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Graft Versus Host DiseasePhase 2CY-MET-RICNCT06252870

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

A Phase 2 study testing Methotrexate, Post-Transplant Cyclophosphamide and Fludarabine in people with Graft Versus Host Disease and Hematologic Malignancy, run by Nantes University Hospital at 3 sites in France.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
Methotrexate, Post-Transplant Cyclophosphamide and Fludarabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
82 participants
Where
3 sitesFrance
Study dates
18 Jul 2024to 18 Jul 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 11Show fewer
  • 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

Who cannot join

  • 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,
Show all 18Show fewer
  • 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

Trial locations and contacts

3 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Amandine LE BOURGEOIS, MD contact

02 40 08 32 71 ext. +33

amandine.lebourgeois@chu-nantes.fr

France3 sites, 3 recruiting

  • CHU Angers

    Angers

    Sylvain THEPOT, MD, 0241354482 ext. +33, sylvain.thepot@chu-angers.fr

    Recruiting

  • CHU Brest

    Brest

    Marie-Anne COUTURIER, MD, 0298223765 ext. +33, marie-anne.couturier@chu-brest.fr

    Recruiting

  • CHU Nantes

    Nantes

    Amandine LE BOURGEOIS, MD, 0240083271 ext. +33, amandine.lebourgeois@chu-nantes.fr

    Recruiting

Other trials in France

About this study

Official title: 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

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).

Read more

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.

Read the detailed description

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.

Being tested
Methotrexate, Post-Transplant Cyclophosphamide, Fludarabine, Cycophosphamide, Anti-Thymoglobulin
Keywords
Hematopoietic stem cell allograft (Allo-CSH), Methotrexate (MTX), Post-transplant cyclophosphamide (PTCY)
Medical subject headings
Graft vs Host Disease, Hematologic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MethotrexateDrug

    Also called MTX

    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 CyclophosphamideDrug

    Also called CY

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

  • FludarabineDrug

    Also called Fludarabine Baltimore

    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)

  • CycophosphamideDrug

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

  • Anti-ThymoglobulinDrug

    Also called ATG

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

  • total body irradiationRadiation

    Also called TBI

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

  • hematopoietic stem cellsOther

    Also called HSC

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

  • Graft nuclear cellsOther

    Graft nuclear cells CD3+ cells if needed after transplantation

  • Donor Lymphocytes InjectionOther

    Also called DLI

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

  • ClofarabineDrug

    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)

  • ThiotepaDrug

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

  • BusulfanDrug

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

  • FludarabineDrug

    Also called Fludarabine TBF

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

Study groups in NCT06252870
Study groupRoleWhat they receive
(CLO)-BALTIMOREExperimentalBALTIMORE conditioning regime for LYMPHOID HEMOPATHY CLO-BALTIMORE conditioning regime for MYELOID HEMOPATHY
Receives: 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
TBFActive comparatorConditioning regimen for LYMPHOID AND MYELOID HEMOPATHY
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (13)

  1. Incidence of engraftment

    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)

    Measured: Month 1 post-transplant

  2. Overall survival (OS)

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

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

  3. Disease-free survival (DFS)

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

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

  4. GVHD and relapse-free survival (GRFS)

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

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

  5. Incidence of acute GVHD grade 2-4

    Acute GVH grade 2-4 according to Mount Sinai criteria

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

  6. Incidence of chronic GVHD

    Chronic GVHD according to NCI criteria

    Measured: From month 3 post-transplant through study completion, an average of 1 year

  7. Incidence of corticoresistant acute GVHD

    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

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

  8. Incidence of non-relapse mortality (NRM)

    any death unrelated to relapse or disease progression

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

  9. Incidence of relapse

    any documented disease recurrence

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

  10. Chimerism

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

    Measured: At Month1, Month2, Month3, Month6, Month12 post-transplant

  11. Immune reconstitution

    T, NK, B lymphocytes and monocytes

    Measured: At Month3, Month6, Month9, Month12 post-transplant

  12. Grade 3 and 4 post-transplant adverse events

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

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

  13. Incidence of viral, bacteriological, fungal and parasitic infections

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

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Feb 2024
  2. Study start18 Jul 2024
  3. Primary completion18 Oct 2027 (estimated)
  4. Study completion18 Jul 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Multicenter, phase 2, non-comparative, randomized, open-label, prospective drug trial
Masking
None (open label)
Enrolment
82 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06252870
Sponsor's protocol ID
RC23_0286
Acronym
CY-MET-RIC
Status last verified
Jan 2026
First submitted
24 Jan 2024
Last updated
26 Jan 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Methotrexate, Post-Transplant Cyclophosphamide and Fludarabine in people with Graft Versus Host Disease and Hematologic Malignancy, run by Nantes University Hospital at 3 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 26 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Amandine LE BOURGEOIS, MD (02 40 08 32 71 ext. +33, amandine.lebourgeois@chu-nantes.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of grade 3-4 acute GVHD following allo-CSH for all patients and for each conditioning group (Baltimore and TBF). (time frame: Post-transplant through study completion, an average of 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06252870.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jan 2026; AzTrials last refreshed its copy on 2 Nov 2026.

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