-host disease-free at 12 months after randomization (5).
Time frame: Evaluation will be performed at Day 28
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Assessment of a composite endpoint of graft-versus-host disease-free at 12 months after randomization (6).
Time frame: Evaluation will be performed at Day 36
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Assessment of a composite endpoint of graft-versus-host disease-free at 12 months after randomization (7).
Time frame: Evaluation will be performed at Day 50
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Assessment of a composite endpoint of graft-versus-host disease-free at 12 months after randomization (8).
Time frame: Evaluation will be performed at Day 56
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Assessment of a composite endpoint of graft-versus-host disease-free at 12 months after randomization (9).
Time frame: Evaluation will be performed at Day 64
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Assessment of a composite endpoint of graft-versus-host disease-free at 12 months after randomization (10)
Time frame: Evaluation will be performed at Day 78
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Assessment of a composite endpoint of graft-versus-host disease-free at 12 months after randomization (11).
Time frame: Evaluation will be performed at Day 92
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Assessment of a composite endpoint of graft-versus-host disease-free at 12 months after randomization (12).
Time frame: Evaluation will be performed at Day 102
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Assessment of a composite endpoint of graft-versus-host disease-free at 12 months after randomization (13).
Time frame: Evaluation will be performed at 5 months after randomization.
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Assessment of a composite endpoint of graft-versus-host disease-free at 12 months after randomization (14).
Time frame: Evaluation will be performed at 6 months after randomization.
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Assessment of a composite endpoint of graft-versus-host disease-free at 12 months after randomization (17).
Time frame: Evaluation will be performed at 9 months after randomization .
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Assessment of a composite endpoint of graft-versus-host disease-free at 12 months after randomization (18).
Time frame: Evaluation will be performed at 12 months after randomization.
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Assessment of a composite endpoint of corticosteroids-free survival at 12 months after randomization (19).
Time frame: Evaluation will be performed at time of inclusion.
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Assessment of a composite endpoint of corticosteroids-free survival at 12 months after randomization (20).
Time frame: Evaluation will be performed before start of MTX at the randomization.
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Assessment of a composite endpoint of corticosteroids-free survival at 12 months after randomization (21).
Time frame: Evaluation will be performed at Day 8.
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Assessment of a composite endpoint of corticosteroids-free survival at 12 months after randomization (20).
Time frame: Evaluation will be performed at Day 15.
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Assessment of a composite endpoint of corticosteroids-free survival at 12 months after randomization (21).
Time frame: Evaluation will be performed at Day 22.
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Assessment of a composite endpoint of corticosteroids-free survival at 12 months after randomization (22).
Time frame: Evaluation will be performed at Day 28.
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Assessment of a composite endpoint of corticosteroids-free survival at 12 months after randomization (23).
Time frame: Evaluation will be performed at Day 36
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Assessment of a composite endpoint of corticosteroids-free survival at 12 months after randomization (24).
Time frame: Evaluation will be performed at Day 50.
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Assessment of a composite endpoint of corticosteroids-free survival at 12 months after randomization (25).
Time frame: Evaluation will be performed at Day 56.
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Assessment of a composite endpoint of corticosteroids-free survival at 12 months after randomization (26).
Time frame: Evaluation will be performed at Day 64.
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Assessment of a composite endpoint of corticosteroids-free survival at 12 months after randomization (27).
Time frame: Evaluation will be performed at Day 78.
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Assessment of a composite endpoint of corticosteroids-free survival at 12 months after randomization (28).
Time frame: Evaluation will be performed at D92.
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Assessment of a composite endpoint of corticosteroids-free survival at 12 months after randomization (29).
Time frame: Evaluation will be performed at Day 102.
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Assessment of a composite endpoint of corticosteroids-free survival at 12 months after randomization (30).
Time frame: Evaluation will be performed at 5 months after randomization.
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Assessment of a composite endpoint of corticosteroids-free survival at 12 months after randomization (31).
Time frame: Evaluation will be performed at 6 months after randomization.
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Assessment of a composite endpoint of corticosteroids-free survival at 12 months after randomization (32).
Time frame: Evaluation will be performed at 9 months after randomization.
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.
Assessment of a composite endpoint of corticosteroids-free survival at 12 months after randomization (33).
Time frame: Evaluation will be performed at 12 months after randomization.
GVHD-free survival is defined as absence of initiation of additional GVHD therapy or development of chronic GVHD requiring systemic therapy, and corticosteroids-free survival as absence of continuation of corticosteroids above a dose of 0.15 mg/Kg day.

11 secondary outcomes

The incidence of severe adverse events within the first 12 months after randomization
Time frame: 12 months after randomization
The proportion of complete remission (CR), very good partial response (VGPR), partial response (PR), mixed response (MR), no response (NR) and progression at day 28, day 56 and best response within the first 12 months after randomization.
Time frame: at day 28, day 56 and best response within the first 12 months after randomization.
The proportion of GVHD flare within the first 12 months after randomization.
Time frame: 12 months after randomization
Cumulative incidence of overall and severe chronic GVHD as assessed by NIH Consensus Criteria within the first 12 months after randomization(Jagasia, Greinix et al. 2015, Lee, Wolff et al. 2015).
Time frame: within the first 12 months after randomization
Incidence of systemic of infection and CMV(cytomegalovirus ) reactivation within 3 months after randomization
Time frame: within 3 months after randomization
Incidence of EBV (Epstein-Barr virus) reactivation and post-transplant lymphoproliferative disease within 12 months after randomization
Time frame: within 12 months after randomization
Cumulative incidence of non-relapse mortality within the first 12 months after randomization.
Time frame: 12 months after randomization
Corticosteroids-free, disease-free and overall survival within the first 12 months after randomization.
Time frame: 12 months after randomization
Immune recovery and microbiota: number of patients with complete immune recovery (lymphocytes and dendritic cells) and correction of microbiota dysbiosis within the first 12 months
Time frame: 12 months after randomization
Quality of Life (QoL)-1
Time frame: 12 Months
Quality of Life (QoL)-2
Time frame: 12 Months

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2026.
Individual participant dataSharing planned: Undecided

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Mohamad Mohty, PU-PH principal investigator

Assistance Publique - Hôpitaux de Paris

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Methotrexate in people with Allogeneic Disease and GVH - Graft Versus Host Reaction, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Assessment of a composite endpoint of graft-versus-host disease-free at 12 months after randomization. (time frame: Evaluation will be performed at time of inclusion). The study lists 34 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03371667.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2026.