A Study of HS-10382 in Patients With Chronic Myeloid Leukemia.
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-74
SponsorJiangsu Hansoh Pharmaceutical Co., Ltd.
About this trial
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. The purpose of this study is to investigate the safety/tolerability and the pharmacokinetic(PK) profile of HS-10382 in patients with chronic myeloid leukemia (CML). Anti-CML activity will also be investigated in this study.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial design
Design model
Sequential
Treatments tested in this trial
HS-10382(Part 1: Dose escalation)
DrugSingle or multiple dose(s) of HS-10382 once daily.
HS-10382(Part 2: Dose expansion)
DrugHS-10382 is administered orally once daily.
Treatment groups
108 Participants
are divided into 2 treatment groupsGroup A: HS-10382 (Part 1: Dose escalation)Experimental treatment 1 intervention
Group B: HS-10382 (Part 2: Dose expansion)Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Part 1(Dose escalation): Maximum tolerated dose (MTD) for HS-10382
MTD was defined as the previous dose level at which 2 out of 3 subjects or 2 out of 6 subjects experienced a DLT.
Time frame
From the single dose to the last dose of the first cycle as 28days of multiple dosing (35days).2
Part 2(Dose expansion): Major cytogenetic response (MCyR) rate at 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).
Time frame
6 monthsSecondary outcomes
1
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.
Time frame
From baseline until 28 days after the last dose.2
Observed maximum plasma concentration (Cmax) after single dose of HS-10382
From pre-dose to 120 hours after single dose on Day 1
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 6.3
Time to reach maximum plasma concentration (Tmax) after single dose of HS-10382
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.
Time frame
From pre-dose to 120 hours after single dose on Day 14
Area under plasma concentration versus time curve from zero to last sampling time (AUC0-t) after single dose of HS-10382
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.
Time frame
From pre-dose to 120 hours after single dose on Day 1Sponsors and contacts
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Source ClinicalTrials.gov