Informations générales (source: ClinicalTrials.gov)

NCT06083129 En recrutement IDF
Phase III Study Comparing GVHD Prophylaxis With ATG-thymoglobulin to ATLG-grafalon in Elderly Patients With Acute Myeloid Leukemia or Myelodysplasic Syndrome and Receiving an Allogeneic Hematopoietic Stem Cell Transplantation With a 10/10 HLA Matched Unrelated Donor Following a Reduced Intensity Conditioning Regimen by Fludarabine-treosulfan
Interventional
Phase 3
Assistance Publique - Hôpitaux de Paris (Voir sur ClinicalTrials)
novembre 2023
novembre 2028
03 mai 2026
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative therapy in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Most of the patients requiring an allo-HSCT are above 50 years of age and are transplanted with a reduced intensity conditioning (RIC) regimen. The optimal RIC and Graft Versus Host Disease (GVHD) prophylaxis regimen allowing a good control of the disease while preventing GVHD remains to be determined for elderly patients. A phase III trial comparing the conventional RIC fludarabine-busulfan 2 days to fludarabine-treosulfan demonstrated an advantage for the flu-treosulfan arm in terms of event free survival (EFS), that should therefore be considered as the new standard of RIC regimen for AML and MDS. GVHD prevention has a crucial role in post-transplant outcomes by potentially interfering with the graft-versus-leukemia (GVL) effect and immune reconstitution. Anti-thymocyte globulins (ATG) are recommended to reduce the risk of acute and chronic GVHD in transplants performed with matched unrelated donors. However, the optimal type of ATG between the 2 approved brands (ATG-thymoglobulin and ATLG-grafalon) displaying distinct characteristics and the optimal dose of ATG are still unknown. In a retrospective study of patients transplanted mainly with RIC with matched related and unrelated donors for haematological malignancies, Anti-T lymphocyte globulin (ATLG) was associated with a reduction of grade II-IV acute GVHD in comparison to ATG without increasing the incidence of relapse. This phase III randomised study propose to compare GVHD prevention with ATG versus ATLG in AML and MDS patients above 50 years of age transplanted with a matched unrelated donor following a fludarabine-treosulfan RIC, with the hypothesis that ATLG would better control GVHD in this population of patients thus limiting the risk of morbidity and mortality of the procedure.
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Etablissements

Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données
CLCC INSTITUT GUSTAVE ROUSSY PEFFAULT DE LA TOUR Regis En recrutement IDF 27/12/2025 07:46:28  Contacter
AP-HP Assistance publique - Hôpitaux de Paris En recrutement IDF 27/12/2025 07:46:28  Contacter
AP-HP - Hôpital Henri Mondor-Albert Chenevier
AP-HP - Hôpital La Pitié-Salpêtrière
AP-HP - Hôpital Necker-Enfants Malades
AP-HP - Hôpital Saint Antoine
AP-HP - Hôpital Saint Louis
Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données
AP-HP - Hôpital Necker-Enfants Malades Ambroise Marcais Contact (sur clinicalTrials)
AP-HP - Hôpital Saint Antoine Florent Malard Contact (sur clinicalTrials)
INSTITUT GUSTAVE ROUSSY Tereza Coman Contact (sur clinicalTrials)
Les établissements hors Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données
CHU Besançon - Besançon - France Etienne Daguindau Contact (sur clinicalTrials)
CHU Montpellier - Montpellier - France Patrice Ceballos Contact (sur clinicalTrials)
CHU Poitiers - Poitiers - France Natacha Maillard Contact (sur clinicalTrials)
CHU Rennes - Rennes - France Marc Bernard Contact (sur clinicalTrials)
Oncopole Toulouse - Toulouse - France Anne Huynh Contact (sur clinicalTrials)
Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données
CHRU Nancy - Nancy - France Marie-Thérèse Rubio Contact (sur clinicalTrials)
CHRU Strasbourg - Strasbourg - France Bruno Lioure Contact (sur clinicalTrials)
CHRU Tours - Tours - France Alban Villate Contact (sur clinicalTrials)
CHU Amiens - Amiens - France Amandine Charbonnier Contact (sur clinicalTrials)
CHU Angers - Angers - France Sylvie François Contact (sur clinicalTrials)
CHU Bordeaux - Bordeaux - France Edouard Forcade Contact (sur clinicalTrials)
CHU Brest - Brest - France Laura Herbreteau Contact (sur clinicalTrials)
CHU Caen - Caen - France Sylvain Chantepie Contact (sur clinicalTrials)
CHU Clermont-Ferrand - Clermont-Ferrand - France Aurélie Ravinet Contact (sur clinicalTrials)
CHU Grenoble - Grenoble - France Claude-Eric Bulabois Contact (sur clinicalTrials)
CHU Lille - Lille - France Valérie Coiteux Contact (sur clinicalTrials)
CHU Limoges - Limoges - France Pedro Henrique Delima Prata Contact (sur clinicalTrials)
CHU Lyon Sud - Lyon - France Sandrine Loron Contact (sur clinicalTrials)
CHU Nantes - Nantes - France Patrice Chevallier Contact (sur clinicalTrials)
CHU Nice - Nice - France Michael Loschi Contact (sur clinicalTrials)
CHU Saint Etienne - Saint-Etienne - France Jérôme Cornillon Contact (sur clinicalTrials)
Hôpital Henri Mondor AP-HP - Créteil - France Mathieu Leclerc Contact (sur clinicalTrials)
Hôpital La Pitié Salpêtrière AP-HP - Paris - France Stéphanie Nguyen-Quoc Contact (sur clinicalTrials)
Hôpital Saint Louis AP-HP - Paris - France Régis Peffault de Latour Contact (sur clinicalTrials)
IPC Marseille - Marseille - France Raynier Devillier Contact (sur clinicalTrials)

