Combined Evaluation of Epigenetic and Sensitising Therapy in AML and MDS

Inclusion Criteria

• •Participants must meet all of the following criteria at the time of screening:
• •1. Age ≥ 18 years
• •2. Documented diagnosis of:
• •1. Myelodysplastic syndrome (MDS) classified as intermediate-2 or high risk according to the International Prognostic Scoring System (IPSS), or
• •2. Acute Myeloid Leukaemia (AML) with 20-30% marrow blasts and multilineage dysplasia, according to WHO classification, or
• •3. Chronic myelomonocytic leukemia (CMML) with 10-29% marrow blasts without myeloproliferative disorder according to World Health Organisation (WHO) classification. This confirmation will be from either the Bone marrow aspirate (BMA) performed at screening or a standard of care BMA if performed up to 6 weeks before cycle 1 day 1.
• •3. Performance status by Eastern Cooperative Oncology Group (ECOG) Criteria of 0 or 1
• •4. Unsuitable for allogeneic stem cell transplantation
• •5. For participants who were born female who are of childbearing potential (FCBP) the following criteria apply:
• •1. Agreement to use at least two highly effective (per Clinical Trial Facilitation Group) contraceptive methods throughout the study, and for 6 months following the last dose of study drug:
• •* Oral/intravaginal/transdermal combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation
• •* Oral/injectable/implantable progestogen-only hormonal contraception associated with inhibition of ovulation
• •* Intrauterine device (IUD)
• •* Intrauterine hormone-releasing system (IUS)
• •* Bilateral tubal occlusion
• •* Vasectomised partner
• •* Sexual abstinence and
• •2. Confirmation of a negative serum pregnancy test at screening.
• •6. Male participants with a partner who was born female and is of childbearing potential must agree to use at least two highly effective (per Clinical Trial Facilitation Group) contraceptive methods throughout the course of the study and for 6 months following the last dose of study drug, and refrain from donating sperm during the same period
• •7. Provision of signed written informed consent document prior to any study related assessments or procedures being carried out.
• •15. Any of the following laboratory abnormalities:
• •1. Serum AST/SGOT (Aspartate transaminase / Serum glutamic oxaloacetic transaminase) or ALT/SGPT (Alanine aminotransaminase / Serum glutamic pyruvate transaminase) \> 2.5 x ULN (upper limit of normal)
• •2. Serum total bilirubin \> 1.5 x ULN. Patients with Gilbert syndrome may enroll if total bilirubin \< 51 umol/L upon discussion with the coordinating investigator
• •3. Evidence of autoimmune hemolytic anemia manifested as a corrected reticulocyte count of \> 2% with either a positive direct anti-globulin test (DAT) or over 50% of indirect bilirubin
• •4. Creatinine clearance \<50 ml/minute as calculated by the CockcroftGault formula or serum creatinine of ≥ 1.5 x ULN.
• •5. Absolute WBC (white blood cell count) ≥ 20 x 109/L f ) Participants with isolated individual lab abnormalities considered to be disease related will be considered individually in consultation with the Coordinating Principal Investigator.
• •16. Known or suspected hypersensitivity to study drugs or their constituents.
• •17. Pregnant or breast-feeding.
• •18. Any condition not already outlined above which, in the opinion of the clinical investigator, would place the participant at risk if they participated or would jeopardise adherence or follow up or confound the ability to interpret study data.