A Study of HS-10382 in Patients With Chronic Myeloid Leukemia.
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ClinicalTrials.gov Identifier: NCT05367700 |
Recruitment Status :
Recruiting
First Posted : May 10, 2022
Last Update Posted : January 13, 2023
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Condition or disease | Intervention/treatment | Phase |
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CML, Chronic Phase CML, Accelerated Phase | Drug: HS-10382(Part 1: Dose escalation) Drug: HS-10382(Part 2: Dose expansion) | Phase 1 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 108 participants |
Allocation: | Non-Randomized |
Intervention Model: | Sequential Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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. |
Actual Study Start Date : | April 28, 2022 |
Estimated Primary Completion Date : | December 30, 2024 |
Estimated Study Completion Date : | September 30, 2026 |
Arm | Intervention/treatment |
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Experimental: HS-10382 (Part 1: Dose escalation)
There are five escalation dose cohorts.
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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.
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Drug: HS-10382(Part 2: Dose expansion)
HS-10382 is administered orally once daily. |
- 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.
- 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).
- 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.
- 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
- 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.
- 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.
- 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.
- 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.
- 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.
- 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 .
- 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.
- 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.
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Ages Eligible for Study: | 18 Years to 74 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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 .
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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
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05367700
Contact: Yu Hu | 13986183871 | dr_huyu@126.com |
China, Hubei | |
Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology | Recruiting |
Wuhan, Hubei, China, 430022 | |
Contact: Yu Hu 13986183871 dr_huyu@126.com |
Principal Investigator: | Yu Hu | Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology |
Responsible Party: | Jiangsu Hansoh Pharmaceutical Co., Ltd. |
ClinicalTrials.gov Identifier: | NCT05367700 |
Other Study ID Numbers: |
HS-10382-101 |
First Posted: | May 10, 2022 Key Record Dates |
Last Update Posted: | January 13, 2023 |
Last Verified: | January 2023 |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
CML-CP/AP HS-10382 BCR-ABL TKI Phase I Allosteric inhibitor |
Leukemia, Myelogenous, Chronic, BCR-ABL Positive Leukemia, Myeloid, Chronic-Phase Leukemia, Myeloid, Accelerated Phase Leukemia Neoplasms by Histologic Type Neoplasms Hematologic Diseases |
Leukemia, Myeloid Myeloproliferative Disorders Bone Marrow Diseases Chronic Disease Disease Attributes Pathologic Processes |