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

A Phase II Prospective Study "GFM-DACORAL-DLI" ASTX727 and Donor Lymphocyte Infusions After Allogenic Stem Cell Transplantation in Very High Risk MDS or AML Patients

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

Study Overview

• Status: Completed
• Conditions: AML; MDS
• Intervention / Treatment: Drug: ASTX727; Other: Donor Lymphocyte Infusions

Detailed Description

Prospective 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

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Amiens, France, 80054
    • CHU d'Amiens Picardie - Site sud - Service hématologie clinique et thérapie cellulaire
  • Angers, France, 49933
    • CHU D'ANGERS - Service des Maladies du Sang
  • Clermont-Ferrand, France, 63000
    • CHU Estaing - Service hématologie clinique et thérapie cellulaire
  • Grenoble, France, 38043
    • CHU de Grenoble - Clinique Universitaire d'hématologie
  • Montpellier, France, 34295
    • Hôpital Saint Eloi - Service hématologie clinique
  • Nantes, France, 44093
    • CHU Hôtel Dieu - Service hématologie clinique
  • Paris, France, 75010
    • Hôpital Saint Louis - Service hématologie-greffe
  • Pessac, France, 33604
    • CHU de Haut-Lévèque de Bordeaux - Service des maladies du sang
  • Pierre-Bénite, France, 69645
    • CH Lyon Sud - Servide Hématologie
  • Rouen, France, 76038
    • Centre Henri Becquerel - Département d'hématologie
  • Toulouse, France, 31059
    • IUCT Oncopole - Département d'hématologie - Service de greffe de cellules souches hématopoïétiques
  • Vandœuvre-lès-Nancy, France, 54511
    • CHU Brabois - Service hématologie clinique

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients aged from 18 to 70 years
• MDS or AML with unfavorable genetics defined as follow:
• 4 or more cytogenetic abnormalities or
• 3 cytogenetic abnormalities and TP53 or other unfavorable mutations (ASXL1, RUNX1) or
• 3 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.

Exclusion Criteria:

• ECOG 3 or more
• Cancer less than 2 years before inclusion or cancer not in remission the last 2 years before inclusion (except in situ cancer or baso cellular cancer)
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ASTX727 treatment	Drug: ASTX727; Eligible patient started ASTX727 between 40 and 130 days after allogenic stem cell transplantation; Other: Donor Lymphocyte Infusions; 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; Other Names: DLI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS) at one year post transplant	Measure of time from randomization to death from any cause	1 year post transplant
Overall Survival (OS) at two years post transplant	Measure of time from randomization to death from any cause	2 years post transplant
Risk factors for DFS, OS and non-relapse mortality at 1 and 2 years	Statistical study of cumulative incidence curves	1 and 2 years

Collaborators and Investigators

• Sponsor: Groupe Francophone des Myelodysplasies
• Collaborators: Astex Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Marie ROBIN, MD, Hôpital Saint Louis - Service hématologie-greffe; Principal Investigator: Pierre FENAUX, MD, Hôpital Saint Louis - Service hématologie séniors

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2021
• Primary Completion (Actual): April 30, 2024
• Study Completion (Actual): April 22, 2025

Study Registration Dates

• First Submitted: April 19, 2021
• First Submitted That Met QC Criteria: April 22, 2021
• First Posted (Actual): April 23, 2021

Study Record Updates

• Last Update Posted (Actual): May 14, 2025
• Last Update Submitted That Met QC Criteria: May 9, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: AML; DLI; ASTX727; Very high risk MDS
• Additional Relevant MeSH Terms: Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Decitabine and cedazuridine drug combination
• Other Study ID Numbers: GFM-DACORAL-DLI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No