Inclusion Criteria:

          1. Patient has signed the Informed Consent (ICF) and is able to comply with protocol
             requirements.

          2. Patient has adequate organ function as defined by the following laboratory values:

               1. Serum creatinine ≤ 2 x upper limit of normal (ULN)

               2. Total serum bilirubin < 1.5 x ULN or total bilirubin ≤ 3.0 x ULN with direct
                  bilirubin within normal range in patients with well documented Gilbert's Syndrome
                  or hemolysis or who required regular blood transfusions

               3. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 x ULN

          3. Age ≥18 years at the time of signing the informed consent form

          4. Documented diagnosis of myelodysplastic syndrome (MDS), MDS/ myeloproliferative
             neoplasm (MPN), chronic myelomonocytic leukemia (CMML) by World Health organization
             (WHO) criteria or non-proliferative AML (ie with WBC < 20 G/l)

          5. Documentation of a TP53 gene mutation by next-generation sequencing (NGS) based on
             central or local evaluation.

          6. Revised International Prognostic Scoring System (IPSS-R) criteria for Intermediate,
             High-risk or Very High-risk.

          7. An Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2 is
             required.

          8. If of childbearing potential, negative pre-treatment urine or serum pregnancy test.

          9. If of childbearing potential (males and females), willing to use an effective form of
             contraception such as latex condom, hormonal birth control, intrauterine device or
             double barrier method during chemotherapy treatment and for at least six months
             thereafter.

        Exclusion Criteria:

          1. Patient has a known history of HIV or active hepatitis B or active hepatitis C
             infection (testing not mandatory).

          2. Patient has any of the following cardiac abnormalities (as determined by treating MD):

               1. symptomatic congestive heart failure

               2. myocardial infarction ≤ 6 months prior to enrollment

               3. unstable angina pectoris

               4. serious uncontrolled cardiac arrhythmia

               5. QTc ≥ 470 msec (≥ 500 msec in the presence of RBBB) calculated from a mean of 3
                  ECG readings using Fridericia's correction (QTcF = QT/RR0.33)

               6. bradycardia (<40 bpm)

               7. known left ventricular ejection fraction (LVEF) < the institution lower limit of
                  normal as assessed by ECHO

               8. clinically significant pericardial disease

               9. electrocardiographic evidence of acute ischemia

              10. familial history of long QT syndrome

          3. Concomitant malignancies or previous malignancies with less than a 1-year disease free
             interval at the time of signing consent. Patients with adequately resected basal or
             squamous cell carcinoma of the skin, or adequately resected carcinoma in situ (e.g.
             cervix) may enroll irrespective of the time of diagnosis.

          4. Prior exposure to azacitidine, decitabine or investigational hypomethylating agent

          5. Use of cytotoxic chemotherapeutic agents, or experimental agents (agents that are not
             commercially available) for the treatment of MDS, MDS/MPN, CMML or AML within 14 days
             of the first day of study drug treatment.

          6. No concurrent use of erythroid stimulating agents, Granulocyte-colony stimulating
             Factor (G-CSF), Granulocyte Macrophage-colony stimulating factor (GM-CSF) is allowed
             during study except in cases of febrile neutropenia where G-CSF can be used for short
             term. Growth factors must be stopped 14 days prior to study.

          7. Patients with history of allogeneic stem cell transplantation.

          8. Pregnant women are excluded from this study because APR-246 has not been studied in
             pregnant subjects. Because there is an unknown but potential risk for adverse events
             in nursing infants secondary to treatment of the mother with APR-246, breastfeeding
             should be discontinued if the mother is treated with APR-246.