Overview

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