Randomised Study of Oral Azacitidine vs Placebo Maintenance in AML or MDS Patients After Allo-SCT

Inclusion Criteria

• •1. Age ≥ 16 at the time of signing the informed consent form
• •2. Patients with a diagnosis of any of the below:
• •* AML (CR1 or CR2) according to World Health Organization (WHO) classification;
• •* Secondary AML (defined as previous history of MDS, antecedent hematological disease or chemotherapy exposure; CR1 or CR2); or
• •* Advanced or high risk MDS with an IPSS-R of ≥3.5 (intermediate 3.5 or higher) including intermediate or high risk chronic myelomonocytic leukaemia (CMML) (e.g. CPSS int-2 or high risk) (as per IPSS-R)
• •undergoing allo-SCT using myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC) preparative regimens, and with either peripheral blood or bone marrow as the source of hematopoietic stem cells.
• •3. At the time of allo-SCT
• •* No prior allo-SCT; and
• •* No more than 1 antigen mismatch at HLA-A, -B, -C, -DRB1 or -DQB1 locus for either related or unrelated donor; and
• •* No haplotype or cord blood donor; and
• •* Bone marrow blast \<5% for AML and \<10% for MDS patients
• •4. Able to commence therapy between 42 to 84 days following allo-SCT
• •5. Post-transplant bone marrow
• •1. AML patients - blast count ≤ 5% confirmed within 28 days prior to starting study therapy
• •2. MDS patients - confirmation of CR post-transplant with blast count ≤ 5% in bone marrow
• •6. Adequate neutrophil and platelet engraftment within 14 days prior to starting study therapy defined as:
• •* Absolute neutrophil count (ANC) ≥ 1.0 x 10\^9/L on two consecutive testing without daily use of myeloid growth factor; and
• •* Platelet ≥ 50 x 10\^9/L on two consecutive testing without platelet transfusion within 1 week
• •7. Adequate organ function:
• •* Serum aspartate aminotransferase (AST) and alanine transaminase (ALT) \< 4 x upper limit of normal (ULN)
• •* Serum bilirubin \< 2 x ULN. Higher levels are acceptable if these can be attributed to active red blood cell (RBC) precursor destruction within the bone marrow (i.e., ineffective erythropoiesis) or Gilbert's syndrome
• •* Serum creatinine \< 2 x ULN
• •8. Adequate coagulation (Prothrombin time (PT) ≤ 15 seconds and partial thromboplastin time (PTT) ≤ 40 seconds)
• •9. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
• •10. Patients with adequately controlled GVHD (defined as GVHD grade \<II with concurrent use of corticosteroids equivalent of prednisone at a dose ≤ 0.5 mg/kg) can be included
• •11. Females of childbearing potential (FCBP) may participate, providing they meet the following conditions:
• •1. Agree to use at least two effective contraceptive methods (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomised partner) or practice true abstinence throughout the study, and for 6 months following the last dose of study therapy and
• •2. Have a negative serum pregnancy test (sensitivity of at least 25 mIU/mL) at screening; and
• •3. Have a negative serum or urine (investigator's discretion) pregnancy test (sensitivity of at least 25 mIU/mL) within 72 hours prior to starting study therapy. This applies even if the subject practices complete abstinence from heterosexual contact.
• •12. Male patients with a female partner of childbearing potential must agree to the use of at least two physician-approved contraceptive methods throughout the course of the study and should avoid fathering a child during the course of the study and for 3 months following the last dose study therapy
• •13. Understand and voluntarily sign an informed consent from prior to any study related assessments or procedures being conducted
• •14. Able to adhere to the study visit schedule (i.e., clinic visits at the study sites are mandatory, unless noted otherwise for study visits) and other protocol requirements