Study of HS-10382 Combination in Patients With Chronic Myeloid Leukemia (CML)

Trial Title: Study of HS-10382 Combination in Patients With Chronic Myeloid Leukemia (CML)

NCT ID: NCT06530810

Condition: Chronic Myelogenous Leukemia
CML Chronic Phase
CML Accelerated Phase

Conditions: Official terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Flumatinib

Conditions: Keywords:
CML-CP/AP
HS-10382
Flumatinib
Allosteric inhibitor

Study type: Interventional

Study phase: Phase 1

Overall status: Not yet recruiting

Study design:

Allocation: N/A

Intervention model: Sequential Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: HS-10382+Flumatinib
Description: Drug:HS-10382+Flumatinib HS-10382 is administered orally BID Drug:Flumatinib Flumatinib 400mg once daily
Arm group label: HS-10382+Flumatinib

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. 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

Criteria for eligibility:
Criteria:
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

Gender: All

Minimum age: 18 Years

Maximum age: 75 Years

Healthy volunteers: No

Start date: July 31, 2024

Completion date: May 8, 2028

Lead sponsor:
Agency: Jiangsu Hansoh Pharmaceutical Co., Ltd.
Agency class: Industry

Source: Jiangsu Hansoh Pharmaceutical Co., Ltd.

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06530810