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

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)

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 .

Study Overview

• Status: Recruiting
• Conditions: Newly Diagnosed Acute Myeloid Leukemia (AML)
• Intervention / Treatment: Drug: SKLB1028 Dose Escalation

• Study Type: Interventional
• Enrollment (Anticipated): 58
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Liu Ting, Chief doctor; Phone Number: +8618980601240; Email: liuting@scu.edu.cn
• Study Contact Backup: Name: Wang Jianxiang, Chief doctor; Email: wangjx@ihcams.ac.cn

Study Locations

• China
  • Chengdu, China
    • Recruiting
    • West China Hospital of Sichuan University
    • Contact: Liu Ting, Chief doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 59 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Drug: SKLB1028 Dose Escalation; Drug :SKLB1028 ;Drug: Cytarabine ;Drug: Daunorubicin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	up to Day42

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics profile of SKLB1028	Observed trough concentration (Ctrough)	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	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.	up to 3months
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).	up to 24months
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	up to 60months
Event-Free Survival	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.	up to 24months
Leukemia-free survival	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).	up to 24months
Rate of hematopoietic stem cell transplantation	Transplantation rate is defined as the percentage of participants undergoing hematopoietic stem cell transplant (HSCT).	up to 12months

Collaborators and Investigators

• Sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2021
• Primary Completion (Anticipated): October 31, 2024
• Study Completion (Anticipated): December 31, 2026

Study Registration Dates

• First Submitted: June 4, 2021
• First Submitted That Met QC Criteria: June 30, 2022
• First Posted (Actual): July 6, 2022

Study Record Updates

• Last Update Posted (Actual): July 6, 2022
• Last Update Submitted That Met QC Criteria: June 30, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: HA114-CSP-007

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No