The purpose of this study is to describe the dose limiting toxicities (DLT) of SKLB1028 when combined with cytarabine/ daunorubicin remission induction in a 7+3 schedule. Safety and tolerability of SKLB1028 will also be evaluated. This study will also characterize the pharmacokinetics (PK) of SKLB1028 when given in combination with cytarabine/daunorubicin remission induction and high-dose cytarabine (HiDAC) consolidation therapy in newly diagnosed acute myeloid leukemia .
Subject has a diagnosis of previously-untreated de novo acute myeloid leukemia (AML) > 20% blasts in the bone marrow according to WHO classification (2016) documented prior to enrollment.;
Age ≥ 18 and < 60 years;
Subjects who are positive for FLT3 mutations by central laboratory;
Subject has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2;
Confirmed diagnosis of acute promyelocytic leukemia (M3 /APL), or BCR-ABL positive leukemia (ie, blast crisis of chronic myelogenous leukemia);
Diagnosis of active malignancy other than AML;
AML secondary to radiotherapy or chemotherapy for other tumors;
AML with central nervous system involvement;
Sequential
SKLB1028 Dose Escalation
DrugDrug :SKLB1028 ;Drug: Cytarabine ;Drug: Daunorubicin
Number of participants with dose limiting toxicities (DLTs)
A DLT is defined as any Grade ≥ 3 non-hematologic or extramedullary toxicity that occur during the DLT assessment period, and that is considered to be possibly, probably, or definitely related to onsolidation therapies including the study drugs.
Pharmacokinetics profile of SKLB1028
Observed trough concentration (Ctrough)
CR rate after the induction therapy
CR is defined as a morphologically leukemia-free state at the post-baseline visit, having a neutrophil count of ≥ 1,000/mm\^3 and platelet count of ≥ 100,000/mm\^3, bone marrow blasts \< 5%. There must be no evidence of Auer rods and no evidence of extramedullary leukemia.
Duration of remission
Duration of remission included duration of composite complete remission (CRc), duration of complete remission (CR)/ complete remission with partial hematologic recovery (CRh), duration of CRh, duration of CR and duration of response (CRc + partial remission (PR).
Overall Survival
OS was measured from the date of the first dose of treatment to the date of death from any cause or to the last date that the patient was known to be alive
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