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

AML Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04857645
• Other study ID #: GFM-DACORAL-DLI
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 22, 2021
• Est. completion date: April 2025

Study information

• Verified date: April 2024
• Source: Groupe Francophone des Myelodysplasies
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 57
• Est. completion date: April 2025
• Est. primary completion date: April 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• AML
• MDS

Intervention

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

Locations

Country	Name	City	State
France	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

Sponsors (2)

Lead Sponsor	Collaborator
Groupe Francophone des Myelodysplasies	Astex Pharmaceuticals, Inc.

Country where clinical trial is conducted

France, 

Outcome

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