NCT06083129RecruitingPhase 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
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
Source: ClinicalTrials.gov · Last updated 27 Apr 2026
Brief summary (registry, in English)
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.
- Status (registry)
- Recruiting
- Phase (registry)
- Phase 3
- Study type
- Interventional
- Enrollment
- 324 (estimated)
- First submitted
- 9 Oct 2023
- Start date
- Nov 2023
- Primary completion date
- Nov 2028
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Diseases
- Acute myeloid leukemia
- NCT number
- NCT06083129
What you commit to
- Study type: Interventional · Phase 3
- Planned participants: 324
- From Nov 2023 to the primary completion date, Nov 2028
- 28 sites in 1 country
- Visits and tests: ask the trial team, the registry does not list them
Built from the registry fields of ClinicalTrials.gov. It describes the study, not your situation.
Who cannot take part
Copied verbatim from ClinicalTrials.gov and grouped by topic. Only the trial team decides who can take part.
Prior treatment
- Yellow fever vaccine and all others live virus vaccines within 2 months before transplantation
Other illness
- Cancer in the last 5 years (except basal cell carcinoma of the skin or "in situ" carcinoma of the cervix)
- Uncontrolled infection
- Seropositivity for HIV or HTLV-1 or active hepatitis B or C
- Patients with any debilitating medical or psychiatric illness, which would preclude the realization of the SCT or the understanding of the protocol
- For Grafalon: Hypersensitivity to the active substance or to any of the excipients
- For Thymoglobulin: Hypersensitivity to rabbit proteins or to any of the excipients
Lab values
- Heart failure according to NYHA (II or more) or Left ventricular ejection fraction \< 50%.
- Renal failure with creatinine clearance \< 50ml / min
Other
- Lung DLCO ≤ 40%
- Preexisting acute hemorrhagic cystitis
- Pregnancy (β-HCG positive) or breast-feeding
- Patient under state medical aid
- Patient under legal protection (protection of the court, or in curatorship or guardianship).
- Participation in other interventional clinical trials
- Any contraindication mentioned in the SmPC of all auxiliary medicinal products planned to be used in the trial: cyclosporine, mycophenolate mofetil, fludarabine, treosulfan
Who the study is looking for
- Age ≥ 50 and ≤ 70 years
- Patient between 50 and 55 years should be unfit for a myeloblative conditioning (SORROR score ≥2)
- 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 \[rapide blast increase, life-threatening neutropenia (\<0.3 G/L) or thrombopenia (\<30G/L) or high transfusion needs (\>2/month for 6 months)\]
- Without an HLA matched related donor
- Having an identified matched HLA 10/10 unrelated donor
- With usual criteria for HSCT:
- ECOG performans status ≤ 2
- No severe and uncontrolled infection
- Cardiac left ventricular ejection fraction ≥50%
- Lung DLCO \> 40%
- 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)
- With health insurance coverage
- Having signed a written informed consent
- 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
Age in the registry: 50 years to 70 years · Sex: All · Does not accept healthy volunteers
Sites (28)
Sites in registry order. Pick your city on the disease page to sort them by distance.
This page is information, not medical advice. Discuss any trial with your doctor.