Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Rare Diseases

Hematologic Neoplasms

Graft vs Host Disease

Hematologic Diseases

Homologous Wasting Disease

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Dermatologic Agents

Reproductive Control Agents

Anti-Infective Agents

Micronutrients

Hematinics

Vitamins

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Methotrexate

Thymoglobulin

Busulfan

Thiotepa

Clofarabine

Antilymphocyte Serum

Vidarabine

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antimetabolites

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Antiviral Agents

Folinic Acid

Folate

Vitamin B9

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

Spots Global Cancer Trial Database for cycophosphamide