Clinical trial · Interventional
Study of HS-10382 Combination in Patients With Chronic Myeloid Leukemia (CML)
A Phase 1b, Open-label, Multi-center Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of HS-10382 Combination Therapy in Patients With Chronic Myeloid Leukemia
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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. Flumatinib is the first approved second generation TKI in China and a derivative of imatinib. The primary objective of this study is to evaluation the safety and tolerability and of HS-10382 combination therapy in patients with chronic myeloid leukemia (CML). The secondary objectives is to evaluate the PK profile, major metabolites and efficacy of HS-10382 in CML-CP/AP subjects after combination therapy, and to explore the kinase domain mutations associated with TKI resistance
Conditions
Conditions (3)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Chronic Myelogenous Leukemia | Myeloid Leukemia | CURATED_BROADER | 0.80 |
| CML Accelerated Phase | — | UNRESOLVED | — |
| CML Chronic Phase | — | UNRESOLVED | — |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| HS-10382+Flumatinib | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- HS-10382+Flumatinib
- description
- Subjects with resistant or intolerant CML CP/AP will be enrolled in dose-escalation stage.Dose escalation of HS-10382 combined flumatinib will be done to determine maximum tolerated dose(Part 1). Depending on data obtained from the dose-escalation stage,dose expansion may proceed with in subjects with newly diagnosed CML-CP.The safety and efficacy will be evaluated at the target dose.(Part 2)
- interventionNames
- Drug: HS-10382+Flumatinib
Primary outcomes (1)
- measure
- Maximum tolerated dose (MTD) for HS-10382 combined treatment
- timeFrame
- Up to day 28 from the first dose
- description
- MTD was defined as the previous dose level at which 2 out of 3 subjects or 2 out of 6 subjects experienced a DLT
Secondary outcomes (11)
- measure
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
- Maximum age
- 75 Years
Show eligibility criteria text
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 0-1 and no worsening within 2 weeks before the first dose. * 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 . * 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%. * Myocardial infarction occurred within 6 months of the first scheduled dose of study drug.; * Congestive heart failure occurred within 6 months of the first scheduled dose of study drug.; * 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 study drug * Inadequate other organ function. * History of other malignancies. * History of hypersensitivity to any active or inactive ingredient of HS-10382 and flumatinib. * 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
References
Publications (0)
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