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GVHDPhase 3OPTISAGENCT06083129

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

A Phase 3 study testing Grafalon and Thymoglobulin in people with GVHD, run by Assistance Publique - Hôpitaux de Paris at 28 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

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. Read more about this study

Who is it for?
Ages 50 to 70 years
Conditions the study is for
GVHD
What is being tested?
Grafalon and Thymoglobulin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
324 participants
Where
28 sitesFrance
Study dates
28 Nov 2023to 28 Nov 2028
Phase
Phase 3
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 50 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
Show all 17Show fewer
  • 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

Who cannot join

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

Trial locations and contacts

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

Régis Peffault de Latour, Pr contact

+33142385073

regis.peffaultdelatour@aphp.fr

Jérôme Lambert, Dr contact

+33142499742

jerome.lambert@u-paris.fr

28 sites in 1 country

France28 sites, 28 recruiting

  • CHU Amiens

    Amiens

    Amandine Charbonnier, +33322455916 ext. +33, Charbonnier.Amandine@chu-amiens.fr

    Recruiting

  • CHU Angers

    Angers

    Sylvie François, +33241354472 ext. +33, SyFrancois@chu-angers.fr

    Recruiting

  • CHU Besançon

    Besançon

    Etienne Daguindau, +33381668351 ext. +33, edaguindau@chu-besancon.fr

    Recruiting

  • CHU Bordeaux

    Bordeaux

    Edouard Forcade, +33557656511 ext. +33, edouard.forcade@chu-bordeaux.fr

    Recruiting

  • CHU Brest

    Brest

    Laura Herbreteau, +33298223395 ext. +33, laura.herbreteau@chu-brest.fr

    Recruiting

  • CHU Caen

    Caen

    Sylvain Chantepie, +33231272073 ext. +33, Chantepie-s@chu-caen.fr

    Recruiting

  • CHU Clermont-Ferrand

    Clermont-Ferrand

    Aurélie Ravinet, +33473750074 ext. +33, aravinet@chu-clermontferrand.fr

    Recruiting

  • Hôpital Henri Mondor AP-HP

    Créteil

    Mathieu Leclerc, +33149812057 ext. +33, Mathieu.leclerc@aphp.fr

    Not yet recruiting

  • CHU Grenoble

    Grenoble

    Claude-Eric Bulabois, +33241354472 ext. +33, CEBulabois@chu-grenoble.fr

    Recruiting

  • CHU Lille

    Lille

    Valérie Coiteux, +33320455551 ext. +33, Valerie.COITEUX@chru-lille.fr

    Recruiting

  • CHU Limoges

    Limoges

    Pedro Henrique Delima Prata, +33555058039 ext. +33, Pedro.prata@chu-limoges.fr

    Recruiting

  • CHU Lyon Sud

    Lyon

    Sandrine Loron, +33478862240 ext. +33, sandrine.loron@chu-lyon.fr

    Recruiting

  • IPC Marseille

    Marseille

    Raynier Devillier, +33491223754 ext. +33, DEVILLIERR@ipc.unicancer.fr

    Recruiting

  • CHU Montpellier

    Montpellier

    Patrice Ceballos, +33467338079 ext. +33, p-ceballos@chu-montpellier.fr

    Recruiting

  • CHRU Nancy

    Nancy

    Marie-Thérèse Rubio, +33385153262 ext. +33, m.rubio@chru-nancy.fr

    Recruiting

  • CHU Nantes

    Nantes

    Patrice Chevallier, +33240083271 ext. +33, patrice.chevallier@chu-nantes.fr

    Recruiting

  • CHU Nice

    Nice

    Michael Loschi, +33492035558 ext. +33, loschi.m@chu-nice.fr

    Recruiting

  • Hôpital La Pitié Salpêtrière AP-HP

    Paris

    Stéphanie Nguyen-Quoc, +33142162823 ext. +33, stephanie.nguyen-quoc@aphp.fr

    Recruiting

  • Hôpital Necker AP-HP

    Paris

    Ambroise Marcais, +33144494699 ext. +33, ambroise.marcais@aphp.fr

    Recruiting

  • Hôpital Saint Louis AP-HP

    Paris

    Régis Peffault de Latour, +33142499639 ext. +33, regis.peffaultdelatour@aphp.fr

    Recruiting

  • Hôpital Saint-Antoine AP-HP

    Paris

    Florent Malard, +33171970292 ext. +33, Florent.malard@inserm.fr

    Recruiting

  • CHU Poitiers

    Poitiers

    Natacha Maillard, +33549444307 ext. +33, natacha.maillard@chu-poitiers.fr

    Recruiting

  • CHU Rennes

    Rennes

