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CML, Chronic PhasePhase 1NCT05367700

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

A Phase 1 study testing HS-10382(Part 1: Dose escalation) and HS-10382(Part 2: Dose expansion) in people with CML, Chronic Phase and CML, Accelerated Phase, run by Jiangsu Hansoh Pharmaceutical Co., Ltd. at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 74 years
Conditions the study is for
CML, Chronic Phase, CML, Accelerated Phase
What is being tested?
HS-10382(Part 1: Dose escalation) and HS-10382(Part 2: Dose expansion)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
108 participants
Where
1 siteChina
Study dates
28 Apr 2022to 30 Sep 2026
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 74 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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:
Show all 24Show fewer
  • 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
  • Any severe or uncontrolled systemic diseases (i.e. uncontrolled hypertension or diabetes).
  • Clinically severe gastrointestinal dysfunction that may affect drug intake, transport or absorption.
  • Severe infection within 4 weeks prior to the first scheduled dose of HS-10382.
  • History of significant congenital or acquired bleeding disorders unrelated to CML.
  • Inadequate other organ function.
  • History of other malignancies.
  • History of hypersensitivity to any active or inactive ingredient of HS-10382.
  • History of neuropathy or mental disorders, including epilepsy and dementia.
  • 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.

Trial locations and contacts

1 site in 1 country.

Yu Hu contact

13986183871

dr_huyu@126.com

China1 site, 1 recruiting

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

    Wuhan, Hubei, 430022

    Yu Hu, 13986183871, dr_huyu@126.com

    Recruiting

Other trials in China

About this study

Official title: 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.

Read the 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.

Being tested
HS-10382(Part 1: Dose escalation), HS-10382(Part 2: Dose expansion)
Keywords
CML-CP/AP, HS-10382, BCR-ABL TKI, Phase I, Allosteric inhibitor
Medical subject headings
Leukemia, Myeloid, Chronic-Phase, Leukemia, Myeloid, Accelerated Phase

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

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

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

    HS-10382 is administered orally once daily.

Study groups in NCT05367700
Study groupRoleWhat they receive
HS-10382 (Part 1: Dose escalation)ExperimentalThere are five escalation dose cohorts.
Receives: Drug: HS-10382(Part 1: Dose escalation)
HS-10382 (Part 2: Dose expansion)ExperimentalThe recommended dose from the dose-escalation stage and other potential doses will be further explored.
Receives: Drug: HS-10382(Part 2: Dose expansion)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

  2. 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).

    Measured: 6 months

Secondary outcomes (10)

  1. Incidence and severity of treatment-emergent adverse events

    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.

    Measured: From baseline until 28 days after the last dose.

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

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

    Measured: 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.

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

    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.

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

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

    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.

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

  5. Hematologic response

    Hematologic response will be assessed by complete blood count (CBC) and physical examination at each visit.

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

  6. Molecular response

    Molecular response will be assessed by BCR-ABL1 transcript level as measured by RQ-PCR.

    Measured: at screening and 28th day of cycle 3, 6, 9 and 12.

  7. Cytogenetic response

    Cytogenetic response (CyR) is based on the prevalence of Ph+ cells in metaphase from bone marrow (BM) sample.

    Measured: at screening and 28th day of cycle 3, 6, 9 and 12.

  8. Event-free survival (EFS)

    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 .

    Measured: up to 24 months

  9. Progression-free survival (PFS)

    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.

    Measured: up to 24 months

  10. Overall survival (OS)

    OS is defined as the time from the date of first dose to the date of death from any cause.

    Measured: up to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 May 2022
  2. Study start28 Apr 2022
  3. Primary completion30 Dec 2024 (estimated)
  4. Study completion30 Sep 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
108 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05367700
Sponsor's protocol ID
HS-10382-101
Status last verified
Jan 2023
First submitted
6 May 2022
Last updated
13 Jan 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing HS-10382(Part 1: Dose escalation) and HS-10382(Part 2: Dose expansion) in people with CML, Chronic Phase and CML, Accelerated Phase, run by Jiangsu Hansoh Pharmaceutical Co., Ltd. at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 13 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Yu Hu (13986183871, dr_huyu@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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).). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05367700.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2023.

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