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

NCT06530810 | Not Yet Recruiting Phase 1

• 1 other identifier: HS-10382-102
• Study Type: interventional
• Target: 100
• Locations: 0 countries
• Sites: N/A

Brief 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

Conditions

Chronic Myelogenous Leukemia; CML Chronic Phase; CML Accelerated Phase

Keywords

CML-CP/AP; HS-10382; Flumatinib; Allosteric inhibitor

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• Incidence and severity of treatment-emergent adverse events

  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

  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

  Cycle 1 day 1 up to 28 days after the last dose

• half-life (T1/2) of HS-10382 combination therapy

  Cycle 1 day 1 up to 28 days after the last dose

• Area under the curve (AUC) of HS-10382 combination therapy

  Cycle 1 day 1 up to 28 days after the last dose

Study Arms (1)

HS-10382+Flumatinib

EXPERIMENTAL

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)

Drug: HS-10382+Flumatinib

Interventions

HS-10382+Flumatinib DRUG

Drug:HS-10382+Flumatinib HS-10382 is administered orally BID Drug:Flumatinib Flumatinib 400mg once daily

HS-10382+Flumatinib

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Jiangsu Hansoh Pharmaceutical Co., Ltd.: lead

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic-Phase; Leukemia, Myeloid, Accelerated Phase

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Yu Hu, PhD

CONTACT

13986183871; dr_huyu@126.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2024
• First Posted: July 31, 2024
• Study Start: July 31, 2024
• Primary Completion: May 8, 2026
• Study Completion (Estimated): May 8, 2028
• Last Updated: July 31, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share