|Exclusion Criteria:||1) Subject received previous treatment with AC220.|
2) Subject has diagnosis of acute promyelocytic leukemia.
3) Subject has diagnosis of chronic myelogenous leukemia (CML) in blast crisis.
4) Subject has AML or antecedent MDS secondary to prior chemotherapy.
5) Subject has had HSCT and has either of the following: Is within 100 days of transplant; Is still taking immunosuppressive drugs; Has clinically significant graft-versus-host disease requiring treatment; Has Grade > 1 persistent nonhematological toxicity related to the transplant. Donor lymphocyte infusion (DLI) is not permitted during the study or </= 30 days prior to study entry.
6) Subject has clinically active CNS leukemia. A subject is considered eligible if CNS leukemia is controlled and subject is receiving intrathecal ( IT) therapy at study entry. Subjects should continue to receive IT therapy (or cranial radiation) as clinically indicated.
7) Subject has received concurrent chemotherapy, immunotherapy, or radiotherapy within 14 days prior to the first dose of AC220, or any ancillary therapy that is considered to be investigational (i.e., used for non-approved indications(s) and in the context of a research investigation) within 30 days or 5 half-lives (whichever is longer) prior to the first dose of study drug.
8) Subject requires treatment with concomitant drugs that prolong QT/QTc interval or with strong inhibitors or inducers of cytochrome P450-isozyme3A4 (CYP3A4) with the exception of antibiotics, antifungals, and antivirals that are used as standard of care post-transplant or to prevent or treat infections and other such drugs that are considered absolutely essential for the care of the subject.
9) Subject requires treatment with anticoagulant therapy.
10) Subject has a known positive test for human immunodeficiency virus, hepatitis C, or hepatitis B surface antigen.
11) Subject had major surgery within 4 weeks prior to first dose of AC220.
12) Subject has uncontrolled or significant cardiovascular disease, including: A myocardial infarction within 12 months prior to the start of study drug; Uncontrolled angina within 6 months prior to the start of study drug; History of congestive heart failure (CHF) New York Heart Association (NYHA) class 3 or 4. If a screening echocardiogram (ECHO) or Multiple Gate Acquisition Scan (MUGA) is performed within 1 month prior to, or during study screening and the result is a left ventricular ejection fraction (LVEF) that is >/= 45% (or MDACC lower limit of normal value which is 50%) then this is not exclusionary; Heart rate < 50 beats per minute at Screening ECG; Diagnosed or suspected congenital long QT syndrome; Known family history of congenital long QT syndrome; QTc interval calculated by Fridericia's correction factor (QTcF) at Screening >/= 450 ms. The QTcF will be derived from the average QTcF in triplicate;
13) **continued from above: Any history of second or third degree heart block; Uncontrolled hypertension defined as systolic blood pressure >/= 180 mmHg or diastolic blood pressure >/= 110 mmHg; Obligate need for a cardiac pacemaker or defibrillator; Complete left bundle branch block; Atrial fibrillation documented within 2 weeks prior to first dose of study drug; or History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia) that was symptomatic or required treatment (CTCAE Grade 3).
14) Subject has a pre-existing disorder predisposing the subject to a serious or life-threatening infection (e.g. cystic fibrosis, congenital or acquired immunodeficiency, bleeding disorder, or cytopenias).
15) Subject has an active uncontrolled acute or chronic systemic fungal, bacterial, viral, or other infection.
16) Subject has any of the following laboratory values: Serum potassium < 4.0 mmol/L despite supplementation, or > 5.5 mmol/L; Serum magnesium below the institutional normal limit despite supplementation, or > 3 mg/dL (1.23 mmol/L); Serum calcium > 11.5 mg/dL (2.9 mmol/L) or ionized calcium > 1.5 mmol/L.
17) Subject is a woman of childbearing potential (WOCBP) or a male subject with female partner of childbearing potential who is unwilling or unable to use an acceptable contraceptive method to avoid pregnancy for the entire study period and for at least 3 months after the last dose of study drug.
18) Subject is a female with a positive pregnancy test, pregnant, or breastfeeding.
19) Subject has any medical, psychiatric, addictive or other kind of disorder which compromises the ability of the subject to give written informed consent and/or to comply with procedures.