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


Authors: Cortes, J. E.; Tallman, M. S.; Schiller, G. J.; Trone, D.; Gammon, G.; Goldberg, S. L.; Perl, A. E.; Marie, J. P.; Martinelli, G.; Kantarjian, H. M.; Levis, M. J.
Article Title: Phase 2b study of 2 dosing regimens of quizartinib monotherapy in FLT3-ITD - mutated, relapsed or refractory AML
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. Copyright 2011 by The American Society of Hematology; all rights reserved.
Journal Title: Blood
Volume: 132
Issue: 6
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2018-08-09
Start Page: 598
End Page: 607
Language: English
DOI: 10.1182/blood-2018-01-821629
PROVIDER: scopus
PMCID: PMC6085992
PUBMED: 29875101
DOI/URL:
Notes: Article -- Export Date: 4 September 2018 -- Source: Scopus
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MSK Authors
  1. Martin Stuart Tallman
    443 Tallman