A Study to Evaluate the STI-8591 in Subjects With Advanced Acute Myeloid Leukemia (AML)

AML, Adult Clinical Trial

Official title: A Multicenter, Open, Dose Escalation and Dose Expansion Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of STI-8591 in Subjects With Advanced Acute Myeloid Leukemia (AML)

Status Recruiting

Clinical Trial Summary

This is a first-in-human, dose-escalation and dose-expansion Phase I study to evaluate the safety, tolerability, pharmacokinetics (PK) and efficacy of STI-8591 in subjects with advanced AML who have signed an informed consent form (ICF) and have been screened for enrollment in this study.

• Dose escalation phase: rapid titration and conventional 3+3 test design were used to evaluate the safety, dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and PK characteristics of STI-8591.

• Dose Expansion Phase: Evaluate the safety, preliminary efficacy and determine the recommended phase II dose (RP2D) of STI-8591 for the treatment of subjects with advanced AML under the conditions of reaching the expanded dose.

Clinical Trial Description

Dose escalation phase:Based on the preclinical trial data and with reference to the modified Fibonacci method, the dose escalation ratios are 100%, 100%, 50% and 6.7%, and the initial 5 dose groups for STI-8591 dose escalation are 40, 80, 160, 240 and 280 mg/day, respectively. Screened subjects will be entered into the 5 dose groups in order of succession from lowest to highest dose.This test dose increment will be performed using the rapid titration method and the traditional 3+3 test design.

Dose expansion phase:During dose escalation, for dose groups (except for ≥2 DLT dose groups) when the following dose signals suggesting initial efficacy are present.

1) CR, CRh or CRi in ≥1 subject in either dose group.2) Median decrease in FLT3 phosphorylation was ≥90% in ≥3 subjects in either dose group.The SRC will decide whether to initiate an extension study for that dose group and its subsequent dose groups at the same time as the dose escalation to the next dose group. Subjects in the dose escalation phase will be administered BID every 28 days in 1 cycle, with ≥8h between doses, fasting for at least 2 hours before and at least 1 hour after dosing with approximately 240mL of water (subject to adjustment based on data results from the dose escalation phase) . If initiation was determined, the dose group identified for initiation and its subsequent dose group extension studies were further enrolled in 14 to 17 cases [a total of 20 cases in each dose group, with FLT3 mutation-positive (FLT3 internal tandem repeat (ITD) and/or FLT3 tyrosine kinase structural domain (TKD) mutation-positive subjects enrolled in at least 10 cases] to further define the final RP2D. ;

Related Conditions & MeSH terms

• AML, Adult
• Leukemia, Myeloid, Acute

• NCT number: NCT05947344
• Study type: Interventional
• Source: Zhejiang ACEA Pharmaceutical Co. Ltd.
• Contact: Jie Jin, Doctor
• Phone: 0571-87236896
• Email: jiej0503@163.com
• Status: Recruiting
• Phase: Phase 1
• Start date: December 8, 2023
• Completion date: July 2025