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

January 12, 2023 updated by: Jiangsu Hansoh Pharmaceutical Co., Ltd.

A Phase I, Open-label, Multicenter Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Efficacy of Single and Multiple Doses of Oral Administration of HS-10382 in Patients With Chronic Myeloid Leukemia.

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is an open-label, multicenter, dose-escalation and expansion, first-in-human study in participants of CML with T315I mutation or without T315I mutation in chronic phase/accelerate phase(CP/AP). This study will consist of two parts: A part 1 dose escalation stage and a part 2 dose expansion stage. The objectives of this study are to evaluate the safety, tolerability, PK and preliminary anti-CML activity, describe the dose-limiting toxicities (DLTs), and determine the maximum tolerated dose (MTD) or maximum applicable dose (MAD) of HS-10382. Participants with CML-CP/AP are eligible for dose escalation study if they had resistance to or unacceptable side effect from BCR-ABL1 TKIs. After determination of the MTD or the MAD for CML patients, dose expansion will be undertaken to further evaluate the efficacy and safety of HS-10382 in patients with CML-CP. All patients will be carefully followed for adverse events during the study treatment and for 28 days after the last dose of study drug. Subjects of this study will be permitted to continue therapy with assessments for progression if the product is well tolerated and the subject has stable disease or better.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
108

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • China
    • Hubei
      • Wuhan, Hubei, China, 430022
        • Recruiting
        • Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 74 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Signed informed consent form.
  2. Men or women aged more than or equal to (≥) 18 years, and less than (<) 75 years.
  3. CML-CP/AP patients with the Ph chromosome or BCR-ABL1 fusion genes.
  4. Patient with CML-CP/AP who are resistant to or intolerant to previous TKIs therapy.
  5. ECOG performance status of 0-2.
  6. Life expectancy ≥ 12 weeks.
  7. 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.
  8. Females must have evidence of non-childbearing potential.

Exclusion Criteria:

  1. CML-CP patients who have acquired CCyR and have not lost it.
  2. Patients with CML-CP who have progressed to AP or blast phase(BP.)
  3. Patients with CML-AP who have obtained CHR or no evidence of CML in peripheral blood.
  4. Patients with CML-AP who have progressed to BP.
  5. Previous treatment with a BCR-ABL1 TKI allosteric inhibitor .

  6. Impaired cardiac function including any one of the following:

    1. 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).
    2. Any clinically important abnormalities in rhythm, conduction, or morphology of the resting ECG.
    3. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events,
    4. Left ventricular ejection fraction (LVEF) ≤ 50%.
    5. During screening period, ECG examination showed average heart rate <50 beats per minute.
    6. Myocardial infarction occurred within 6 months of the first scheduled dose of HS-10382.;
    7. Congestive heart failure occurred within 6 months of the first scheduled dose of HS-10382.;
    8. Uncontrollable angina.
  7. History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis
  8. Any severe or uncontrolled systemic diseases (i.e. uncontrolled hypertension or diabetes).
  9. Clinically severe gastrointestinal dysfunction that may affect drug intake, transport or absorption.
  10. Severe infection within 4 weeks prior to the first scheduled dose of HS-10382.
  11. History of significant congenital or acquired bleeding disorders unrelated to CML.
  12. Inadequate other organ function.
  13. History of other malignancies.
  14. History of hypersensitivity to any active or inactive ingredient of HS-10382.
  15. History of neuropathy or mental disorders, including epilepsy and dementia.
  16. Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: HS-10382 (Part 1: Dose escalation)
There are five escalation dose cohorts.
Drug: HS-10382(Part 1: Dose escalation)
Single or multiple dose(s) of HS-10382 once daily.
Experimental: HS-10382 (Part 2: Dose expansion)
The recommended dose from the dose-escalation stage and other potential doses will be further explored.
Drug: HS-10382(Part 2: Dose expansion)
HS-10382 is administered orally once daily.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Part 1(Dose escalation): Maximum tolerated dose (MTD) for HS-10382
Time Frame: From the single dose to the last dose of the first cycle as 28days of multiple dosing (35days).
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
Time Frame: 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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Incidence and severity of treatment-emergent adverse events
Time Frame: From baseline until 28 days after the last dose.
Assessed by number and severity of adverse events as recorded on the case report form, vital signs, laboratory variables, physical examination, electrocardiogram, and NCI CTCAE v5.0.
From baseline until 28 days after the last dose.
Observed maximum plasma concentration (Cmax) after single dose of HS-10382
Time Frame: 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.
From pre-dose to 120 hours after single dose on Day 1
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
Time Frame: From pre-dose to 120 hours after single dose on Day 1
In the study of single-dose, Tmax will be obtained following administration of a single oral dose of HS-10382 on Day 1 to Day 6.
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
Time Frame: From pre-dose to 120 hours after single dose on Day 1
Area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule.
From pre-dose to 120 hours after single dose on Day 1
Hematologic response
Time Frame: at screening and 28th day of cycle 1,2,3,4,5,6,9 and 12.
Hematologic response will be assessed by complete blood count (CBC) and physical examination at each visit.
at screening and 28th day of cycle 1,2,3,4,5,6,9 and 12.
Molecular response
Time Frame: at screening and 28th day of cycle 3, 6, 9 and 12.
Molecular response will be assessed by BCR-ABL1 transcript level as measured by RQ-PCR.
at screening and 28th day of cycle 3, 6, 9 and 12.
Cytogenetic response
Time Frame: at screening and 28th day of cycle 3, 6, 9 and 12.
Cytogenetic response (CyR) is based on the prevalence of Ph+ cells in metaphase from bone marrow (BM) sample.
at screening and 28th day of cycle 3, 6, 9 and 12.
Event-free survival (EFS)
Time Frame: up to 24 months
EFS is defined as the time from the date of first dose to the earliest occurrence of the following events: death due to any cause ; loss of CHR ,loss of PCyR ;loss of CCyR ; discontinuation of study treatment due to AE or treatment failure ; progression to AP/BC .
up to 24 months
Progression-free survival (PFS)
Time Frame: up to 24 months
PFS is defined as the time from the date of first dose to the earliest occurrence of progression to AP/BC or death from any cause.
up to 24 months
Overall survival (OS)
Time Frame: up to 24 months
OS is defined as the time from the date of first dose to the date of death from any cause.
up to 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Jiangsu Hansoh Pharmaceutical Co., Ltd.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: yu Hu, Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 28, 2022

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 30, 2024

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 30, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 6, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 6, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 10, 2022

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 13, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 12, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • HS-10382-101

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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