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

NCT ID: NCT04857645

Last Updated: 2025-05-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 57 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-22
• Study Completion Date: 2025-04-22

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

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

Conditions

MDS; AML

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ASTX727 treatment

Group Type: EXPERIMENTAL

ASTX727

Intervention Type: DRUG

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

Donor Lymphocyte Infusions

Intervention Type: 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

Interventions

ASTX727

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

Intervention Type: DRUG

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

Intervention Type: OTHER

Other Intervention Names

DLI

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Astex Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: collaborator

Groupe Francophone des Myelodysplasies

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marie ROBIN, MD

Role: PRINCIPAL_INVESTIGATOR

Hôpital Saint Louis - Service hématologie-greffe

Pierre FENAUX, MD

Role: PRINCIPAL_INVESTIGATOR

Hôpital Saint Louis - Service hématologie séniors

Locations

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

Amiens, , France

CHU d'Angers - Service des maladies du sang

Angers, , France

CHU Estaing - Service hématologie clinique et thérapie cellulaire

Clermont-Ferrand, , France

CHU de Grenoble - Clinique Universitaire d'hématologie

Grenoble, , France

Hôpital Saint Eloi - Service hématologie clinique

Montpellier, , France

CHU Hôtel Dieu - Service hématologie clinique

Nantes, , France

Hôpital Saint Louis - Service hématologie-greffe

Paris, , France

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

Pessac, , France

CH Lyon Sud - Servide Hématologie

Pierre-Bénite, , France

Centre Henri Becquerel - Département d'hématologie

Rouen, , France

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

Toulouse, , France

CHU Brabois - Service hématologie clinique

Vandœuvre-lès-Nancy, , France

Countries

France

References

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.

Reference Type: DERIVED

PMID: 40784355 (View on PubMed)

Other Identifiers

GFM-DACORAL-DLI

Identifier Type: -

Identifier Source: org_study_id