Clinical trial NCT04857645: ASTX727 and Donor Lymphocyte Infusions After Allogenic Stem Cell Transplantation in Very High Risk MDS or AML Patients
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: MDS
AML
Keywords: Very high risk MDS
AML
ASTX727
DLI
Lead sponsor: Groupe Francophone des Myelodysplasies
Sponsor class: OTHER
Collaborators: name: Astex Pharmaceuticals, Inc.
First posted: 2021-04-23
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: Disease free Survival (DFS) at one year post transplant
timeFrame: 1 year post transplant
Secondary outcomes:
measure: Overall Survival (OS) at one year post transplant
timeFrame: 1 year post transplant
measure: Overall Survival (OS) at two years post transplant
timeFrame: 2 years post transplant
measure: Risk factors for DFS, OS and non-relapse mortality at 1 and 2 years
timeFrame: 1 and 2 years
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU d'Amiens Picardie - Site sud - Service hématologie clinique et thérapie cellulaire
city: Angers
country: France
facility: CHU d'Angers - Service des maladies du sang
city: Clermont-Ferrand
country: France
facility: CHU Estaing - Service hématologie clinique et thérapie cellulaire
city: Grenoble
country: France
facility: CHU de Grenoble - Clinique Universitaire d'hématologie
city: Montpellier
country: France
facility: Hôpital Saint Eloi - Service hématologie clinique
city: Nantes
country: France
facility: CHU Hôtel Dieu - Service hématologie clinique
city: Paris
country: France
facility: Hôpital Saint Louis - Service hématologie-greffe
city: Pessac
country: France
facility: CHU de Haut-Lévèque de Bordeaux - Service des maladies du sang
city: Pierre-Bénite
country: France
facility: CH Lyon Sud - Servide Hématologie
city: Rouen
country: France
facility: Centre Henri Becquerel - Département d'hématologie
city: Toulouse
country: France
facility: IUCT Oncopole - Département d'hématologie - Service de greffe de cellules souches hématopoïétiques
city: Vandœuvre-lès-Nancy
country: France
facility: CHU Brabois - Service hématologie clinique
Study officials:
affiliation: Hôpital Saint Louis - Service hématologie-greffe
name: Marie ROBIN, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpital Saint Louis - Service hématologie séniors
name: Pierre FENAUX, MD
role: PRINCIPAL_INVESTIGATOR
References: