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
OPTISAGE
1 other identifier
interventional
324
1 country
28
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Nov 2023
Longer than P75 for phase_3
28 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 9, 2023
CompletedFirst Posted
Study publicly available on registry
October 13, 2023
CompletedStudy Start
First participant enrolled
November 28, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 28, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
November 28, 2028
April 27, 2026
April 1, 2026
5 years
October 9, 2023
April 22, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Incidence of grade II-IV acute Graft Versus Host Disease (GVHD) according to the Mount Sinai Acute GVHD International Consortium (MAGIC) classification
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.
At day 100 post-transplantation
Secondary Outcomes (39)
Number of patients with at least 3 consecutive days with neutrophils > 0.5 G/L and platelets > 20 G/L
Up to 24 months
T, B, NK, regulatory T cell and gammaglobulin levels in the peripheral blood
1 month after transplantation
T, B, NK, regulatory T cell and gammaglobulin levels in the peripheral blood
100 days after transplantation
T, B, NK, regulatory T cell and gammaglobulin levels in the peripheral blood
6 months after transplantation
T, B, NK, regulatory T cell and gammaglobulin levels in the peripheral blood
12 months after transplantation
- +34 more secondary outcomes
Study Arms (2)
Anti-T lymphocyte globulin (ATLG)
ACTIVE COMPARATORAnti Thymocyte Globulins (ATG)
ACTIVE COMPARATORInterventions
10 mg/Kg/day IV for 3 consecutive days (day-3 to -1 before transplantation)
2.5 mg/Kg/day IV for 2 consecutive days (day-3 and -2 before transplantation)
Eligibility Criteria
You may qualify if:
- 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:
- +2 more criteria
You may not qualify if:
- 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
- Yellow fever vaccine and all others live virus vaccines within 2 months before transplantation
- Heart failure according to NYHA (II or more) or Left ventricular ejection fraction \< 50%.
- Lung DLCO ≤ 40%
- Preexisting acute hemorrhagic cystitis
- Renal failure with creatinine clearance \< 50ml / min
- Pregnancy (β-HCG positive) or breast-feeding
- Patients with any debilitating medical or psychiatric illness, which would preclude the realization of the SCT or the understanding of the protocol
- Patient under state medical aid
- Patient under legal protection (protection of the court, or in curatorship or guardianship).
- 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
- Participation in other interventional clinical trials
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (28)
CHU Amiens
Amiens, France
CHU Angers
Angers, France
CHU Besançon
Besançon, France
CHU Bordeaux
Bordeaux, France
CHU Brest
Brest, France
CHU Caen
Caen, France
CHU Clermont-Ferrand
Clermont-Ferrand, France
Hôpital Henri Mondor AP-HP
Créteil, France
CHU Grenoble
Grenoble, France
CHU Lille
Lille, France
CHU Limoges
Limoges, France
CHU Lyon Sud
Lyon, France
IPC Marseille
Marseille, France
CHU Montpellier
Montpellier, France
CHRU Nancy
Nancy, France
CHU Nantes
Nantes, France
CHU Nice
Nice, France
Hôpital La Pitié Salpêtrière AP-HP
Paris, France
Hôpital Necker AP-HP
Paris, France
Hôpital Saint Louis AP-HP
Paris, France
Hôpital Saint-Antoine AP-HP
Paris, France
CHU Poitiers
Poitiers, France
CHU Rennes
Rennes, France
CHU Saint Etienne
Saint-Etienne, France
CHRU Strasbourg
Strasbourg, France
Oncopole Toulouse
Toulouse, France
CHRU Tours
Tours, France
Institut Gustave Roussy
Villejuif, France
MeSH Terms
Interventions
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 9, 2023
First Posted
October 13, 2023
Study Start
November 28, 2023
Primary Completion (Estimated)
November 28, 2028
Study Completion (Estimated)
November 28, 2028
Last Updated
April 27, 2026
Record last verified: 2026-04