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

Inclusion Criteria

• 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;
• Is ≥18 years or the minimum legal adult age (whichever is greater) and ≤75 years (at Screening);
• 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);
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (at the time the participant signs their first ICF);
• Presence of FLT3-ITD activating mutation in bone marrow (allelic ratio of ≥3% FLT3-ITD/total FLT3);
• Participant is receiving standard "7+3" induction chemotherapy regimen as specified in the protocol;
• Adequate renal function defined as: a. Creatinine clearance >50 mL/min, as calculated with the modified Cockcroft Gault equation
• Adequate hepatic function defined as:
• Total serum bilirubin (TBL) ≤1.5 × upper limit of normal (ULN) unless the participant has documented Gilbert's syndrome or the increase is related to increased unconjugated (indirect) bilirubin due to hemolysis;
• Serum alkaline phosphatase, aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 × ULN;
• Serum electrolytes within normal limits: potassium, calcium (total, or corrected for serum albumin in case of hypoalbuminemia or ionized calcium) and magnesium. If outside of normal limits, participant will be eligible when electrolytes are corrected;
• 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);
• 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

• 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); participants 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).
• Diagnosis of AML secondary to prior chemotherapy or radiotherapy for other neoplasms;
• 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;
• Prior treatment with quizartinib or other FLT3-ITD inhibitors;
• 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;
• History of known CNS leukemia, including cerebrospinal fluid positive for AML blasts; lumbar puncture is recommended for participants with symptoms of CNS leukemia to rule out extramedullary CNS involvement;
• 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;
• Uncontrolled or significant cardiovascular disease, including any of the following:
• Bradycardia of less than 50 beats per minute, unless the participant 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 (participants 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;
• Active acute or chronic systemic fungal, bacterial, or viral infection not well controlled by antifungal, antibacterial or antiviral therapy;
• Known active clinically relevant liver disease (eg, active hepatitis B, or active hepatitis C);
• Known history of human immunodeficiency virus (HIV). Participants should be tested for HIV prior to Randomization if required by local regulations or EC;
• History of hypersensitivity to any excipients in the quizartinib/placebo tablets;
• Females who are pregnant or breastfeeding;
• Otherwise considered inappropriate for the study by the Investigator.