Safety and Efficacy of Quizartinib in Children and Young Adults With Acute Myeloid Leukemia (AML), a Cancer of the Blood

Inclusion Criteria:

Participants must meet all of the following criteria to be eligible for enrollment into the study:

• Has diagnosis of AML according to the World Health Organization (WHO) 2008classification with ≥5% blasts in bone marrow, with or without extramedullarydisease

• In first relapse or refractory to first-line high-dose chemotherapy with no morethan 1 attempt (1 to 2 cycles of induction chemotherapy) at remission induction -prior HSCT is permitted

• Has presence of the FLT3-ITD activating mutation in bone marrow or peripheral bloodas defined in the protocol

• Is between 1 month and 21 years of age at the time the Informed Consent/Assent formis signed

• Has protocol-defined adequate performance status score

• Has fully recovered from the acute clinically significant toxicity effects of allprior chemotherapy, immunotherapy, or radiotherapy, per protocol guidelines

• Has protocol-defined adequate renal, hepatic and cardiac functions

• If of reproductive potential, is permanently sterile or agrees to use highlyeffective birth control upon enrollment, during the period of therapy, and for 6months following the last dose of quizartinib, etoposide, fludarabine, methotrexate,or cytarabine, whichever is later

• If female of child-bearing potential, tests negative for pregnancy and agrees not tobreast feed

• Male participants must be surgically sterile or willing to use highly effectivebirth control during the treatment period, and for 6 months following the last doseof quizartinib, etoposide, fludarabine, methotrexate, or cytarabine, whichever islater.

• Participant/legal representative is capable of understanding the investigationalnature of the study, potential risks, and benefits, and the patient (and/or legalrepresentative) signs a written assent/informed consent

Exclusion Criteria:

Participants who meet any of the following criteria will be disqualified from entering the study:

• Has been diagnosed with isolated central nervous system relapse, acute promyelocyticleukemia (APL), juvenile myelomonocytic leukemia, French-American-Britishclassification M3 or WHO classification of APL with translocation, or with myeloidproliferations related to Down syndrome

• Has uncontrolled or pre-defined significant cardiovascular disease as detailed inthe protocol

• Has systemic fungal, bacterial, viral or other infection that is exhibiting ongoingsigns/symptoms related to the infection without improvement despite appropriateantibiotics or other treatment. The patient must be off vasopressors and havenegative blood cultures for at least 48 hours prior to the start of systematicprotocol therapy.

• Has known active clinically relevant liver disease (e.g., active hepatitis B oractive hepatitis C)

• Has known history of human immunodeficiency virus (HIV)

• Has history of hypersensitivity to any of the study medications or their excipients

• Is receiving or is anticipated to receive concomitant chemotherapy, radiation, orimmunotherapy other than as specified in the protocol

• Has any significant concurrent disease, illness, psychiatric disorder or socialissue that would compromise subject safety or compliance, interfere withconsent/assent, study participation, follow up, or interpretation of study results

• Is currently participating in another investigative interventional procedure (observational or long-term interventional follow-up is allowed)

• Is otherwise considered inappropriate for the study by the Investigator