A Study to Assess AC220 Given in Combination With Induction and Consolidation Therapy in Newly Diagnosed Acute Myeloid Leukemia (AML)

Subjects will receive escalating doses of AC220 plus standard 7+3 cytarabine and daunorubicin
remission induction therapy. Subjects may receive up to 2 cycles of induction therapy.
Subjects who have a complete response (including complete remission (CR) with incomplete
hematologic recovery) are eligible to receive up to 3 consolidation cycles. In consolidation
subjects will receive AC220 plus high dose cytarabine. Subjects achieving a composite
Complete Remission (CRc) will be eligible to receive AC220 alone for up to 12 additional 28
day cycles.

Subjects will be enrolled into successive gender balanced cohorts of 6 subjects (at least 3
must be females) to determine the maximum tolerated dose (MTD). Dose escalation decision will
be made based on dose limiting toxicities (DLTs) that occur during the first remission
induction cycle. Seven and 14 day schedules will be evaluated.

After the MTD and schedule is established, the study will open to enroll between 14 to 34
subjects. Subjects will receive AC220 during induction and consolidation at the MTD and
schedule established. Stopping rules will be used to evaluate safety at the current dose. If
testing at a dose level must be stopped, then a lower dose may be tested. MTD will also be
established for the maintenance therapy.

Inclusion Criteria:

- Subject has a diagnosis of previously-untreated de novo acute myeloid leukemia (AML)
according to World Health Organization (WHO) classification (2008) documented within
28 days prior to enrollment and defined as > 20% myeloblasts on the marrow aspirate or
peripheral blood differential, with or without extramedullary involvement, with
confirmatory immunophenotyping or immunocytochemistry (e.g. myeloperoxidase). In
addition, subjects with the clonal, recurring cytogenetic abnormalities:
t(8;21)(q22;q22), inv(16)(p13q22) or t(16;16)(p13;q22) should be considered to have
AML regardless of the blast percentage. Subjects with both positive and negative
FMS-like tyrosine kinase - internal tandem duplication (FLT3-ITD) mutation status are
eligible.

- Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.

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

- Subject is a woman of childbearing potential (WOCBP) or a male subject with female
partner of childbearing potential who agrees to use a medically-approved method of
contraception to avoid pregnancy throughout the study and for at least 3 months after
the last dose of study drug.

- Subject is a WOCBP and has a negative serum or urine pregnancy test (sensitivity ≤ 25
IU human chorionic gonadotropin [hCG]/L) within 72 hours prior to the start of study
drug administration.

- Subject is able to comply with study procedures and follow-up examinations.

Exclusion Criteria:

- 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).

- Subject has a diagnosis of AML following an antecedent hematologic disorder (diagnosis
of myelodysplasia or myeloproliferative neoplasm by bone marrow aspirate and/or biopsy
documented at least 12 weeks prior to first dose of study drug).

- Subject has a diagnosis of acute bilineal/biphenotypic leukemia.

- Subject has therapy-related AML.

- Subject received previous treatment with AC220.

- Subject has received previous therapy for AML

- Subject has uncontrolled disseminated intravascular coagulation.

- Subject has Central Nervous System (CNS) leukemia. A Subject with symptoms suggestive
of CNS leukemia must undergo a lumbar puncture; and subject with a positive
cerebrospinal fluid (CSF) for AML blasts is not eligible.

- 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 the start of study drug.

- Subject has uncontrolled or significant cardiovascular disease - 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).

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

- 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.

- Subject requires treatment with concomitant drugs that prolong QT/QTc interval or
strong cytochrome P-3A4 (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.

- Subject requires treatment with anticoagulant therapy.

- Subject is a female who is lactating.

- 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.