Phase I Study of Quizartinib Administered Daily to Patients With Relapsed or Refractory Acute Myeloid Leukemia Irrespective of FMS-Like Tyrosine Kinase 3–Internal Tandem Duplication Status

Purpose FMS-like tyrosine kinase 3–internal tandem duplication (FLT3-ITD) mutations in acute myeloid leukemia (AML) are associated with early relapse and poor survival. Quizartinib potently and selectively inhibits FLT3 kinase activity in preclinical AML models. Patients and Methods Quizartinib was administered orally at escalating doses of 12 to 450 mg/day to 76 patients (median age, 60 years; range, 23 to 86 years; with a median of three prior therapies [range, 0 to 12 therapies]), enrolled irrespective of FLT3-ITD mutation status in a phase I, first-in-human study in relapsed or refractory AML. Results Responses occurred in 23 (30%) of 76 patients, including 10 (13%) complete remissions (CR) of any type (two CRs, three CRs with incomplete platelet recovery [CRp], five CRs with incomplete hematologic recovery [CRi]) and 13 (17%) with partial remissions (PRs). Of 17 FLT3-ITD–positive patients, nine responded (53%; one CR, one CRp, two CRis, five PRs); of 37 FLT3-ITD–negative patients, five responded (14%...