{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T22:39:24Z","timestamp":1792449564989,"version":"4.5.0"},"reference-count":42,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,12,4]],"date-time":"2017-12-04T00:00:00Z","timestamp":1512345600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002973","name":"Daiichi-Sankyo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002973","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Novel therapies have potential to improve outcomes in patients with acute myeloid leukemia (AML) harboring FLT3\u2010ITD mutations that have high risk of relapse and poor survival following standard of care (SOC) cytarabine\/anthracycline\u2010based induction\/consolidation chemotherapy. Quizartinib is a selective and highly potent FLT3 inhibitor that has shown strong single\u2010agent activity in relapsed or refractory (R\/R) AML. This phase 1, open\u2010label, sequential group dose\u2010escalation trial (NCT 01390337) is the first evaluating safety and tolerability of quizartinib in combination with SOC chemotherapy in newly diagnosed AML (ndAML). Nineteen patients unselected for FLT3 mutational status received one of three quizartinib dihydrochloride dose levels (DL): 60 mg\/d for 7 days (DL1; <jats:italic>n<\/jats:italic>\u2009=\u20096), 60 mg\/d for 14 days (DL2; <jats:italic>n<\/jats:italic>\u2009=\u20097), and 40 mg\/d for 14 days (DL\u20101; <jats:italic>n<\/jats:italic>\u2009=\u20096); administered orally starting on day 4 of chemotherapy. Median age was 43.8 years. Ten patients completed induction and consolidation. Three patients experienced dose\u2010limiting toxicities (DLTs): 2 at DL2 (1 pericardial effusion; 1 febrile neutropenia, decreased platelet count, and QT prolongation); 1 at DL\u20101 (pericarditis). Maximum tolerated dose (MTD) was identified as DL\u20101. Most common grade 3\/4 adverse events were febrile neutropenia (47%), neutropenia (42%), thrombocytopenia (32%), and anemia (26%). There were no apparent additional toxicities with addition of quizartinib to chemotherapy although grade \u22641 QT prolongation was observed at MTD. Sixteen patients (84%) achieved a response; 14 (74%) composite complete response; 2 (11%) morphologic leukemia\u2010free state. The phase 3 QuANTUM\u2010First trial (NCT02668653) is further evaluating the effect of quizartinib plus SOC chemotherapy in ndAML FLT3\u2010ITD mutated patients.<\/jats:p>","DOI":"10.1002\/ajh.24974","type":"journal-article","created":{"date-parts":[[2017,11,15]],"date-time":"2017-11-15T08:26:39Z","timestamp":1510734399000},"page":"213-221","source":"Crossref","is-referenced-by-count":79,"title":["Phase 1 study of quizartinib in combination with induction and consolidation chemotherapy in patients with newly diagnosed acute myeloid leukemia"],"prefix":"10.1002","volume":"93","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1987-1896","authenticated-orcid":false,"given":"Jessica K.","family":"Altman","sequence":"first","affiliation":[{"name":"Robert H. 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