|Inclusion Criteria:||1) Patients 18 years or older with Philadelphia chromosome (Ph)-positive or BCR-ABL1-positive CML (as determined by cytogenetics, fluorescent in situ hybridization [FISH], or polymerase chain reaction [PCR]) in CP resistant to at least 2 of the 3 FDA-approved TKIs (i.e., imatinib, nilotinib, dasatinib) or in AP or BP (either newly diagnosed or TKI-resistant), relapsed/refractory MDS, AML, or PMF, Post-polycythemia vera (PV) or Post-essential thrombocythemia (ET) myelofibrosis (with intermediate-1, intermediate-2 or high risk disease according to the International Working Group [IWG] prognostic scoring system).|
2) Performance status 0-2 of the Eastern Cooperative Oncology Group (ECOG) scale
3) 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
4) Adequate organ function: a) serum creatinine </=2.0 mg/dl or calculated creatinine clearance >/=60 mL/min; b) Total bilirubin </=2xULN (</=5xULN if considered due to Gilbert's syndrome or hemolysis); c) alanine aminotransferase (ALT) </=3xULN
5) Patients must sign an informed consent indicating that they are aware of the investigational nature of this study.
6) 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 [HCG]) within 7 days prior to the start of PRI-724.
7) 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, are eligible for the Phase II portion of the study.
8) Patients with CML-CP after failure of two FDA-approved TKIs (i.e., imatinib, nilotinib, dasatinib) or patients with CML in AP or BP either newly diagnosed or failing TKI therapy will be eligible to enroll in the Phase II study for patients with CML.