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

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.

Conditions

• Graft Versus Host Disease
• Hematologic Malignancy

Interventions

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)

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

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)

Sponsors & Collaborators

• Nantes University Hospital

  lead OTHER

Principal Investigators

• Sylvain THEPOT, MD · Angers University Hospital

• Marie-Anne COUTURIER, MD · University Hospital, Brest

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-07-18

Primary Completion

2027-10-18

Completion

2028-07-18

Countries

• France

Study Locations