ASTX727 AND DONOR LYMPHOCYTE INFUSIONS AFTER ALLOGENEIC STEM CELL TRANSPLANTATION IN VERY HIGH RISK MDS OR AML PATIENTS

Other illness

• 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 EF < 50%

Lab values

• Proliferative disease in patients not in remission: 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

Other

• ECOG 3 or more
• No contraception
• Pregnant or breastfeeding women
• Creatininemia level > 150 µmol/L
• Liver enzyme > 3 N
• Conjugated bilirubinemia > 25 µmol/L
• MDS occurring in patients with Fanconi anemia or congenital dyskeratosis

• Patients aged from 18 to 70 years
• MDS, CMML or AML should have at least one of those criteria: 1) For MDS: Revised IPSS poor or very poor ; For AML: ELN adverse risk ; 2) 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 ; 3) AML post MDS or MPN, or AML relapsing less than 2 years after first CR
• AML patients should have received chemotherapy
• Marrow blast < 20% for MDS and < 10% for AML post chemotherapy before HSCT
• 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 3 months after the last dose of study drug therapy.