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

NCT05947344 | Recruiting Phase 1

• 1 other identifier: FLT3-AML-101CN
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

AML, Adult

Keywords

FLT3 inhibitor

Outcome Measures

Primary Outcomes (1)

• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0.

  Assessing the incidence of adverse events (AEs) using the Common Terminology Criteria for Adverse Events (CTCAE Version 5)

  Up to 3 years.

Secondary Outcomes (12)

• Assessment of the AUC of STI-8591 and its major metabolites (if any).

  At the end of Cycle 1 and the first day of Cycle 2 (each cycle is 30 days) .

• Assessment of the Tmax of STI-8591 and its major metabolites (if any).

  At the end of Cycle 1 and the first day of Cycle 2 (each cycle is 30 days) .

• Assessment of the Cmax of STI-8591 and its major metabolites (if any).

  At the end of Cycle 1 and the first day of Cycle 2 (each cycle is 30 days) .

• Percentage change in FLT3 plasma inhibitory activity (PIA) relative to baseline

  At the end of Cycle 1 and the first day of Cycle 2 (each cycle is 30 days) .

• Assessing the CRc of STI-8591 in advanced AML.

  Through study completion, an average of 2 years.

Study Arms (1)

STI-8591 in Advanced Acute Myeloid Leukemia (AML)

EXPERIMENTAL

Subjects with Advanced primary AML or MDS secondary to AML or AML-MR.

Drug: STI-8591

Interventions

STI-8591 DRUG

Four dosing cohorts will be evaluated in the dose escalation phase: 20mg, 40mg, 60mg and 80mg. Expansion is planned in two dose groups of 40mg and 60mg.

Also known as: STI-8591 alone

STI-8591 in Advanced Acute Myeloid Leukemia (AML)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntary signing of ICF.
• Age ≥ 18 years old.
• Expected survival \>12 weeks.
• ECOG scores physical fitness status 0 to 2.
• Subjects are willing to undergo a bone marrow aspiration/biopsy as required by the protocol, which is used to assess the subject's response to treatment.
• Laboratory test index requirements within 7 days prior to the first dose, including:
• White blood cell count (WBC) ≤ 20 x 109 /L \[(hydroxyurea is allowed up to the first dose to stabilize the WBC count up to a maximum dose of 5 g/day. Hydroxyurea may be continued for up to 28 days after the first dose (i.e., the first dosing cycle) at the discretion of the investigator, but generally not beyond 28 days)\].
• Alanine aminotransferase (ALT) ≤ 2.5 x ULN (≤ 5 x ULN if liver involvement is known).
• Aspartate aminotransferase (AST) ≤ 2.5 x ULN (≤ 5 x ULN if liver involvement is known) Total bilirubin (TBIL) ≤ 1.5 x ULN (\< 3.0 x ULN if diagnosed with Gilbert's syndrome) Estimated glomerular filtration rate (eGFR, calculated according to the Cockcroft-Gault formula or by measuring 24-hour urine) \> 50 mL/min.
• Be willing and able to comply with the study schedule and all other study protocol requirements.
• Women of childbearing potential (WOCBP) (women of childless potential defined as sexually mature women who have undergone hysterectomy or bilateral oophorectomy or bilateral salpingo-oophorectomy or bilateral tubal ligation/closure, or who are unable to have children because of congenital or acquired disease or who have been spontaneously menopausal for ≥12 months) must have a negative blood pregnancy test performed during screening.
• Female subjects of childbearing potential and male subjects whose partners are of childbearing potential must use a highly effective method of contraception from the time of screening until 180 days after the last treatment.
• Subjects are required to provide FLT3 mutation status testing within 6 months prior to the first dose, and if not, are willing to undergo screening period testing as required by the protocol.

You may not qualify if:

• Known hypersensitivity to any component of the study drug formulation.
• Subjects were diagnosed with acute promyelocytic leukemia (APL).
• Subjects have BCR-ABL positive leukemia (chronic myelogenous leukemia acute).
• Subjects developed secondary AML after previous antitumor therapy for other tumors (except MDS, MDS/MPN).
• Subjects had CNS leukemia with associated clinical symptoms.
• Enrolled in any therapeutic clinical study within 28 days prior to the first dose and enrolled in treatment, except in the survival follow-up phase of the interventional study.
• Received anti-tumor therapy (including chemotherapy, immunotherapy, endocrine therapy, targeted therapy, etc.) within 28 days or 5 half-lives (whichever is shorter) prior to the first dose. Received radiotherapy within 14 days prior to the first dose. Palliative radiotherapy for symptom control is allowed to be completed at least 7 days prior to the first dose. Have received herbal therapy with approved indications for antitumor use within 7 days prior to the first dose.
• ≥ Grade 2 graft-versus-host disease (GvHD), including acute, chronic or overlapping or escalating GvHD therapy within 14 days prior to first dose or being treated with systemic cortisol hormone for GvHD.
• Received chimeric antigen receptor T-cell immunotherapy (CAR-T) within 3 months prior to the first dose.
• Strong inducer or strong inhibitor of cytochrome P450 (CYP450) 2C8 or 3A4 enzymes taken within 14 days prior to the first dose, unless the investigator assesses that the drug is necessary for the subject's treatment regimen.
• Major surgery within 28 days prior to first dose or minor surgery within 7 days prior to first dose, except diagnostic biopsy, insertion of vascular access device
• Subjects have clinically significant coagulation abnormalities, such as disseminated intravascular coagulation (DIC), hemophilia A, hemophilia B, and vascular hemophilia.
• Intractable hypokalemia or hypomagnesemia that is not easily corrected by symptomatic treatment and with previous recurrent episodes.
• Active tuberculosis, or interstitial lung disease requiring corticosteroid therapy, drug-induced interstitial lung disease, history of radiation pneumonia, or clinically active interstitial lung disease as suggested by any current evidence, prior to the first dose.
• Presence of an uncontrolled active infection (defined as exhibiting persistent signs/symptoms associated with the infection that do not improve despite appropriate antibiotic or other treatment) within 72 hours prior to the first dose. Ongoing use of prophylactic antibiotics, antifungals, or antivirals is eligible for enrollment.

Sponsors & Collaborators

• Zhejiang ACEA Pharmaceutical Co. Ltd.: lead

Study Sites (1)

the First Affiliated Hospital, College of Medicine, Zhejiang University

Hangzhou, Zhejiang, China

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Central Study Contacts

Jie Jin, Doctor

CONTACT

0571-87236896; jiej0503@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2023
• First Posted: July 17, 2023
• Study Start: December 8, 2023
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: March 17, 2025

Record last verified: 2025-03

Locations

CN (1)