Quizartinib and Decitabine in Treating Participants With Untreated or Relapsed FLT3-ITD Mutated Acute Myeloid Leukemia or Myelodysplastic Syndrome

Inclusion Criteria:

1. Diagnosis of 1) AML (WHO classification definition of >/= 20% blasts) excluding acute
promyelocytic leukemia (APL) or 2) MDS with > 10% blasts (defined by the IPSS
classification).

2. For frontline Cohort: Patients aged >/= 60 years old who are not candidates for
intensive in duction therapy and agree to receive the proposed combination therapy
will be enrolled.

3. For relapsed cohort: Patients aged >/= 18 years old. (Patients who are candidates for
relapse cohort will be enrolled into the study regardless of their fitness for
intensive chemotherapy).

4. For frontline cohort: Patients must be chemonaive, i.e. not have received any
chemotherapy (except hydrea or 1-2 doses of ara-C for transient control of
hyperleukocytosis) for AML or MDS. They may have received transfusions, hematopoietic
growth factors or vitamins for an antecedent hematological disorder (AHD) or for AML.
Temporary prior measures such as apheresis, ATRA, steroids or hydrea while diagnostic
work-up is being performed are allowed and not counted as a prior salvage. Supportive
care therapy for MDS (growth factors, transfusions) will not be considered as prior
therapy for MDS/AML and these patients will be enrolled to the frontline cohort of the
study if they are otherwise eligible.

5. For relapsed cohort: Patients who have received at least one prior therapy for AML or
for MDS with > 10% blasts will be eligible. Patients may have received up to 3 prior
regimens for AML and/or MDS (defined by the IPSS classification). Prior therapy for
AML or MDS will be counted as a prior salvage. Patients who receive MDS directed
therapies considered not purely supportive such as HMAs, lenalidomide, investigational
therapies, will be enrolled to the salvage cohort if they are otherwise eligible.

6. In the absence of rapidly progressing disease, the interval from prior treatment to
time of initiation of protocol therapy will be at least 2 weeks for cytotoxic agents
or at least 5 half-lives for cytotoxic/noncytotoxic agents. The half-life for the
therapy in question will be based on published pharmacokinetic literature and will be
documented in the protocol eligibility document.

7. The use of chemotherapeutic or anti-leukemic agents is not permitted during the study
with the following exceptions: (1) intrathecal (IT) therapy for patients with
controlled CNS leukemia at the discretion of the PI and with the agreement of the
Sponsor. Controlled CNS leukemia is defined by the absence of active clinical signs of
CNS disease and no evidence of CNS leukemia on the most recent 2 simultaneous CSF
evaluations (2) Use of one dose of cytarabine (up to 2 g/m^2) or hydroxyurea for
patients with rapidly proliferative disease is allowed before the start of study
therapy and for the first four weeks on therapy. These medications will be recorded in
the case-report form.

8. Detection of FLT3-ITD mutation or FLT3-ITD/TKD co-mutations in bone marrow and/or
peripheral blood samples within 30 days prior to study enrollment

9. ECOG performance status
10. Serum biochemical values with the following limits unless considered due to leukemia,
hemolysis or congenital disorder (Creatinine < 1.8 mg/dl, Total bilirubin < 1.8 mg/dL,
(SGPT) <2.5x upper limit of normal)

11. Ability to take oral medication.

12. Ability to understand and provide signed informed consent.

13. Baseline left ventricular ejection fraction by ECHO or MUGA >/= 50%.

14. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy
test within 7 days. Men must agree not to father a child and agree to use a condom if
his partner is of child bearing potential.

15. WOCBP must use appropriate method(s) of contraception. WOCBP should use an adequate
method to avoid pregnancy until at least 3 months after the last dose of
investigational drug. Women who are not of childbearing potential (ie, who are
postmenopausal or surgically sterile) as well as men with azoospermia do not require
contraception.

16. Negative urine or serum pregnancy test.

Exclusion Criteria:

1. Patients with known allergy or hypersensitivity to quizartinib, mannitol, decitabine
or any of their components.

2. Prior quizartinib use

3. Patients with known uncontrolled CNS leukemia

4. Only for frontline cohort: patients who are fit for intensive chemotherapy

5. Patients with electrolyte abnormalities at study entry defined as follows: Serum
potassium < 3.5 mEq/L despite supplementation, or > 5.5 mEq/L Serum magnesium above or
below the institutional normal limit despite adequate management. Serum calcium
(corrected for albumin levels) above or below institutional normal limit despite
adequate management

6. Patients with known significant impairment of gastrointestinal (GI) function or GI
disease that may significantly alter the absorption of quizartinib

7. Patients with any other known concurrent severe and/or uncontrolled medical condition
including but not limited to diabetes, cardiovascular disease including hypertension,
renal disease, or active uncontrolled infection, which could compromise participation
in the study. Patients on active antineoplastic or radiation therapy for a concurrent
malignancy at the time of screening. Maintenance therapy, hormonal therapy, or steroid
therapy for well-controlled malignancy is allowed.

8. Patients with a known HIV infection

9. Patients with known positive hepatitis B or C infection by serology, with the
exception of those with an undetectable viral load within 3 months. (Hepatitis B or C
testing is not required prior to study entry). Subjects with serologic evidence of
prior vaccination to HBV [i.e., HBs Ag-, and anti-HBs+] may participate.

10. Patients who have consumed grapefruit, grapefruit products, Seville oranges (including
marmalade containing Seville oranges) or Starfruit within 3 days prior to the
initiation of study treatment.

11. Patients who have had any major surgical procedure within 14 days of Day 1.

12. Impaired cardiac function including any of the following: Screening ECG with a QTc>450
msec. The QTc interval will be calculated by Fridericia's correction factor (QTcF) at
Screening and on Day 5 prior to the first dose of AC220. The QTcF will be derived from
the average QTcF in triplicate. If QTcF>450 msec on Day 5, AC220 will not be given.
Patients with congenital long QT syndrome. History or presence of sustained
ventricular tachycardia requiring medical intervention. Any history of clinically
significant ventricular fibrillation or torsades de pointes. Known history of second
or third degree heart block (may be eligible if the patient currently has a
pacemaker). Sustained heart rate of < 50/minute on pre-entry ECG. Right bundle branch
block + left anterior hemiblock (bifascicular block). complete left bundle branch
block. Patients with myocardial infarction or unstable angina within 6 months prior to
starting study drug. CHF NY Heart Association class III or IV. (continued below)

13. (cont) Atrial fibrillation documented within 2 weeks prior to first dose of study
drug. Patients who are actively taking a strong CYP3A4 inducing medication [see
appendix]

14. Patients who require treatment with concomitant drugs that prolong QT/QTc interval or
strong CYP3A4 inhibitors 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 or if
the Investigator believes that beginning therapy with a potentially QTc-prolonging
medication (such as anti-emetic) is vital to an individual subject's care while on
study.

15. Known family history of congenital long QT syndrome.