NCT06252870

Study Testing Two Conditioning Regimen With a Single Prophylaxis of GVHD by Cyclophosphamide and Methotrexate Post-transplant in Patients Eligible for Matched-donor Allograft Transplantation

Randomized Phase 2 Study Testing Two Conditioning Regimen With a Single Prophylaxis of Graft-versus-host Disease by Cyclophosphamide and Methotrexate Post-transplant in Patients Eligible for Matched-donor Allograft Transplantation

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 82 (estimated)
• Sponsor: Nantes University Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (allo-CSH). Recently, in the context of semi-identical (=haploidentical) HLA donors, but also of compatible HLA donors, the use of cyclophosphamide (CY) administered in high doses at early post-transplant (PT) (=PTCY) (Days +3 and +4 or +5) has shown excellent control of acute and chronic GVH, even enabling the discontinuation of other immunosuppressive drugs administered after allo-CSH (ciclosporin, mycophenolate mofetyl (MMF) or Cellcept). This step has already been taken in the context of allo-CSH with myeloablative conditioning (MAC), which is a minoritary conditioning in adults. However, in the context of allo-CSH with reduced-intensity conditioning (RIC), which predominates in adults, this strategy seems insufficient to prevent the risk of GVHD. The idea of reducing the use of immunosuppressants in the context of RIC/HLA-compatible transplants seems, however, still relevant, in order to reduce their adverse effects, improve patients' quality of life and enhance the reconstitution of the post-transplant immune system.

Detailed description

For this reason, the investigators now wish to test the administration of a combination of a high dose of early post-transplant CY (PTCY) and methotrexate (MTX) on days (D) D+1, D+4, D+6, D+11 (doses already performed in MAC transplant prophylaxis), with anti-lymphocyte serum (ALS) with RIC conditioning, without ciclosporin or MMF. The investigators hypothesize that administration of this PTCY+MTX combination will enable immunosuppressive drugs to be discontinued as early as D+11 post-transplant, compared with the usual average of 3 to 4 months.

Conditions

• Graft Versus Host Disease
• Hematologic Malignancy

Interventions

Type	Name	Description
DRUG	Methotrexate	15 mg/m² on Day+1 after graft (=Day0) 10 mg/m² 3 days on Day+4/Day+6/Day+11 after graft (=Day0)
DRUG	Post-Transplant Cyclophosphamide	50 mg/kg intravenous 2 days on Day+3/Day+5 after graft (=Day0)
DRUG	Fludarabine	Conditioning regimen: 30 mg/m² Intravenous 5 days from Day-6 to Day-2 (Day-6/Day-5-/Day-4/Day-3/Day-2 before graft (=Day0)
DRUG	Cycophosphamide	Conditioning regimen: 14.5 mg/kg intravenous 2 days on Day-6/Day-5 before graft (=Day0)
DRUG	Anti-Thymoglobulin	Conditioning regimen: 2.5 mg/kg intravenous on Day-2 before graft (=Day0)
RADIATION	total body irradiation	2 grays on Day-1 before graft (=Day0)
OTHER	hematopoietic stem cells	High dose of hematopoietic stem cells derived from peripheral blood on transplantation day (=Day0 graft)
OTHER	Graft nuclear cells	Graft nuclear cells CD3+ cells if needed after transplantation
OTHER	Donor Lymphocytes Injection	DLI with CD3+ if relapse after transplantation or in prevention of relapse
DRUG	Clofarabine	Conditioning regimen: 30 mg/m² Intravenous 5 days from Day-6 to Day-2 (Day-6/Day-5-/Day-4/Day-3/Day-2 before graft (=Day0)
DRUG	Thiotepa	Conditioning regimen: 5 mg/kg Intravenous at Day-6 before graft (=Day0)
DRUG	Busulfan	Conditioning regimen: 3.2 mg/kg Intravenous 2 days at Day-2 and Day-1 before graft (=Day0)
DRUG	Fludarabine	Conditioning regimen: 40 mg/m² intravenous 4 days on Day-5/Day-4/Day-3/Day-2 before graft (=Day0)

Timeline

• Start date: 2024-07-18
• Primary completion: 2027-10-18
• Completion: 2028-07-18
• First posted: 2024-02-12
• Last updated: 2026-01-26

Locations

3 sites across 1 country: France