Critères

Tous


1. Age ≥ 50 and ≤ 70 years

2. Patient between 50 and 55 years should be unfit for a myeloblative conditioning
(SORROR score ≥2)

3. AML requiring allogeneic stem cell transplantation (intermediate or high-risk AML)
in complete cytologic response (CR1 or above) or MDS requiring allogeneic stem cell
transplantation (IPSS≥ 1.5 or IPSS-R > 4.5 or IPSS-R > 3-4.5 with risk features
[rapide blast increase, life-threatening neutropenia (<0.3 G/L) or thrombopenia
(<30G/L) or high transfusion needs (>2/month for 6 months)]

4. Without an HLA matched related donor

5. Having an identified matched HLA 10/10 unrelated donor

6. With usual criteria for HSCT:

1. ECOG performans status ≤ 2

2. No severe and uncontrolled infection

3. Cardiac left ventricular ejection fraction ≥50%

4. Lung DLCO > 40%

5. Adequate organ function: ASAT and ALAT ≤ 3N, total bilirubin ≤ 2N, creatinine
clearance ≥ 50 mL/min (except if those abnormalities are linked to the
hematological disease)

7. With health insurance coverage

8. Having signed a written informed consent

9. Contraception methods must be prescribed during all the duration of the research

NB: The authorized contraceptive methods are:

- For women of childbearing age and in absence of permanent sterilization: oral,
intravaginal or transdermal combined hormonal contraception, oral, injectable or
transdermal progestogen-only hormonal contraception, intrauterine hormonal releasing
system (IUS), sexual abstinence (only if this the preferred and usual lifestyle of
the participants).

- For man in absence of permanent sterilization: sexual abstinence, condoms

Exclusion Criteria:


1. Cancer in the last 5 years (except basal cell carcinoma of the skin or "in situ"
carcinoma of the cervix)

2. Uncontrolled infection

3. Seropositivity for HIV or HTLV-1 or active hepatitis B or C

4. Yellow fever vaccine and all others live virus vaccines within 2 months before
transplantation

5. Heart failure according to NYHA (II or more) or Left ventricular ejection fraction <
50%.

6. Lung DLCO ≤ 40%

7. Preexisting acute hemorrhagic cystitis

8. Renal failure with creatinine clearance < 50ml / min

9. Pregnancy (β-HCG positive) or breast-feeding

10. Patients with any debilitating medical or psychiatric illness, which would preclude
the realization of the SCT or the understanding of the protocol

11. Patient under state medical aid

12. Patient under legal protection (protection of the court, or in curatorship or
guardianship).

13. For Grafalon: Hypersensitivity to the active substance or to any of the excipients

14. For Thymoglobulin: Hypersensitivity to rabbit proteins or to any of the excipients

15. Participation in other interventional clinical trials

16. Any contraindication mentioned in the SmPC of all auxiliary medicinal products
planned to be used in the trial: cyclosporine, mycophenolate mofetil, fludarabine,
treosulfan