Open Label Study to Evaluate Safety and Efficacy of 2 Doses of Quizartinib in Patients With Relapsed or Refractory Acute Myeloid Leukemia

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

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:

- 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

- 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:

- 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