|Exclusion Criteria:||1) Subject will be excluded from participation in Parts 1 and 2 if any of the following apply:|
2) Subject has a diagnosis of acute promyelocytic leukemia (APL), French-American- British (FAB) classification M3 or World Health Organization (WHO) classification of APL with t(15;17)(q22;q12), or BCR-ABL positive leukemia (chronic myelogenous leukemia in blast crisis).
3) Subject has a diagnosis of AML following an antecedent hematologic disorder (myelodysplasia or myeloproliferative neoplasm by bone marrow aspirate and/or biopsy documented at least 12 weeks prior to first dose of study drug).
4) Subject has a diagnosis of acute bilineal/biphenotypic leukemia.
5) Subject has therapy-related AML.
6) Subject received previous treatment with AC220.
7) Subject has received previous therapy for AML, with the exception of the following: Emergency leukapheresis; Emergency treatment for hyperleukocytosis with hydroxyurea for </= 5 days; Growth factor or cytokine support;Steroids for the treatment of hypersensitivity or transfusion reactions.
8) Subject has uncontrolled disseminated intravascular coagulation
9) Subject has CNS leukemia. A subject with symptoms suggestive of CNS leukemia must undergo a lumbar puncture; and a subject with a positive cerebrospinal fluid (CSF) for AML blasts is not eligible.
10) Subject has had 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 the start of study drug.
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, unless a screening echocardiogram (ECHO) or Multiple Gate Acquisition Scan (MUGA) performed either within 1 month prior to or during study screening results in a left ventricular ejection fraction (LVEF) that is >/= 45% (or institutional lower limit of normal value); Heart rate < 50 beats per minute at screening ECG; Diagnosed or suspected congenital long QT syndrome; Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes [TdP]) (any other history of arrhythmia will be discussed with the Sponsor's Medical Monitor prior to subject's entry into the study);
13) **continued from above: QTc interval calculated by Fridericia's correction factor (QTcF) at Screening and Day 4 pre-AC220 dose >/= 450 ms. The QTcF will be derived from the average QTcF in triplicate; 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; or Atrial fibrillation documented within 2 weeks prior to first dose of study drug.
14) Subject has a pre-existing disorder predisposing the subject to a serious or lifethreatening infection (e.g. cystic fibrosis, congenital or acquired immunodeficiency, bleeding disorder, or cytopenias).
15) Subject has an active acute or chronic systemic fungal, bacterial, viral, or other infection.
16) Subject has a concurrent disease (e.g. a history of serious organ dysfunction or disease) that may place the subject at undue risk to undergo induction therapy per protocol, or that might obscure assessments of drug safety.
17) Subject requires treatment with concomitant drugs that prolong QT/QTc interval or strong CYP3A4 inhibitors or inducers with the exception of antibiotics, antifungals, and antivirals that are used as standard of care to prevent or treat infections and other such drugs that are considered absolutely essential for the care of the subject.
18) Subject requires treatment with anticoagulant therapy.
19) Subject is a female who is lactating.
20) 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.
21) There are no exclusions for Part 3.