    Marc Bernard, +33299284161 ext. +33, marc.bernard@chu-rennes.fr

    Recruiting

  • CHU Saint Etienne

    Saint-Etienne

    Jérôme Cornillon, +33477917060 ext. +33, Jerome.cornillon@icloire.fr

    Recruiting

  • CHRU Strasbourg

    Strasbourg

    Bruno Lioure, +33368767403 ext. +33, b.lioure@icans.eu

    Recruiting

  • Oncopole Toulouse

    Toulouse

    Anne Huynh, +33531156189 ext. +33, huynh.anne@iuct-oncopole.fr

    Recruiting

  • CHRU Tours

    Tours

    Alban Villate, +33247473712 ext. +33, a.villate@chu-tours.fr

    Not yet recruiting

  • Institut Gustave Roussy

    Villejuif

    Tereza Coman, +33142115008 ext. +33, Tereza.COMAN@gustaveroussy.fr

    Recruiting

Other trials in France

About this study

Official title: 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

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.

Conditions
GVHD
Being tested
Grafalon, Thymoglobulin

What participants receive

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

  • GrafalonDrug

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

  • ThymoglobulinDrug

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

Study groups in NCT06083129
Study groupRoleWhat they receive
Anti-T lymphocyte globulin (ATLG)Active comparatorNot described
Receives: Drug: Grafalon
Anti Thymocyte Globulins (ATG)Active comparatorNot described
Receives: Drug: Thymoglobulin

What is being measured

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

  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.

    Measured: At day 100 post-transplantation

Secondary outcomes (39)

  1. Number of patients with at least 3 consecutive days with neutrophils > 0.5 G/L and platelets > 20 G/L

    Hematopoietic recoveries

    Measured: Up to 24 months

  2. T, B, NK, regulatory T cell and gammaglobulin levels in the peripheral blood

    Immune reconstitution

    Measured: 1 month after transplantation

  3. T, B, NK, regulatory T cell and gammaglobulin levels in the peripheral blood

    Immune reconstitution

    Measured: 100 days after transplantation

  4. T, B, NK, regulatory T cell and gammaglobulin levels in the peripheral blood

    Immune reconstitution

    Measured: 6 months after transplantation

  5. T, B, NK, regulatory T cell and gammaglobulin levels in the peripheral blood

    Immune reconstitution

    Measured: 12 months after transplantation

  6. T, B, NK, regulatory T cell and gammaglobulin levels in the peripheral blood

    Immune reconstitution

    Measured: 24 months after transplantation

  7. Percentage of chimerism

    Measured: 1 month after transplantation

  8. Percentage of chimerism

    Measured: 100 days after transplantation

  9. Percentage of chimerism

    Measured: 6 months after transplantation

  10. Percentage of chimerism

    Measured: 12 months after transplantation

  11. Incidence of grade I acute GVHD

    Treatments for acute GVHD will be described : first line treatment, response to steroids, treatment courses for refractory acute GVHD

    Measured: Up to 24 months

  12. Incidence of chronic GVHD

    Incidence of chronic GVHD according to National Institutes of Health (NIH) classification. The gradation of chronic GvHD is defined by the number and score of affected organ. The higher the score of each organ and the higher the number of organs affected, the more severe the damage.

    Measured: 12 months after transplantation

  13. Incidence of chronic GVHD

    Incidence of chronic GVHD according to National Institutes of Health (NIH) classification. The gradation of chronic GvHD is defined by the number and score of affected organ. The higher the score of each organ and the higher the number of organs affected, the more severe the damage.

    Measured: 24 months after transplantation

  14. Incidence of relapse

    Relapse will be defined by the reappearance of leukemic cells or MDS features after allo-HSCT in the bonne marrow (cytology +/- cytogenetic analysis from bone marrow aspiration) or extra-medullary sites (proven by a biopsy).

