Efficacy endpoints
absence of extramedullary disease, death, neutropenia, Leukemia, HAM, thrombocytopenia, extramedullary disease, leukemic blasts, extramedullary leukemia
RECURRENCE, LEUKEMIA, NEUTROPENIA, DISEASE, THROMBOCYTOPENIA, EVENT, SECONDARY, EVENTS, RELAPSE
The primary endpoint of the study is the achievement of CR, Cri, or CRh after salvage therapy with HAM in combination with quizartinib. CR is defined as bone marrow blasts <5%, absence of circulating blasts and blasts with Auer rods, absence of extramedullary disease, neutrophil count ≥1000/μl, and platelet count ≥100,000/μl. CRi is defined as CR with residual neutropenia (neutrophils < 1000/μl) or thrombocytopenia (platelets < 100 000/μl) and CRh is defined as a CR with partial recovery of peripheral blood counts with residual neutropenia (neutrophils < 500/μl) or thrombocytopenia (platelets < 50,000/μl).Refractory disease or treatment failure is defined as failure to achieve CR, Cri, or CRh, presence of Auer rods, or appearance of new or worsening extramedullary disease after one course of intensive treatment. Relapse after CR, CRi, or CRh is characterized by ≥5% blasts in the bone marrow aspirate and/or biopsy not attributable to any other cause, the reappearance of leukemic blasts in the peripheral blood, the new appearance of extramedullary leukemia, or presence of Auer rods. Platelet and neutrophil counts for the assessments of CR, CRi, and CRh are delineated based on the 2017 recommendations from the International Working Group commissioned by the European Leukemia Net [Secondary survival endpoints are event-free survival (EFS), defined from randomization until one of the following events, whichever occurs first: (a) failure to obtain CR or CRi or CRh after Q-HAM therapy, (b) relapse from CR/Cri/CRh, or (c) death from any cause. Patients without an event are censored at the last follow-up. Overall survival (OS) is defined as the time from randomization until death from any cause and relapse-free survival (RFS) is measured from the first CR/Cri/CRh to the time of recurrence of the disease or death from any cause, whichever occurs first. Patients without event are censored at the last date of follow-up. Cumulative incidence of relapse (CIR) is defined as the time from the achievement of a CR/CRi/CRh after salvage therapy to the recurrence of the disease, whereby death from any cause is a competing event. Cumulative incidence of death (CID) is defined as the time from the achievement of a CR/CRi/CRh after salvage therapy to death from any cause whereby recurrence of the disease is a competing event.Further secondary endpoints are patient-reported outcomes (PROs). PROs include assessments of (a) health-related quality of life (QoL), calculated as the EORTC QLQ-C30 Summary Score [