A Single-Arm, Multicenter, Open-Label, Dose- Escalating and Expanding,Phase I/II Study of SKLB1028 Combined With "7+3" Standard Chemotherapy in Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 58
- 试验地点
- 1
- 主要终点
- Number of participants with dose limiting toxicities (DLTs)
研究概览
简要总结
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 .
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 59 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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;
- •Subject must meet the following criteria as indicated on the clinical laboratory tests;
- •Serum aspartate aminotransf
- •Total serum bilirubin ≤ 2.5 x institutional ULN
- •Serum creatinine ≤ 3 x institutional ULN or an estimated glomerular filtration rate (eGFR) of > 30 ml/min
- •Subject is suitable for oral administration of study drug.
排除标准
- •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;
- •Refractory hypokalemia or hypomagnesemia that is not easily corrected by symptomatic treatment and that occurs repeatedly in the past;
- •Current clinically significant graft-ve
- •Previous history of other malignancies.
- •Patients with clinically significant coagulation abnormalities, such as disseminated intravascular coagulation (DIC), hemophilia A, hemophilia B, and von Willebrand disease;
- •Major surgery of major organs has been performed before entering the study (for the definition of major surgery, refer to Grade 3 and 4 surgery specified in Management Measures for Clinical Application of Medical Technology, or the patient has not yet fully recovered from
- •Subject has received prior therapy for AML with the following exceptions: a. emergency leukapheresis; b. emergency treatment with hydroxyurea ;c. growth factor or cytokine support; d. steroid for anaphylaxis or transfusion reaction;
研究组 & 干预措施
SKLB1028 Dose Escalation
Part1:Patients will receive a standard combination of chemotherapy drugs during remission induction therapy that includes cytarabine, daunorubicin, and the experimental drug SKLB1028.SKLB1028 capsules beginning at 100 mg bid.
Part2: Once the appropriate therapeutic schedule has been established in Part 1, up to 20 subjects will be enrolled into an expansion cohort.
干预措施: SKLB1028 Dose Escalation (Drug)
结局指标
主要结局
Number of participants with dose limiting toxicities (DLTs)
时间窗: up to Day42
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.
次要结局
- Pharmacokinetics profile of SKLB1028(Days 8, 15, 18, and 21 for remission induction and Days 8, and 21 for consolidation and Days 1 for maintenance)
- CR rate after the induction therapy(up to 3months)
- Duration of remission(up to 24months)
- Overall Survival(up to 60months)
- Event-Free Survival(up to 24months)
- Leukemia-free survival(up to 24months)
- Rate of hematopoietic stem cell transplantation(up to 12months)