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

NCT ID: NCT06252870

Last Updated: 2024-10-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

82 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-07-18

Study Completion Date

2028-07-18

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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

See the medical conditions and disease areas that this research is targeting or investigating.

Graft Versus Host Disease Hematologic Malignancy

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

(CLO)-BALTIMORE

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

Group Type EXPERIMENTAL

Methotrexate

Intervention Type 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)

Post-Transplant Cyclophosphamide

Intervention Type DRUG

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

Fludarabine

Intervention Type 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)

Cycophosphamide

Intervention Type DRUG

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

Anti-Thymoglobulin

Intervention Type DRUG

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

total body irradiation

Intervention Type RADIATION

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

hematopoietic stem cells

Intervention Type OTHER

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

Graft nuclear cells

Intervention Type OTHER

Graft nuclear cells CD3+ cells if needed after transplantation

Donor Lymphocytes Injection

Intervention Type OTHER

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

Clofarabine

Intervention Type 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)

TBF

Conditioning regimen for LYMPHOID AND MYELOID HEMOPATHY

Group Type ACTIVE_COMPARATOR

Methotrexate

Intervention Type 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)

Post-Transplant Cyclophosphamide

Intervention Type DRUG

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

Anti-Thymoglobulin

Intervention Type DRUG

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

hematopoietic stem cells

Intervention Type OTHER

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

Graft nuclear cells

Intervention Type OTHER

Graft nuclear cells CD3+ cells if needed after transplantation

Donor Lymphocytes Injection

Intervention Type OTHER

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

Thiotepa

Intervention Type DRUG

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

Busulfan

Intervention Type DRUG

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

Fludarabine

Intervention Type DRUG

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

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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)

Intervention Type DRUG

Post-Transplant Cyclophosphamide

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

Intervention Type 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)

Intervention Type DRUG

Cycophosphamide

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

Intervention Type DRUG

Anti-Thymoglobulin

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

Intervention Type DRUG

total body irradiation

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

Intervention Type RADIATION

hematopoietic stem cells

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

Intervention Type OTHER

Graft nuclear cells

Graft nuclear cells CD3+ cells if needed after transplantation

Intervention Type OTHER

Donor Lymphocytes Injection

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

Intervention Type OTHER

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)

Intervention Type DRUG

Thiotepa

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

Intervention Type DRUG

Busulfan

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

Intervention Type DRUG

Fludarabine

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

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

MTX CY Fludarabine Baltimore ATG TBI HSC DLI Fludarabine TBF

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 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

Exclusion Criteria

* 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
* Known or suspected hypersensitivity to rabbit proteins as well as to the active substance and excipients of all investigational and ancillary drugs administered during the study,
* Contraindication to any of the investigational or adjuvant drugs administered during the study
* Patient not speaking French
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Nantes University Hospital

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Sylvain THEPOT, MD

Role: PRINCIPAL_INVESTIGATOR

Angers University Hospital

Marie-Anne COUTURIER, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Brest

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

CHU Angers

Angers, , France

Site Status RECRUITING

CHU Brest

Brest, , France

Site Status RECRUITING

CHU Nantes

Nantes, , France

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

France

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Amandine LE BOURGEOIS, MD

Role: CONTACT

02 40 08 32 71 ext. +33

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Sylvain THEPOT, MD

Role: primary

0241354482 ext. +33

Marie-Anne COUTURIER, MD

Role: primary

0298223765 ext. +33

Amandine LE BOURGEOIS, MD

Role: primary

0240083271 ext. +33

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

RC23_0286

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.