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

Exclusion Criteria

• •* 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.
• •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.