Background
nausea, neutropenia, diarrhea, fatigue, toxicity, AML, vomiting, anemia, Allogeneic hematopoietic cell transplantation
ACUTE MYELOID LEUKEMIA, HEMATOLOGIC DISORDERS, NEUTROPENIA, FEBRILE NEUTROPENIA, ADVERSE EVENTS, THROMBOCYTOPENIA, DISEASE, AML, ANEMIA, REMISSION, GASTROINTESTINAL DISORDERS
Intensive chemotherapy consisting of induction and consolidation therapy is given with curative intent in most of the patients with acute myeloid leukemia (AML) except for old and frail patients [Allogeneic hematopoietic cell transplantation (allo-HCT) is currently the only treatment strategy to offer the prospect of a cure in relapsed/refractory (r/r-) AML. The outcome of allo-HCT is heavily influenced by the remission state before allo-HCT [Internal tandem duplications of the FMS-related tyrosine kinase 3 (Midostaurin is currently the only tyrosine kinase inhibitor (TKI) that has demonstrated superior results compared to standard intensive therapy in younger The oral second-generation bis-aryl urea inhibitor quizartinib is a very selectiveFeasibility of combination therapy with quizartinib and chemotherapy has been shown in several phase II trials [Regarding dosage and schedule, in the first-in-human phase I study, CP0001, quizartinib was administered with intermittent dosing (14 days on drug followed by 14 days rest) from 12 to 450mg and continuous dosing at 200mg and 300mg for 28 days in 76 patients with r/r-AML, regardless of The response rate observed in Study CP0001 was confirmed in the phase II study, AC220-002, of single-agent quizartinib in r/r AML. In this phase II study, a total of 333 patients were enrolled in 2 cohorts; Cohort 1 included patients 60 years or older who were relapsed or refractory to the first line of therapy, and Cohort 2 included patients 18 years or older who were relapsed or refractory to salvage therapy or relapsed after allo-HCT. In Cohort 1, the composite complete remission (CRc) rate was 57% in The maximum tolerated dose (MTD) determined in the phase I study, CP0001, was 200mg continuous daily dosing [The phase IIb 2689-CL-2004 Study was subsequently conducted. A total of 76 patients with Common adverse events (AEs) observed in the phase I and II studies included gastrointestinal disorders (nausea, diarrhea, and vomiting), hematologic disorders (anemia, neutropenia, and thrombocytopenia), febrile neutropenia, fatigue, and QT prolongation.Although hematologic toxicity is associated with the underlying disease, safety reports from Study AC220-002 in AML indicate delayed recovery or continued suppression of absolute neutrophil counts (ANC) and platelets as a consequence of continued treatment with quizartinib [Based on phase I and phase II studies’ results, it appears reasonable and clinically feasible to combine salvage therapy with quizartinib in patients with r/r- The primary objectives of the study are (i) to assess the clinical efficacy of quizartinib in combination with high-dose cytarabine and mitoxantrone and (ii) to assess the clinical efficacy of MRD-triggered and preemptive quizartinib continuation therapy in patients with r/r- 