Safety and Efficacy Study of PRI-724 in Subjects With Advanced Myeloid Malignancies

Inclusion Criteria 1. Patients 18 years or older 2. Part I: Patients with one of the following histologically- or cytologically-proven conditions: relapsed/refractory AML, relapsed/refractory MDS, or advanced CML in AP or BP (i.e., Acute Group patients). 3. Part II: Patients with one of the following documented conditions: CML in CP that is Philadelphia chromosome (Ph)-positive (by cytogenetics) or BCR-ABL1-positive by fluorescent in situ hybridization \[FISH\], or PCR), as well as resistant to at least 2 FDA-approved tyrosine kinase inhibitors (TKIs); or a myeloproliferative neoplasia which includes: PMF and myelofibrosis secondary to polycythemia vera (PV) and essential thrombocythemia (ET) myelofibrosis (MF) (with intermediate-1, intermediate-2 or high risk disease according to the International Working Group \[IWG\] prognostic scoring system) (i.e., Non-Acute Group patients). 4. Part III: * Arm A: Patients with AML who are 65 years of age or older with refractory or relapsed disease, or who have not received prior therapy but are not eligible to receive intensive frontline chemotherapy (i.e., Acute Group patients); * Arm B: Patients with CML in AP or BP, either newly diagnosed or failing TKI therapy (i.e., Acute Group patients); * Arm C: Patients with CML in CP after failure of 2 FDA-approved TKIs (i.e., Non-Acute group patients) 5. Performance status 0-2 of the Eastern Cooperative Oncology Group (ECOG) scale 6. Patients must have been off all prior therapy for leukemia except hydroxyurea for 1 week prior to entering this study and recovered from the toxic effects of that therapy 7. Adequate organ function as defined by: * Serum creatinine ≤ 2.0 mg/dL or calculated creatinine clearance ≥60 mL/min * Total bilirubin ≤2 x ULN (≤5 x ULN if considered due to Gilbert's syndrome or hemolysis) * Alanine aminotransferase (ALT) ≤3xULN 8. Patients must sign an informed consent indicating that they are aware of the investigational nature of this study. 9. Women of childbearing potential and men should practice effective methods of contraception. Women of childbearing potential should have a negative urine or serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin within 7 days prior to the start of PRI 724. Exclusion Criteria 1. Patients receiving any other investigational agents 2. Patients who are pregnant or breast-feeding 3. Known hypersensitivity to any of the components of PRI-724 4. Pretreatment QTcF interval \>470 msec (females) or \>450 msec (males) 5. Known active hepatitis B, hepatitis C 6. Serious uncontrolled medical disorder or active systemic infection or current unstable or decompensated medical condition, which makes it undesirable or unsafe for the patient to participate in the study including: New York Heart Association (NYHA) Class 3 or 4, myocardial infarction within 3 months, uncontrolled angina within 3 months, history of clinically significant ventricular arrhythmia, diabetes mellitus with ketoacidosis, or chronic obstructive pulmonary disease (COPD) requiring hospitalization in 6 months prior to the start of treatment with PRI-724. 7. Any other condition, including mental illness or substance abuse deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate, and participate in the study 8. Patients on full dose anticoagulants or any dose of warfarin; patients on prophylactic dose of low-molecular weight or unfractionated heparin are allowed. 9. Patients who have demonstrated intolerance to dasatinib 100 mg daily will not be eligible for Part III/Arm B or C of the study.