Quizartinib With Standard of Care Chemotherapy and as Continuation Therapy in Patients With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia (AML)

This is a phase 3, randomized, double-blind, placebo-control global study. The purpose of
this study is to compare the effect of quizartinib versus placebo (administered with standard
induction and consolidation chemotherapy, then administered as continuation therapy for up to
36 cycles) on event-free survival in subjects with FLT3-internal tandem duplication (ITD)
positive AML.

Inclusion Criteria:

1. Must be competent and able to comprehend, sign, and date an Ethics Committee (EC) or
Institutional Review Board approved Informed Consent Form (ICF) before performance of
any study-specific procedures or tests;

2. Is ≥18 years or the minimum legal adult age (whichever is greater) and ≤75 years (at
Screening);

3. Newly diagnosed, morphologically documented primary AML or AML secondary to
myelodysplastic syndrome or a myeloproliferative neoplasm, based on the World Health
Organization (WHO) 2008 classification (at Screening);

4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (at the time the
subject signs their first informed consent form);

5. Presence of FLT3-ITD activating mutation in bone marrow (allelic ratio of ≥3%
FLT3-ITD/total FLT3);

6. Participant is receiving standard "7+3" induction chemotherapy regimen as specified in
the protocol;

7. Adequate renal function defined as:

a. Creatinine clearance >50 mL/min, as calculated with the modified Cockcroft Gault
equation

8. Adequate hepatic function defined as:

1. Total serum bilirubin (TBL) ≤1.5 × upper limit of normal (ULN);

2. Serum alkaline phosphatase, aspartate transaminase (AST) and alanine transaminase
(ALT) ≤2.5 × ULN;

9. Serum electrolytes within normal limits: potassium, calcium (total, or corrected for
serum albumin in case of hypoalbuminemia) and magnesium. If outside of normal limits,
subject will be eligible when electrolytes are corrected;

10. If a woman of childbearing potential, must have a negative serum pregnancy test upon
entry into this study and must be willing to use highly effective birth control upon
enrollment, during the treatment period and for 6 months following the last dose of
investigational drug or cytarabine, whichever is later. A woman is considered of
childbearing potential following menarche and until becoming postmenopausal (no
menstrual period for a minimum of 12 months);

11. If male, must be surgically sterile or willing to use highly effective birth control
upon enrollment, during the treatment period, and for 6 months following the last dose
of investigational drug or cytarabine, whichever is later.

Exclusion Criteria:

1. Diagnosis of acute promyelocytic leukemia (APL), French-American-British
classification M3 or WHO classification of APL with translocation, t(15;17)(q22;q12),
or breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1
(BCR-ABL) positive leukemia (ie, chronic myelogenous leukemia in blast crisis);
subjects who undergo diagnostic workup for APL and treatment with all-trans retinoic
acid (ATRA), but who are found not to have APL, are eligible (treatment with ATRA must
be discontinued before starting induction chemotherapy).

2. Diagnosis of AML secondary to prior chemotherapy or radiotherapy for other neoplasms;

3. Prior treatment for AML, except for the following allowances:

- Leukapheresis;

- Treatment for hyperleukocytosis with hydroxyurea;

- Cranial radiotherapy for central nervous system (CNS) leukostasis;

- Prophylactic intrathecal chemotherapy;

- Growth factor/cytokine support;

4. Prior treatment with quizartinib or other FLT3-ITD inhibitors;

5. Prior treatment with any investigational drug or device within 30 days prior to
Randomization (within 2 weeks for investigational or approved immunotherapy) or
currently participating in other investigational procedures;

6. History of known CNS leukemia, including cerebrospinal fluid positive for AML blasts;
lumbar puncture is recommended for subjects with symptoms of CNS leukemia to rule out
extramedullary CNS involvement;

7. History of other malignancies, except adequately treated non-melanoma skin cancer,
curatively treated in-situ disease, or other solid tumors curatively treated with no
evidence of disease for at least 2 years;

8. Uncontrolled or significant cardiovascular disease, including any of the following:

- Bradycardia of less than 50 beats per minute, unless the subject has a pacemaker;

- Fridericia's Heart Rate Correction Formula (QTcF) interval >450 msec;

- Diagnosis of or suspicion of long QT syndrome (including family history of long
QT syndrome);

- Systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥110 mmHg;

- History of clinically relevant ventricular arrhythmias (eg, ventricular
tachycardia, ventricular fibrillation, or Torsade de Pointes);

- History of second (Mobitz II) or third degree heart block (subjects with
pacemakers are eligible if they have no history of fainting or clinically
relevant arrhythmias while using the pacemaker);

- History of uncontrolled angina pectoris or myocardial infarction within 6 months
prior to Screening;

- History of New York Heart Association Class 3 or 4 heart failure;

- Known history of left ventricular ejection fraction (LVEF) ≤45% or less than the
institutional lower limit of normal;

- Complete left bundle branch block;

9. Active acute or chronic systemic fungal, bacterial, or viral infection not well
controlled by antifungal, antibacterial or antiviral therapy;

10. Known active clinically relevant liver disease (eg, active hepatitis B, or active
hepatitis C);

11. Known history of human immunodeficiency virus (HIV). Subjects should be tested for HIV
prior to Randomization if required by local regulations or EC;

12. History of hypersensitivity to any excipients in the quizartinib/placebo tablets;

13. Females who are pregnant or breastfeeding;

14. Otherwise considered inappropriate for the study by the Investigator.