Study of HS-10382 Combination in Patients With Chronic Myeloid Leukemia (CML)
NCT Number: NCT06530810
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: Chronic Myelogenous Leukemia|CML Chronic Phase|CML Accelerated Phase
Interventions: DRUG: HS-10382+Flumatinib
Sponsor: Jiangsu Hansoh Pharmaceutical Co., Ltd.
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 100
Study Design: Allocation: NA|Intervention Model: SEQUENTIAL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-07-31
Completion Date: 2028-05-08

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

Primary Outcome Measures: Maximum tolerated dose (MTD) for HS-10382 combined treatment, MTD was defined as the previous dose level at which 2 out of 3 subjects or 2 out of 6 subjects experienced a DLT, Up to day 28 from the first dose
Secondary Outcome Measures: 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, Cycle 1 day 1 up to 28 days after the last dose|maximum plasma concentration of HS-10382 or Flumatinib(and its major metabolite ) after HS-10382 combination therapy, Cmax is the maximum observed concentration., Cycle 1 day 1 up to 28 days after the last dose|Time to reach maximum plasma concentration of HS-10382 or Flumatinib(and its major metabolite) after HS-10382 combination therapy, Tmax is defined as time to reach maximum observed plasma concentration, Cycle 1 day 1 up to 28 days after the last dose|half-life (T1/2) of HS-10382 combination therapy, half-life is the time measured for the concentration to decrease by one half, Cycle 1 day 1 up to 28 days after the last dose|Area under the curve (AUC) of HS-10382 combination therapy, The AUC is defined as the area under the plasma concentration-time curve, Cycle 1 day 1 up to 28 days after the last dose|Hematologic Response of combination therapy with HS-10382, To record and analyse the hematologic response of subjects. Hematologic response will be assessed by complete blood count (CBC) and physical examination at each visit., up to 24 months|Cytogenetic Response of combination therapy with HS-10382, To record and analyse the cytogenetic response of subjects. Cytogenetic response (CyR) is based on the prevalence of Ph+ cells in metaphase from bone marrow (BM) sample., up to 24 months|Molecular Response of combination therapy with HS-10382, To record and analyse the molecular response of subjects. Molecular response will be assessed by BCR-ABL1 transcript level as measured by RQ-PCR., up to 24 months|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 ., up to 24 months|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., From the first dose to disease progression or withdrawal from study, whichever came first,up to 24 months|Overall survival (OS), OS is defined as the time from the date of first dose to the date of death from any cause., From the first dose up to death or withdrawal from study, whichever came first, up to 24 months