A Study of HS-10382 in Patients With Chronic Myeloid Leukemia.

NCT05367700 | Recruiting Phase 1

• 1 other identifier: HS-10382-101
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

Brief Summary

HS-10382 is a small molecular, oral potent, allosteric inhibitor. By binding a myristoyl site of the BCR-ABL1 protein, HS-10382 locks BCR-ABL1 into an inactive conformation. The purpose of this study is to investigate the safety/tolerability and the pharmacokinetic(PK) profile of HS-10382 in patients with chronic myeloid leukemia (CML). Anti-CML activity will also be investigated in this study.

Conditions

CML, Chronic Phase; CML, Accelerated Phase

Keywords

CML-CP/AP; HS-10382; BCR-ABL TKI; Phase I; Allosteric inhibitor

Outcome Measures

Primary Outcomes (2)

• Part 1(Dose escalation): Maximum tolerated dose (MTD) for HS-10382

  MTD was defined as the previous dose level at which 2 out of 3 subjects or 2 out of 6 subjects experienced a DLT.

  From the single dose to the last dose of the first cycle as 28days of multiple dosing (35days).

• Part 2(Dose expansion): Major cytogenetic response (MCyR) rate at 6 months

  MCyR is the proportion of patients achieving Complete cytogenetic response (CCyR: defined as 0% Philadelphia chromosome-positive \[Ph+\] metaphases by cytogenetic analysis of bone marrow) and Partial Cytogenetic Response (PCyR: defined as \>0% to 35% Ph+ metaphases by cytogenetic analysis of bone marrow).

  6 months

Secondary Outcomes (10)

• Incidence and severity of treatment-emergent adverse events

  From baseline until 28 days after the last dose.

• Observed maximum plasma concentration (Cmax) after single dose of HS-10382

  In the study of single-dose, Cmax will be obtained following administration of a single oral dose of HS-10382 on Day 1 to Day 6.

• Time to reach maximum plasma concentration (Tmax) after single dose of HS-10382

  From pre-dose to 120 hours after single dose on Day 1

• Area under plasma concentration versus time curve from zero to last sampling time (AUC0-t) after single dose of HS-10382

  From pre-dose to 120 hours after single dose on Day 1

• Hematologic response

  at screening and 28th day of cycle 1,2,3,4,5,6,9 and 12.

Study Arms (2)

HS-10382 (Part 1: Dose escalation)

EXPERIMENTAL

There are five escalation dose cohorts.

Drug: HS-10382(Part 1: Dose escalation)

HS-10382 (Part 2: Dose expansion)

EXPERIMENTAL

The recommended dose from the dose-escalation stage and other potential doses will be further explored.

Drug: HS-10382(Part 2: Dose expansion)

Interventions

HS-10382(Part 1: Dose escalation) DRUG

Single or multiple dose(s) of HS-10382 once daily.

HS-10382 (Part 1: Dose escalation)

HS-10382(Part 2: Dose expansion) DRUG

HS-10382 is administered orally once daily.

HS-10382 (Part 2: Dose expansion)

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent form.
• Men or women aged more than or equal to (≥) 18 years, and less than (\<) 75 years.
• CML-CP/AP patients with the Ph chromosome or BCR-ABL1 fusion genes.
• Patient with CML-CP/AP who are resistant to or intolerant to previous TKIs therapy.
• ECOG performance status of 0-2.
• Life expectancy ≥ 12 weeks.
• Men or women should be using adequate contraceptive measures throughout the study; Females should not be breastfeeding at the time of screening, during the study and until 6 months after completion of the study.
• Females must have evidence of non-childbearing potential.

You may not qualify if:

• CML-CP patients who have acquired CCyR and have not lost it.
• Patients with CML-CP who have progressed to AP or blast phase(BP.)
• Patients with CML-AP who have obtained CHR or no evidence of CML in peripheral blood.
• Patients with CML-AP who have progressed to BP.
• Previous treatment with a BCR-ABL1 TKI allosteric inhibitor .
• Impaired cardiac function including any one of the following:
• Resting corrected QT interval (QTc) \> 470 ms obtained from electrocardiogram (ECG), using the screening clinic's ECG machine and Fridericia's formula for QT interval correction (QTcF).
• Any clinically important abnormalities in rhythm, conduction, or morphology of the resting ECG.
• Any factors that increase the risk of QTc prolongation or risk of arrhythmic events,
• Left ventricular ejection fraction (LVEF) ≤ 50%.
• During screening period, ECG examination showed average heart rate \<50 beats per minute.
• Myocardial infarction occurred within 6 months of the first scheduled dose of HS-10382.;
• Congestive heart failure occurred within 6 months of the first scheduled dose of HS-10382.;
• Uncontrollable angina.
• History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis

Sponsors & Collaborators

• Jiangsu Hansoh Pharmaceutical Co., Ltd.: lead

Study Sites (1)

Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Chronic-Phase; Leukemia, Myeloid, Accelerated Phase

Condition Hierarchy (Ancestors)

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Yu Hu

  Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yu Hu

CONTACT

13986183871; dr_huyu@126.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2022
• First Posted: May 10, 2022
• Study Start: April 28, 2022
• Primary Completion: December 30, 2024
• Study Completion (Estimated): September 30, 2026
• Last Updated: January 13, 2023

Record last verified: 2023-01

Locations

CN (1)