ASTX727 and Donor Lymphocyte Infusions After Allogenic Stem Cell Transplantation in Very High Risk MDS or AML Patients

NCT04857645 | Completed Phase 2 DMC

• 1 other identifier: GFM-DACORAL-DLI
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 12

Brief Summary

Study of early administration of ASTX727 associated with late Donor Lymphocyte Infusions after allogenic stem cell transplantation in very high risk MDS or AML patients

Conditions

MDS; AML

Keywords

Very high risk MDS; AML; ASTX727; DLI

Outcome Measures

Primary Outcomes (1)

• Disease free Survival (DFS) at one year post transplant

  Measure of time during which no sign of progression is found

  1 year post transplant

Secondary Outcomes (3)

• Overall Survival (OS) at one year post transplant

  1 year post transplant

• Overall Survival (OS) at two years post transplant

  2 years post transplant

• Risk factors for DFS, OS and non-relapse mortality at 1 and 2 years

  1 and 2 years

Study Arms (1)

ASTX727 treatment

EXPERIMENTAL

Drug: ASTX727; Other: Donor Lymphocyte Infusions

Interventions

ASTX727 DRUG

Eligible patient started ASTX727 between 40 and 130 days after allogenic stem cell transplantation

ASTX727 treatment

Donor Lymphocyte Infusions OTHER

In absence of previous grade 2-4 or chronic graft-versus-host disease (GVHD), DLI will be administered at increasing doses the first day of ASTX727 cycles

Also known as: DLI

ASTX727 treatment

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged from 18 to 70 years
• MDS or AML with unfavorable genetics defined as follow:
• or more cytogenetic abnormalities or
• cytogenetic abnormalities and TP53 or other unfavorable mutations (ASXL1, RUNX1) or
• cytogenetic abnormalities and monosomal karyotype or
• mutations involving EVI1
• AML patients should have received chemotherapy
• Marrow blast \< 20% for MDS and \< 10% for AML post chemotherapy
• For MDS : Revised IPSS poor or very poor ; For AML : ELN adverse risk
• Non-proliferative disease
• A donor is available (HLA matched or mismatched)
• Adequate contraception in women \< 50 years and for men. Subjects must agree to use, and to be able to comply with, effective contraception without interruption, at least the first six months after transplant, throughout the entire duration of study drug therapy and for at least 6 months for women and 3 months for men after the last dose of study drug therapy.

You may not qualify if:

• ECOG 3 or more
• Cardiac failure with Ejection Fraction \< 50%
• Creatininemia level \> 150 µmol/L
• Liver enzyme \> 3 N
• Conjugated bilirubinemia \> 25 µmol/L
• MDS occurring in patients with Fanconi anemia or congenital dyskeratosis
• Proliferative disease in patients not in remission: White Blood Cell (WBC) \> 15 G/L or use of continuous cytotoxic to maintain WBC \< 15 G/L
• AML with marrow or peripheral blast count higher than 10% after chemotherapy
• Known allergy or hypersensitivity to the investigational agent or decitabine or its metabolites or formulation excipients
• No contraception
• Pregnant or breastfeeding women

Sponsors & Collaborators

• Groupe Francophone des Myelodysplasies: lead
• Astex Pharmaceuticals, Inc.: collaborator

Study Sites (12)

CHU d'Amiens Picardie - Site sud - Service hématologie clinique et thérapie cellulaire

Amiens, 80054, France

Location

CHU d'Angers - Service des maladies du sang

Angers, 49933, France

Location

CHU Estaing - Service hématologie clinique et thérapie cellulaire

Clermont-Ferrand, 63000, France

Location

CHU de Grenoble - Clinique Universitaire d'hématologie

Grenoble, 38043, France

Location

Hôpital Saint Eloi - Service hématologie clinique

Montpellier, 34295, France

Location

CHU Hôtel Dieu - Service hématologie clinique

Nantes, 44093, France

Location

Hôpital Saint Louis - Service hématologie-greffe

Paris, 75010, France

Location

CHU de Haut-Lévèque de Bordeaux - Service des maladies du sang

Pessac, 33604, France

Location

CH Lyon Sud - Servide Hématologie

Pierre-Bénite, 69645, France

Location

Centre Henri Becquerel - Département d'hématologie

Rouen, 76038, France

Location

IUCT Oncopole - Département d'hématologie - Service de greffe de cellules souches hématopoïétiques

Toulouse, 31059, France

Location

CHU Brabois - Service hématologie clinique

Vandœuvre-lès-Nancy, 54511, France

Location

Related Publications (1)

• Robin M, D'Aveni M, Stamatoullas A, Raffoux E, Chevallier P, Garnier A, Mediavilla C, Carre M, Himberlin C, Sebert M, Ravinet A, Desseaux K, Labussiere H, Alani M, Rubio MT, Huynh A, Ades L, de Latour RP, Paul F, Chermat F, Petit R, Mokeddem C, Charbonnier A, Thepot S, Chevret S, Fenaux P; Societe Francophone de Greffe de Moelle et de Therapie Cellulaire (SFGM-TC) and the Groupe Francophone des Myelodysplasies (GFM). Oral decitabine and cedazuridine maintenance after haematopoietic stem-cell transplantation in very high-risk acute myeloid leukaemia or myelodysplastic syndrome (GFM-DACORAL-DLI): a multicentre, single-arm, phase 2 trial. Lancet Haematol. 2025 Sep;12(9):e705-e716. doi: 10.1016/S2352-3026(25)00172-3. Epub 2025 Aug 7.

  PMID: 40784355 DERIVED

MeSH Terms

Interventions

decitabine and cedazuridine drug combination

Study Officials

• Marie ROBIN, MD

  Hôpital Saint Louis - Service hématologie-greffe

  PRINCIPAL INVESTIGATOR

• Pierre FENAUX, MD

  Hôpital Saint Louis - Service hématologie séniors

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 19, 2021
• First Posted: April 23, 2021
• Study Start: June 22, 2021
• Primary Completion: April 30, 2024
• Study Completion: April 22, 2025
• Last Updated: May 14, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (12)