    Measured: 12 months after transplantation

  15. Incidence of relapse

    Relapse will be defined by the reappearance of leukemic cells or MDS features after allo-HSCT in the bonne marrow (cytology +/- cytogenetic analysis from bone marrow aspiration) or extra-medullary sites (proven by a biopsy).

    Measured: 24 months after transplantation

  16. Progression free survival

    Measured: 12 months after transplantation

  17. Progression free survival

    Measured: 24 months after transplantation

  18. Number of severe infections

    Severe infections correspond to grade 3-4 according to Common Terminology Criteria for Adverse Events

    Measured: 100 days after transplantation

  19. Number of severe infections

    Severe infections correspond to grade 3-4 according to Common Terminology Criteria for Adverse Events

    Measured: 12 months after transplantation

  20. Incidence of CytoMegaloVirus (CMV) reactivation

    Measured: 100 days after transplantation

  21. Incidence of CytoMegaloVirus (CMV) reactivation

    Measured: 6 months after transplantation

  22. Incidence of CytoMegaloVirus (CMV) reactivation

    Measured: 12 months after transplantation

  23. Incidence of Ebstein Barr Virus (EBV) reactivation

    Measured: 100 days after transplantation

  24. Incidence of Ebstein Barr Virus (EBV) reactivation

    Measured: 6 months after transplantation

  25. Incidence of Ebstein Barr Virus (EBV) reactivation

    Measured: 12 months after transplantation

  26. Non-relapse mortality

    Measured: 6 months after transplantation

  27. Non-relapse mortality

    Measured: 12 months after transplantation

  28. Non-relapse mortality

    Measured: 24 months after transplantation

  29. Overall survival

    Measured: 12 months after transplantation

  30. Overall survival

    Measured: 24 months after transplantation

  31. GVHD and relapse free survival (GRFS)

    Defined by being alive without disease relapse and without having developed acute grade III-IV or severe chronic GVHD

    Measured: Up to 24 months after transplantation

  32. Health-related Quality of life

    Assessed by using the FACT-BMT-v4 questionnaire. It is a 50 items score. The score varies between 0 to 200. The higher the score the lower the quality of life.

    Measured: At inclusion

  33. Health-related Quality of life

    Assessed by using the FACT-BMT-v4 questionnaire. It is a 50 items score. The score varies between 0 to 200. The higher the score the lower the quality of life.

    Measured: 100 days after transplantation

  34. Health-related Quality of life

    Assessed by using the FACT-BMT-v4 questionnaire. It is a 50 items score. The score varies between 0 to 200. The higher the score the lower the quality of life.

    Measured: 6 months after transplantation

  35. Health-related Quality of life

    Assessed by using the FACT-BMT-v4 questionnaire. It is a 50 items score. The score varies between 0 to 200. The higher the score the lower the quality of life.

    Measured: 12 months after transplantation

  36. Number of days of hospitalization for the transplant and after the hospitalization for transplantation related complications

    Measured: Up to 12 months after transplantation

  37. Incidence and severity of veino-occlusive disease (VOD)

    Measured: 100 days after transplantation

  38. Lymphocyte counts on standard blood counts before conditioning

    Measured: 7 days before transplantation

  39. Number of late acute GvHD, overlap syndromes and chronic GvHD

    Measured: from day 100 to day 120 after transplantation

Timeline

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

  1. First posted13 Oct 2023
  2. Study start28 Nov 2023
  3. Primary completion28 Nov 2028 (estimated)
  4. Study completion28 Nov 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 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
324 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06083129
Sponsor's protocol ID
APHP230276
Acronym
OPTISAGE
Status last verified
Apr 2026
First submitted
9 Oct 2023
Last updated
27 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Grafalon and Thymoglobulin in people with GVHD, run by Assistance Publique - Hôpitaux de Paris at 28 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 17 inclusion and 16 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 27 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 28 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 Régis Peffault de Latour, Pr (+33142385073, regis.peffaultdelatour@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of grade II-IV acute Graft Versus Host Disease (GVHD) according to the Mount Sinai Acute GVHD International Consortium (MAGIC) classification (time frame: At day 100 post-transplantation). 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 NCT06083129.

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 27 Apr 2026.

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