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COMPLETED

NCT03371667

PHASE3

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

Sponsor: Assistance Publique - Hôpitaux de Paris

View on ClinicalTrials.gov

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 survival. 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

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

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

104

Start Date

2018-08-16

Completion Date

2025-01-24

Last Updated

2026-09-18

Healthy Volunteers

Conditions

Allogeneic Disease GVH - Graft Versus Host Reaction GVHD, Acute Stem Cell Transplant Complications

Interventions

DRUG

Methotrexate

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.

DRUG

Placebo

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.

Inclusion Criteria: * 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. Exclusion Criteria: * 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

Locations (1)

Saint Antoine Hospital - Hematology Department

Paris, France