The primary objective of the study is to determine whether quizartinib monotherapy prolongs
overall survival (OS) compared to salvage chemotherapy in subjects with FMS-like tyrosine
kinase 3 - Internal Tandem Duplication (FLT3-ITD) positive AML who are refractory to or have
relapsed within 6 months, after first-line AML therapy.
1. Provision of written informed consent approved by the Institutional Review Board (IRB)
or Independent Ethics Committee (IEC) with privacy language in accordance with
national regulations (e.g., Health Insurance Portability and Accountability Act
[HIPAA] authorization for United States [US] sites) prior to any study related
procedures, including withdrawal of prohibited medications if applicable.
2. Age ≥ 18 years or the minimum legal adult age (whichever is greater) at the time of
3. Morphologically documented primary Acute Myeloid Leukemia (AML) or AML secondary to
Myelodysplastic Syndrome (MDS), as defined by World Health Organization (WHO)
criteria, as determined by pathology review at the study site.
4. In first relapse (with duration of remission of 6 months or less) or refractory after
prior therapy, with or without HSCT. Induction therapy must have included at least 1
cycle of an anthracycline/mitoxantrone-containing induction block at a standard dose.
5. Presence of the FLT3-ITD activating mutation in bone marrow or peripheral blood
(allelic ratio as determined by a central laboratory with a cutoff of ≥3%
FLT3-ITD/total FLT3). If a specimen has been sent for FLT3-ITD testing at the central
laboratory but the subject requires treatment for AML before the central FLT3-ITD test
result is available, a local test result may be acceptable for randomization after
consultation with the Medical Monitor.
6. Eligibility for pre-selected salvage chemotherapy, according to the Investigator's
7. Eastern Cooperative Oncology Group (ECOG) performance score 0-2.
8. Discontinuation of prior AML treatment before the start of study treatment (except
hydroxyurea or other treatment to control leukocytosis) for at least 2 weeks for
cytotoxic agents, or for at least 5 half-lives for non cytotoxic agents.
9. Serum creatinine ≤1.5×upper limit of normal (ULN), or glomerular filtration rate >25
mL/min, as calculated with the Cockcroft-Gault formula.
10. Serum potassium, magnesium, and calcium (serum calcium corrected for hypoalbuminemia)
within institutional normal limits. Subjects with electrolytes outside the normal
range will be eligible if these values are corrected upon retesting following any
11. Total serum bilirubin ≤1.5×ULN.
12. Serum aspartate transaminase (AST) and/or alanine transaminase (ALT) ≤2.5×ULN.
1. Acute Promyelocytic Leukemia (AML subtype M3).
2. AML secondary to prior chemotherapy for other neoplasms, except AML secondary to prior
Myelodysplastic Syndrome (MDS).
3. History of another malignancy, unless the candidate has been disease-free for at least
4. Persistent, clinically significant > Grade 1 non-hematologic toxicity from prior AML
5. Clinically significant graft versus host disease (GVHD) or GVHD requiring initiation
of treatment or treatment escalation within 21 days, and/or > Grade 1 persistent or
clinically significant non hematologic toxicity related to HSCT.
6. History of or current, central nervous system involvement with AML.
7. Clinically significant coagulation abnormality, such as disseminated intravascular
8. Prior treatment with quizartinib or participated in a prior quizartinib study.
9. Prior treatment with a FLT3 targeted therapy including sorafenib or investigational
FLT3 inhibitors (not including the multi-kinase inhibitor, midostaurin).
10. Major surgery within 4 weeks prior to screening.
11. Radiation therapy within 4 weeks prior to screening.
12. Uncontrolled or significant cardiovascular disease
13. Active infection not well controlled by antibacterial or antiviral therapy.
14. Known infection with human immunodeficiency virus, or active hepatitis B or C, or
other active clinically relevant liver disease.
15. Unwillingness to receive infusion of blood products according to the protocol.
16. In a man whose sexual partner is a woman of childbearing potential, unwillingness or
inability of the man or woman to use a highly effective contraceptive method for the
entire study treatment period for at least 3 months after study completion. Male
subjects must not freeze or donate sperm starting at Screening and throughout the
study period, and 105 days after the final study drug administration.
17. In a heterosexually active woman of childbearing potential, unwillingness or inability
to use a highly effective contraceptive method for the entire study treatment period
and for at least 3 months after study treatment completion. Additionally, for women
randomized to chemotherapy, unwillingness to adhere to the restrictions in the
respective locally established guidelines and local approved label (prescribing
information, Summary of Product Characteristics, or US product insert) from the
manufacturer and the Patient Information Leaflet (package insert) as instructed by the
19. Female Subjects must agree to not breastfeed from the time of Screening and throughout
the study period, and for 25 days after the final study drug administration.
20. Medical condition, serious intercurrent illness, or other circumstance that, in the
Investigator's judgment, could jeopardize the candidate's safety as a study subject,
or that could interfere with study objectives.
21. For subjects in the UK only: Refusal of permission to allow the subject's General
Practitioner to be notified of their participation in the study.