Ireland
--:--IST
Latest
Astellas Expands Its 330 Million Euro Tralee Biopharma Facility with a Second Aseptic Filling Line to Double Drug-Product Capacity Xeolas Pharmaceuticals Opens 158,000 Sq Ft State-of-the-Art Baldoyle Facility to Scale Specialty Medicine Manufacturing Priya Life Science Partners with Fleming for the 9th Annual Corporate Compliance & Transparency in Life Sciences Summit in Zurich Ireland Has the Capital and the Lessons: Digital Project Management Is How They Become Delivery Dunbar Pharma Brings First Plant-Derived Dronabinol API to UK Market Through IPS Pharma Leveraging Priya Life Science as a Data Tracker: The Ultimate Use Case & Career Guide The €100K Reality Check: Why a Six-Figure Pharma Salary in Ireland Feels Different Than in Switzerland or Germany Ireland's €93.8 Billion Non-EU Pharma Export Engine: Trade Data, Destination Markets, and Economic Impact Astellas Expands Its 330 Million Euro Tralee Biopharma Facility with a Second Aseptic Filling Line to Double Drug-Product Capacity Xeolas Pharmaceuticals Opens 158,000 Sq Ft State-of-the-Art Baldoyle Facility to Scale Specialty Medicine Manufacturing Priya Life Science Partners with Fleming for the 9th Annual Corporate Compliance & Transparency in Life Sciences Summit in Zurich Ireland Has the Capital and the Lessons: Digital Project Management Is How They Become Delivery Dunbar Pharma Brings First Plant-Derived Dronabinol API to UK Market Through IPS Pharma Leveraging Priya Life Science as a Data Tracker: The Ultimate Use Case & Career Guide The €100K Reality Check: Why a Six-Figure Pharma Salary in Ireland Feels Different Than in Switzerland or Germany Ireland's €93.8 Billion Non-EU Pharma Export Engine: Trade Data, Destination Markets, and Economic Impact
Recruiting Phase 3

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

NCT06083129 · tracked via the Priya Life Science France tracker
Phase
Phase 3
Started
2023-11-28
Last updated
2026-04-27

Condition(s) studied

GVHD

Investigational drug(s) / intervention(s)

Grafalon →Thymoglobulin →

Grafalon: 10 mg/Kg/day IV for 3 consecutive days (day-3 to -1 before transplantation)

Thymoglobulin: 2.5 mg/Kg/day IV for 2 consecutive days (day-3 and -2 before transplantation)

Study summary

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.

Eligibility

Sex
ALL
Min age
50 Years
Max age
70 Years
Healthy volunteers
No
Inclusion Criteria: 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

Primary outcome measure(s)

  • Incidence of grade II-IV acute Graft Versus Host Disease (GVHD) according to the Mount Sinai Acute GVHD International Consortium (MAGIC) classification — At day 100 post-transplantation
    Acute GVHD MAGIC classification permit to diagnose and score the severity of acute GVHD. MAGIC score varies from Grade 0 to Grade 4. The higher the score the more severe the damage.

Trial sites (28)

FacilityCityRegionStatus
CHU Amiens Amiens France Recruiting
CHU Angers Angers France Recruiting
CHU Besançon Besançon France Recruiting
CHU Bordeaux Bordeaux France Recruiting
CHU Brest Brest France Recruiting
CHU Caen Caen France Recruiting
CHU Clermont-Ferrand Clermont-Ferrand France Recruiting
Hôpital Henri Mondor AP-HP Créteil France Not Yet Recruiting
CHU Grenoble Grenoble France Recruiting
CHU Lille Lille France Recruiting
CHU Limoges Limoges France Recruiting
CHU Lyon Sud Lyon France Recruiting
IPC Marseille Marseille France Recruiting
CHU Montpellier Montpellier France Recruiting
CHRU Nancy Nancy France Recruiting
CHU Nantes Nantes France Recruiting
CHU Nice Nice France Recruiting
Hôpital La Pitié Salpêtrière AP-HP Paris France Recruiting
Hôpital Necker AP-HP Paris France Recruiting
Hôpital Saint Louis AP-HP Paris France Recruiting
Hôpital Saint-Antoine AP-HP Paris France Recruiting
CHU Poitiers Poitiers France Recruiting
CHU Rennes Rennes France Recruiting
CHU Saint Etienne Saint-Etienne France Recruiting
CHRU Strasbourg Strasbourg France Recruiting
Oncopole Toulouse Toulouse France Recruiting
CHRU Tours Tours France Not Yet Recruiting
Institut Gustave Roussy Villejuif France Recruiting
Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT06083129 on ClinicalTrials.gov ↗ ← All trials in France