Clinical trial NCT05445154: SKLB1028, Daunorubicin, and Cytarabine in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Newly Diagnosed Acute Myeloid Leukemia (AML)
Lead sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-07-06
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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 .


Eligibility criteria: Inclusion Criteria:

1. 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.;
2. Age ≥ 18 and \< 60 years;
3. Subjects who are positive for FLT3 mutations by central laboratory;
4. Subject has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2;
5. Subject must meet the following criteria as indicated on the clinical laboratory tests;

   1. Serum aspartate aminotransf
   2. Total serum bilirubin ≤ 2.5 x institutional ULN
   3. Serum creatinine ≤ 3 x institutional ULN or an estimated glomerular filtration rate (eGFR) of \> 30 ml/min
6. Subject is suitable for oral administration of study drug.

Exclusion Criteria:

1. Confirmed diagnosis of acute promyelocytic leukemia (M3 /APL), or BCR-ABL positive leukemia (ie, blast crisis of chronic myelogenous leukemia);
2. Diagnosis of active malignancy other than AML;
3. AML secondary to radiotherapy or chemotherapy for other tumors;
4. AML with central nervous system involvement;
5. Refractory hypokalemia or hypomagnesemia that is not easily corrected by symptomatic treatment and that occurs repeatedly in the past;
6. Current clinically significant graft-ve
7. Previous history of other malignancies.
8. Patients with clinically significant coagulation abnormalities, such as disseminated intravascular coagulation (DIC), hemophilia A, hemophilia B, and von Willebrand disease;
9. 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
10. 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;

Primary outcomes:
measure: Number of participants with dose limiting toxicities (DLTs)
timeFrame: up to Day42
Secondary outcomes:
measure: Pharmacokinetics profile of SKLB1028
timeFrame: Days 8, 15, 18, and 21 for remission induction and Days 8, and 21 for consolidation and Days 1 for maintenance
measure: CR rate after the induction therapy
timeFrame: up to 3months
measure: Duration of remission
timeFrame: up to 24months
measure: Overall Survival
timeFrame: up to 60months
measure: Event-Free Survival
timeFrame: up to 24months
measure: Leukemia-free survival
timeFrame: up to 24months
measure: Rate of hematopoietic stem cell transplantation
timeFrame: up to 12months
Other outcomes:
Locations:
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
Study officials:
References: