Phase 2b study of 2 dosing regimens of quizartinib monotherapy in FLT3-ITD–mutated, relapsed or refractory AML

Jorge E. Cortes*, Martin S. Tallman, Gary J. Schiller, Denise Trone, Guy Gammon, Stuart L. Goldberg, Alexander E. Perl, Jean Pierre Marie, Giovanni Martinelli, Hagop M. Kantarjian, Mark J. Levis

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

94 Scopus citations

Abstract

This randomized, open-label, phase 2b study (NCT01565668) evaluated the efficacy and safety of 2 dosing regimens of quizartinib monotherapy in patients with relapsed/ refractory (R/R) FLT3-internal tandem duplication (ITD)–mutated acute myeloid leukemia (AML) who previously underwent transplant or 1 second-line salvage therapy. Patients (N 5 76) were randomly assigned to 30- or 60-mg/day doses (escalations to 60 or 90 mg/day, respectively, permitted for lack/loss of response) of single-agent oral quizartinib dihydrochloride. Allelic frequency of at least 10% was defined as FLT3-ITD–mutated disease. Coprimary endpoints were composite complete remission (CRc) rates and incidence of QT interval corrected by Fridericia’s formula (QTcF) of more than 480 ms (grade 2 or greater). Secondary endpoints included overall survival (OS), duration of CRc, bridge to transplant, and safety. CRc rates were 47% in both groups, similar to earlier reports with higher quizartinib doses. Incidence of QTcF above 480 ms was 11% and 17%, and QTcF above 500 ms was 5% and 3% in the 30- and 60-mg groups, respectively, which is less than earlier reports with higher doses of quizartinib. Median OS (20.9 and 27.3 weeks), duration of CRc (4.2 and 9.1 weeks), and bridge to transplant rates (32% and 42%) were higher in the 60-mg groups than in the 30-mg group. Dose escalation occurred in 61% and 14% of patients in the 30- and 60-mg groups, respectively. This high clinical activity of quizartinib at the evaluated doses is consistent with previous reports with an improved safety profile. Need to dose-escalate more than half of patients who received quizartinib 30 mg also supports further investigation of treatment with quizartinib 60 mg/day.

Original languageEnglish (US)
Pages (from-to)598-607
Number of pages10
JournalBlood
Volume132
Issue number6
DOIs
StatePublished - Aug 9 2018

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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