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 | Recruiting Phase 2 DMC

• 1 other identifier: RC23_0286
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 3

Brief 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

Keywords

Hematopoietic stem cell allograft (Allo-CSH); Methotrexate (MTX); Post-transplant cyclophosphamide (PTCY)

Outcome Measures

Primary Outcomes (1)

• Incidence of grade 3-4 acute GVHD following allo-CSH for all patients and for each conditioning group (Baltimore and TBF).

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

  Post-transplant through study completion, an average of 1 year

Secondary Outcomes (13)

• Incidence of engraftment

  Month 1 post-transplant

• Overall survival (OS)

  Post-transplant through study completion, an average of 1 year

• Disease-free survival (DFS)

  Post-transplant through study completion, an average of 1 year

• GVHD and relapse-free survival (GRFS)

  Post-transplant through study completion, an average of 1 year

• Incidence of acute GVHD grade 2-4

  Post-transplant through study completion, an average of 1 year

Study Arms (2)

(CLO)-BALTIMORE

EXPERIMENTAL

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

Drug: Methotrexate; Drug: Post-Transplant Cyclophosphamide; Drug: Fludarabine; Drug: Cycophosphamide; Drug: Anti-Thymoglobulin; Radiation: total body irradiation; Other: hematopoietic stem cells; Other: Graft nuclear cells; Other: Donor Lymphocytes Injection; Drug: Clofarabine

TBF

ACTIVE COMPARATOR

Conditioning regimen for LYMPHOID AND MYELOID HEMOPATHY

Drug: Methotrexate; Drug: Post-Transplant Cyclophosphamide; Drug: Anti-Thymoglobulin; Other: hematopoietic stem cells; Other: Graft nuclear cells; Other: Donor Lymphocytes Injection; Drug: Thiotepa; Drug: Busulfan; Drug: Fludarabine

Interventions

Methotrexate DRUG

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

Also known as: MTX

(CLO)-BALTIMORE; TBF

Post-Transplant Cyclophosphamide DRUG

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

Also known as: CY

(CLO)-BALTIMORE; TBF

Fludarabine DRUG

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)

Also known as: Fludarabine Baltimore

(CLO)-BALTIMORE

Cycophosphamide DRUG

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

(CLO)-BALTIMORE

Anti-Thymoglobulin DRUG

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

Also known as: ATG

(CLO)-BALTIMORE; TBF

total body irradiation RADIATION

2 grays on Day-1 before graft (=Day0)

Also known as: TBI

(CLO)-BALTIMORE

hematopoietic stem cells OTHER

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

Also known as: HSC

(CLO)-BALTIMORE; TBF

Graft nuclear cells OTHER

Graft nuclear cells CD3+ cells if needed after transplantation

(CLO)-BALTIMORE; TBF

Donor Lymphocytes Injection OTHER

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

Also known as: DLI

(CLO)-BALTIMORE; TBF

Clofarabine DRUG

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)

(CLO)-BALTIMORE

Thiotepa DRUG

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

TBF

Busulfan DRUG

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

TBF

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: ≥ 18 and ≤ 70 years old
• Patient with hematologic malignancy
• Indication for HSC allograft with attenuated conditioning
• Pluripotent stem cell (PSC) engraftment
• Availability of a 10/10 familial or non-familial HLA compatible donor
• Consent to the protocol
• ECOG \<=2
• Woman of childbearing age with negative pregnancy test and on highly effective contraception during treatment and for a period of 12 months after stopping MTX and CY
• Man of childbearing age with highly effective contraception during treatment and for a period of 6 months after stopping MTX and CY and a period of 12 months after stopping MTX and CY if TBF conditioning regimen arm
• Negative Hepatitis B, C, HIV serologies
• Social security affiliation

You may not qualify if:

• History of allograft
• Patient eligible for myeloablative conditioning (MAC)
• Bone marrow transplant
• Other progressive cancerous disease, or antecedent of cancer in the last five years, with the exception of a carcinoma of the skin or a carcinoma in situ of the uterine cole treated and in remission.
• Progressive psychiatric condition
• Pregnant or breastfeeding woman,
• Woman or man of childbearing age with lack of effective contraception
• Serious and uncontrolled concomitant infection
• Cardiac: systolic ejection fraction \< 50% by transthoracic ultrasound or by isotopic method (isotope gamma angiography), NYHA II, III or IV heart failure, active rhythmic, valvular or ischemic heart disease or anteriority
• Respiratory with EFR: DLCOc \<40% of theoretical
• Renal: creatinine clearance \< 50 ml/min (assessment with MDRD method)
• Urological: active urinary tract infection, history of acute urothelial toxicity due to cytotoxic chemotherapy or radiotherapy, known obstruction of urinary flow, pre-existing hemorrhagic cystitis
• Hepatic: transaminases greater than 5 times normal or bilirubin greater than 2 times normal
• Person protected by law (major under guardianship, curatorship or legal protection)
• Vaccination against yellow fever in the last year

Sponsors & Collaborators

• Nantes University Hospital: lead

Study Sites (3)

CHU Angers

Angers, France

RECRUITING

CHU Brest

Brest, France

RECRUITING

CHU Nantes

Nantes, France

RECRUITING

MeSH Terms

Conditions

Graft vs Host Disease; Hematologic Neoplasms

Interventions

Methotrexate; fludarabine; Whole-Body Irradiation; Clofarabine; Thiotepa; Busulfan

Condition Hierarchy (Ancestors)

Immune System Diseases; Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Radiotherapy; Therapeutics; Investigative Techniques; Adenine Nucleotides; Purine Nucleotides; Purines; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides; Phosphoramides; Organophosphorus Compounds; Organic Chemicals; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Sylvain THEPOT, MD

  Angers University Hospital

  PRINCIPAL INVESTIGATOR

• Marie-Anne COUTURIER, MD

  University Hospital, Brest

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amandine LE BOURGEOIS, MD

CONTACT

02 40 08 32 71; amandine.lebourgeois@chu-nantes.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: January 24, 2024
• First Posted: February 12, 2024
• Study Start: July 18, 2024
• Primary Completion (Estimated): October 18, 2027
• Study Completion (Estimated): July 18, 2028
• Last Updated: January 26, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (3)