SKLB1028, Daunorubicin, and Cytarabine in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)

Phase 1

Recruiting

• Conditions: Newly Diagnosed Acute Myeloid Leukemia (AML)
• Interventions: Drug: SKLB1028 Dose Escalation

• Registration Number: NCT05445154
• Lead Sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.

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 .

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-06-04
• Study Start: 2021-08-31
• Status Verified: 2022-05
• Study First Submitted QC: 2022-06-30
• Last Update Submitted: 2022-06-30
• Study First Posted: 2022-07-06
• Last Update Posted: 2022-07-06
• Primary Completion: 2024-10-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 58

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;

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
SKLB1028 Dose Escalation	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.

Primary Outcome Measures

Name	Time	Method
Number of participants with dose limiting toxicities (DLTs)	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.

Secondary Outcome Measures

Name	Time	Method
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	Observed trough concentration (Ctrough)
CR rate after the induction therapy	up to 3months	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	up to 24months	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	up to 60months	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
Event-Free Survival	up to 24months	EFS was defined as the time from randomization until treatment failure (Composite complete remission (CRc) or partial remission (PR) were not reached within 4 cycles), relapse (excluding relapse after PR), or death from any cause, whichever occurs first.
Leukemia-free survival	up to 24months	The LFS was defined as the time from the date of first CR until the date of documented relapse (excluding relapse from PR) or death for participants who achieved CR (relapse date or death date - first CR disease assessment date + 1).
Rate of hematopoietic stem cell transplantation	up to 12months	Transplantation rate is defined as the percentage of participants undergoing hematopoietic stem cell transplant (HSCT).

Trial Locations

Locations (1)

West China Hospital of Sichuan University; 🇨🇳 Chengdu, China