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

• Status: Recruiting
• Trial end date: 2022-07-01
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris
• Treatments: Methotrexate

Criteria

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