Inclusion Criteria:

- Subject has morphologically documented primary AML or AML secondary to
myelodysplastic syndrome (MDS) as defined by the World Health Organization (WHO)
criteria, as determined by pathology review at the treating institution and has
relapsed or is refractory after 1 second line (salvage) regimen or after HSCT

- Subject is positive for FLT3-ITD activating mutation in bone marrow or peripheral
blood (>10% allelic ratio)

- ECOG performance status of 0 to 2

- In the absence of rapidly progressing disease clearly documented by the investigator,
the interval from prior treatment to time of AC220 administration will be at least 2
weeks (14 days) for prior cytotoxic agents or at least 5 half-lives for prior
noncytotoxic agents, including immunosuppressive therapy post HSCT

- Persistent chronic clinically significant nonhematological toxicities from prior
treatment (including chemotherapy, kinase inhibitors, immunotherapy, experimental
agents, radiation, HSCT, or surgery) must be Grade ≤ 1

- Patients - both males and females - with reproductive potential are eligible if the
following criteria is met:

- Female subject is:

- Post-menopausal (defined as at least 2 years without menses) prior to Screening
visit; or

- surgically sterile (at least 1 month prior to Screening visit; or

- of childbearing potential with contraception

- Female subject of childbearing potential has a negative pregnancy test at the
Screening visit and agrees to use contraception consisting of two forms of birth
control (one of which must be a barrier method) throughout the study period

- Male subject with partner(s) of childbearing potential must agree to use
contraception consisting of two forms of birth control (one of which must be a
barrier method) and agrees to no sperm donation throughout the study period

- Subject must have adequate renal, hepatic, and coagulation parameters as indicated by
the following laboratory values:

- Aspartate aminotransferase (AST), and alanine aminotransferase (ALT) ≤ 2.5 x
institutional upper limit of normal (ULN)

- Total bilirubin ≤ 1.5 x institutional ULN

- Serum creatinine ≤ 1.5 x institutional ULN and glomerular filtration rate (GFR)
> 30 mL/min (calculated by Cockcroft and Gault formula).

Exclusion Criteria:

- Subject received previous treatment with AC220

- Subject has a diagnosis of acute promyelocytic leukemia

- Subject has a diagnosis of chronic myelogenous leukemia (CML) in blast crisis

- Subject has AML or antecedent MDS secondary to prior chemotherapy

- 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 non hematological toxicity related to the transplant

- Donor lymphocyte infusion (DLI) is not permitted during the study or < 30 days prior
to study entry

- 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

- 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

- 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

- Subject requires treatment with anticoagulant therapy

- Subject has a known positive test for human immunodeficiency virus, hepatitis C, or
hepatitis B surface antigen

- Subject had major surgery within 4 weeks prior to first dose of AC220

- Subject has uncontrolled or significant cardiovascular disease, including

- A myocardial infarction 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
institutional lower limit of normal value); 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;

- 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)

- 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 not related to AML)

- Subject has an active uncontrolled acute or chronic systemic fungal, bacterial,
viral, or other infection

- 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

- Subject is a female with a positive pregnancy test, pregnant, or breastfeeding

- 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