Expanded Treatment Protocol for Adults With FLT3-ITD Mutated Relapsed or Refractory Acute Myeloid Leukemia (AML) to Receive Quizartinib

Inclusion Criteria: Participants must satisfy all of the following inclusion criteria prior to receivetreatment:

1. Has provided written informed consent as approved per local regulations with privacylanguage in accordance with national regulations (eg, Health Insurance Portability andAccountability Act [HIPAA] authorization for US sites) prior to any protocol-relatedprocedures

2. Is 18 years of age or the minimum legal adult age (whichever is greater) at the timeof informed consent

3. Has morphologically documented primary AML or AML secondary to myelodysplasticsyndrome (MDS) or other myeloproliferative neoplasms (MPN), as defined by the WorldHealth Organization (WHO) 2008 classification with ≥5% blasts in bone marrow, with orwithout extramedullary disease

4. Is in relapse or refractory (R/R) to prior therapy, with or without HSCT

5. Refractory is defined as:

• participant did not achieve complete remission (CR), CR with incompleteplatelet recovery (CRp), or CR with incomplete hematological recovery (CRi)under initial intensive therapy, or

• did not achieve CR, CRp, CRi, or partial remission (PR) under initialsufficient time course of treatment with hypomethylating agents or low-dosecytarabine (LoDAC)

• must have received at least one complete block of induction therapy seen asthe optimum choice of therapy to induce remission or at least 4 cycles oftherapy with a hypomethylating agent deemed sufficient to induce a response

2. Relapse is defined as: relapse diagnosed by bone marrow assessment or by theappearance of peripheral blasts after the achievement of CR, CRp, or CRi, asdefined by 2003 International Working Group criteria after AML therapy with orwithout consolidation or maintenance, and with or without HSCT

3. Has documented FLT3-ITD mutation in bone marrow or peripheral blood in relation R/Rdisease

4. Prior treatment with kinase inhibitors, including FLT3 targeted therapy orinvestigational FLT3 inhibitors is allowed

5. Has an Eastern Cooperative Oncology Group (ECOG) performance score 0-3

6. Discontinued prior AML treatment before the start of protocol treatment (excepthydroxyurea or other treatment to control leukocytosis) for at least 2 weeks forcytotoxic agents, or for at least 5 half-lives for non-cytotoxic agents

7. Has creatinine clearance >25 mL/min, as calculated with the Cockcroft-Gault formula

8. Has serum potassium, magnesium, and calcium (serum calcium corrected forhypoalbuminemia) within institutional normal limits. Participants with electrolytesoutside the normal range will be eligible if these values are corrected upon retestingfollowing any necessary supplementation

9. Total serum bilirubin ≤1.5 × upper limit of normal (ULN)

10. Has serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤2.5 × ULN

Exclusion Criteria: Participants who meet any of the following criteria will be disqualified from enrollment:

1. Is eligible to enroll in a recruiting clinical trial of quizartinib or is currentlyenrolled in an ongoing clinical trial of quizartinib

2. Has previously participated in a randomized clinical study of quizartinib with anendpoint of survival that is not closed for efficacy

3. Has acute promyelocytic leukemia (AML subtype M3)

4. Has persistent, clinically significant ≥Grade 3 non-hematologic toxicity from priorAML therapy

5. Has clinically significant acute graft-versus-host disease (GvHD) or GVHD requiringinitiation of treatment or treatment escalation within 21 days, and/or ≥Grade 3persistent or clinically significant non-hematologic toxicity related to HSCT

6. Has uncontrolled or significant cardiovascular disease, including:

• QTcF interval >450 ms

• Bradycardia of less than 50 beats per minute (bpm) unless the patient has apacemaker

• Diagnosed or suspected long QT syndrome, or known family history of long QTsyndrome

• History of clinically relevant ventricular arrhythmias, such as ventriculartachycardia, ventricular fibrillation, or torsade de pointes

• History of second or third degree heart block. Candidates with a history of heartblock may be eligible if they currently have pacemakers, and have no history offainting or clinically relevant arrhythmia with pacemakers.

• Myocardial infarction within 6 months prior to screening

• Uncontrolled angina pectoris within 6 months prior to Screening

• New York Heart Association (NYHA) Class 3 or 4 congestive heart failure

• Left ventricular ejection fraction (LVEF) ≤45% or institutional lower limit ofnormal

• Uncontrolled hypertension

• Complete left bundle branch block

7. Has active infection not well controlled by antibacterial, antifungal, and/orantiviral therapy

8. Has active hepatitis B or C, or other active clinically relevant liver disease

9. Is unwilling to receive infusion of blood products according to the protocol

10. Women are regarded as of childbearing potential if they are not post-menopausal (atleast 2 years without menses) or surgically sterile (at least 1 month beforeenrollment). Highly effective contraception methods include: combined (estrogen and progestogencontaining) hormonal methods associated with inhibition of ovulation, intra-uterinedevice; surgical sterilization (including bilateral tubal occlusion, partner'svasectomy) or sexual abstinence if this is the preferred and usual lifestyle of theparticipant

11. If a heterosexually active woman of childbearing potential:

• Either partner is unwilling or unable to use a highly effectivecontraceptive method (as described above) for the entire treatment periodand for at least 6 months after the administration of the final dose ofquizartinib

• Is unwilling to refrain from donating or retrieving ova for her own use fromthe time of Screening and throughout the treatment period, and for 12 weeksafter the administration of the final dose of quizartinib

• Is pregnant - quizartinib should be permanently discontinued if pregnancy isconfirmed

• Is unwilling to refrain from breastfeeding from the time of Screening andthroughout the protocol period, and for 25 days after the administration ofthe final dose of quizartinib

2. If a man whose sexual partner is a woman of childbearing potential:

• Either partner is unwilling or unable to use a highly effectivecontraceptive method (as described above) for the entire treatment periodand for at least 6 months after completion of protocol treatment

• Is unwilling to refrain from freezing or donating sperm starting atScreening and throughout the treatment period and 105 days after theadministration of the final dose of quizartinib

11. Has any medical condition, serious intercurrent illness, or other circumstance that,in the treating physician's judgment, could jeopardize the participant's safety