This study will compare the effects of Quizartinib versus placebo in combination with chemotherapy in participants with newly diagnosed FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) negative acute myeloid leukemia (AML).

This is a clinical trial to compare the effect of quizartinib versus placebo (administered with standard induction and consolidation chemotherapy, then administered as maintenance therapy for up to 36 cycles) on the primary endpoint of overall survival (OS) in adult patients with newly diagnosed FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) negative acute myeloid leukemia (AML). Participants will be tested for FLT3-ITD mutation status in a central laboratory using a validated assay.

Key Inclusion Criteria:

1. Must be competent and able to comprehend, sign, and date an Ethics Committee (EC)- or Institutional Review Board (IRB)-approved ICF before performance of any trial-specific procedures or tests.
2. ≥18 years or the minimum legal adult age (whichever is greater) and ≤70 years (at Screening).
3. Newly diagnosed, morphologically documented primary AML based on the World Health Organization (WHO) 2016 classification (at Screening)
4. Eastern Cooperative Oncology Group (ECOG) performance status (at the time the participant signs their ICF) of 0-2.
5. Participant is a candidate for standard "7+3" induction chemotherapy regimen as specified in the protocol per investigator assessment

Key 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 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).

2. Diagnosis of AML secondary to prior chemotherapy or radiotherapy.

3. Diagnosis of AML with known antecedent myelodysplastic syndrome (MDS) or a myeloproliferative neoplasm (MPN) or MDS/MPNs including chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia (aCML), juvenile myelomonocytic leukemia (JMML) and others.

4. Participants with newly diagnosed AML with FLT3-ITD mutations (FLT3-ITD [+]) present at ≥5% VAF (or ≥0.05 SR) based on a validated FLT3 mutation assay.

5. Prior treatment for AML, except for the following allowances prior to Day 1 of chemotherapy:

   1. Leukapheresis;
   2. Treatment for hyperleukocytosis with hydroxyurea;
   3. Cranial radiotherapy for central nervous system (CNS) leukostasis;
   4. Prophylactic intrathecal chemotherapy

De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

Completed studies that has reached a global end or completion with all data set collected and analyzed, and for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.

Formal request from qualified scientific and medical researchers on IPD and clinical study documents on completed clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.

This study has a double-blind design. Neither the participants nor any of the investigators, Sponsor, Independent Review Committee (IRC) or contract research organizations (CROs) will be aware of the treatments received. An independent biostatistician, not otherwise part of the Sponsor trial team, will generate the randomization schedule.