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BALTIMORE conditioning regime for LYMPHOID HEMOPATHY CLO-BALTIMORE conditioning regime for MYELOID HEMOPATHY

Conditioning regimen for LYMPHOID AND MYELOID HEMOPATHY

15 mg/m² on Day+1 after graft (=Day0) 10 mg/m² 3 days on Day+4/Day+6/Day+11 after graft (=Day0)

50 mg/kg intravenous 2 days on Day+3/Day+5 after graft (=Day0)

Post-Transplant Cyclophosphamide

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)

Conditioning regimen: 14.5 mg/kg intravenous 2 days on Day-6/Day-5 before graft (=Day0)

Cycophosphamide

Conditioning regimen: 2.5 mg/kg intravenous on Day-2 before graft (=Day0)

Anti-Thymoglobulin

total body irradiation

High dose of hematopoietic stem cells derived from peripheral blood on transplantation day (=Day0 graft)

hematopoietic stem cells

Graft nuclear cells CD3+ cells if needed after transplantation

Graft nuclear cells

DLI with CD3+ if relapse after transplantation or in prevention of relapse

Donor Lymphocytes Injection

Conditioning regimen: 5 mg/kg Intravenous at Day-6 before graft (=Day0)

Conditioning regimen: 3.2 mg/kg Intravenous 2 days at Day-2 and Day-1 before graft (=Day0)

Conditioning regimen: 40 mg/m² intravenous 4 days on Day-5/Day-4/Day-3/Day-2 before graft (=Day0)

Amandine LE BOURGEOIS, MD

Sylvain THEPOT, MD

Marie-Anne COUTURIER, MD

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.

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.

Multicenter, phase 2, non-comparative, randomized, open-label, prospective drug trial

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

Estimation of the incidence of grade 3 and 4 acute GVHD following allo-CSH (excluding post-DLI\* acute GVHD) according to Mount Sinai criteria.

Engraftment assessed on hematological reconstitution (number of days of aplasia with PNN \<0.5 G/L and platelets \< 20 G/L, number of platelet and red cell concentrate transfusions)

survival between day 0 of transplantation and date of death or last follow-up

survival between day 0 of transplantation and date of relapse, death or last follow-up

relapse-free survival without grade 3-4 acute GVHD or chronic GVHD requiring systemic treatment

Acute GVH grade 2-4 according to Mount Sinai criteria

Acute corticoresistant GVHD according to the criteria of Mohty et al. defined by :

* worsening/progression of disease after 3 days of 2mg/kg/day systemic corticosteroid therapy with methylprednisolone (or equivalent),
* non-improvement of disease after 7 days of 2mg/kg/day systemic corticosteroid therapy with methylprednisolone (or equivalent),
* disease progression to a new organ after treatment with 1mg/kg/day methylprednisolone (or equivalent) in the case of cutaneous or gastrointestinal GVHD or,
* recurrence of acute GVHD during or after the corticosteroid reduction phase

any death unrelated to relapse or disease progression

Total donor or mixed chimerism. Total donor chimerism = result \>95% donor CD3+ cells. Mixed chimerism = result \>5% and \<95% donor CD3+ cells.

Grade 3 and 4 post-transplant adverse events (dates of occurrence) (NCI CTCAE criteria, version number 5)

Infections: viral (CMV, EBV, BKV, adenovirus), bacteriological, fungal and parasitic

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
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	NCT06252870	Graft Versus Ho... Hematologic Mal...	Methotrexate Post-Transplant... Fludarabine Cycophosphamide Anti-Thymoglobu... total body irra... hematopoietic s... Graft nuclear c... Donor Lymphocyt... Clofarabine Thiotepa Busulfan Fludarabine	18 Years - 70 Years	Nantes University Hospital
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	NCT06252870	Graft Versus Ho... Hematologic Mal...	Methotrexate Post-Transplant... Fludarabine Cycophosphamide Anti-Thymoglobu... total body irra... hematopoietic s... Graft nuclear c... Donor Lymphocyt... Clofarabine Thiotepa Busulfan Fludarabine	18 Years - 70 Years	Nantes University Hospital
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	NCT06252870	Graft Versus Ho... Hematologic Mal...	Methotrexate Post-Transplant... Fludarabine Cycophosphamide Anti-Thymoglobu... total body irra... hematopoietic s... Graft nuclear c... Donor Lymphocyt... Clofarabine Thiotepa Busulfan Fludarabine	18 Years - 70 Years	Nantes University Hospital

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