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

Study Overview
=================
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

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

Conditions
-----------------
MDS, AML

Intervention / Treatment
-----------------
* Drug: ASTX727
* Other: Donor Lymphocyte Infusions


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ASTX727 treatment<br> | Drug: ASTX727<br>* Eligible patient started ASTX727 between 40 and 130 days after allogenic stem cell transplantation<br>Other: Donor Lymphocyte Infusions<br>* 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<br>* 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Very high risk MDS, AML, ASTX727, DLI