APR-246 & Azacitidine for the Treatment of TP53 Mutant Myelodysplastic Syndromes (MDS)

Inclusion Criteria: * Signed Informed Consent (ICF) and is able to comply with protocol requirements * Documented diagnosis of MDS, according to World Health Organization (WHO) classification * Patient has adequate organ function as defined by the following laboratory values: 1. Creatinine clearance \> 30 mL/min (by Cockcroft-Gault method) 2. Total serum bilirubin \< 1.5 x Upper Limit of Normal (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 * Age ≥18 years at the time of signing the informed consent form (ICF) * Having at least one TP53 mutation which is not benign or likely benign * Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2 * If of childbearing potential, negative pre-treatment urine or serum pregnancy test * 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: * Patient has a known history of human immunodeficiency virus (HIV) or active hepatitis B or active hepatitis C infection (testing not mandatory) * Patient has any of the following cardiac abnormalities (as determined by treating MD): 1. Myocardial infarct within six months prior to registration, 2. New York Heart Association Class II or worse heart failure (Appendix II) or known left ventricular ejection fraction (LVEF) \< the institution lower limit of normal as assessed by echocardiogram 3. A history of familial long QT syndrome, 4. Clinically significant pericardial disease 5. Electrocardiographic evidence of acute ischemia 6. Symptomatic atrial or ventricular arrhythmias not controlled by medications 7. QTc ≥ 470 msec (QT cardiac interval) 8. Bradycardia (\<40 bpm) * 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 * Prior exposure to azacitidine, decitabine or investigational hypomethylating agent * Prior exposure to intensive chemotherapy * Use of cytotoxic chemotherapeutic agents, or experimental agents (agents that are not commercially available) for the treatment of MDS within 14 days of the first day of study drug treatment * No concurrent use of erythroid stimulating agents * Patients with history of allogeneic stem cell transplantation * Pregnant women are excluded from this study because APR-246 has not been studied in pregnant patients. 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. * Patients with active uncontrolled infections