Tolerance and Pharmacokinetics of SHR1459 in Patients With Recurrent Replased/Refractory Mature B Cell Neoplasmstumor
- Registration Number
- NCT03664297
- Lead Sponsor
- Jiangsu HengRui Medicine Co., Ltd.
- Brief Summary
SHR1459 is a selective small molecule BTK inhibitor developed by Jiangsu Hengrui medicine Limited, by inhibiting the phosphorylation of BTK and down regulation of BCR signal transduction pathway, And then selectively inhibit the proliferation and migration of B cell tumor.
- Detailed Description
SHR1459 is a selective small molecule BTK inhibitor developed by Jiangsu Hengrui medicine Limited, by inhibiting the phosphorylation of BTK and down regulation of BCR signal transduction pathway, And then selectively inhibit the proliferation and migration of B cell tumor. The objective of this phase 1 study is to evaluate the safety and tolerance of SHR1459 in patients with replaced/refractory mature B cell neoplasms, in order to determine the maximum tolerated dose (MTD) and recommended dose for phase 2 clinical study (RP2D);
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 86
- ECOG Performance Status [PS] score must be 0 or 1;
- Life expectancy ≥ 12 weeks;
- Mature B cell eoplasmss with histological or cytological diagnosis, including diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL) , chronic lymphocytic leukemia/Small lymphocytic lymphoma (CLL/SLL), Mantle cell lymphoma (MCL), Marginal zone lymphoma (MZL) and waldenstrom macroglobulinemia (WM);
- The function of bone marrow is basically normal;
- Renal function is basically normal;
- Hepatic function is basically normal.
- Had received treatment with the compound of the same mechanism (BTK inhibitor);
- With infiltration of lymphoma central nervous system;
- Received autologous stem cell transplantation within 60 days before signing the informed consent, received allogeneic stem cell transplantation in 90 days (after allogeneic stem cell transplantation, if graft-versus-host disease appeared, it must be ≤ level 1, and if there was no prohibited medication, the screening could be performed);
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description SHR1459 SHR1459 Oral administration, once a day, 28 days for a cycle, until the disease progression or the intolerable toxicity occurs.
- Primary Outcome Measures
Name Time Method Incidence and severity of treatment-emergent adverse events (AEs) [Safety and Tolerability]) through study completion, an average of about 6 months The incidence and severity of treatment-emergent AEs will be collected and the safety and tolerability of SHR1459 will be assessed
Recommended phase 2 dose (RP2D) 28 days since the date of first dose Recommended phase 2 dose (RP2D) and/or maximum tolerated dose (MTD) will be established according to the incidence of dose-limiting toxicities (DLTs) of escalated doses of SHR1459
- Secondary Outcome Measures
Name Time Method Halflife (T1/2) Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle) Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Halflife (T1/2)
Apparent volume of distribution, steady state/bioavailability (Vss/F) Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle) Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Apparent volume of distribution, steady state/bioavailability (Vss/F)
Duration of Response (DoR) every 8 weeks through study completion, an average of about 6 months Assess the duration of complete/partial response after the treatment of SHR1459
Area under curve (AUC) Day 1 and Day 2 of the single dose Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Area under curve (AUC)
Maximum plasma concentration, steady state (Cmax,ss) Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle) Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Maximum plasma concentration, steady state (Cmax,ss)
Time to peak, steady state (Tmax,ss) Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle) Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Time to peak, steady state (Tmax,ss)
Time to Response (TTR) every 8 weeks through study completion, an average of about 6 months Assess time to response of SHR 1459 after treatment
Progression-free survival (PFS) every 8 weeks through study completion, an average of about 6 months Assess the survival condition of the subjects after the treatment of SHR1459
Time to peak (Tmax) Day 1 and Day 2 of the single dose Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Time to peak (Tmax) of plasma concentration
Maximum plasma concentration (Cmax) Day 1 and Day 2 of the single dose Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Maximum plasma concentration (Cmax)
Clearance/ bioavailability (CL/F) Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle) Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Clearance/ bioavailability (CL/F)
apparent volume of distribution/bioavailability (Vd/F) Day 1 and Day 2 of the single dose Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): apparent volume of distribution/bioavailability (Vd/F)
Area under curve, steady state (AUCss) Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle) Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Area under curve, steady state (AUCss)
Objective response rate (ORR) every 8 weeks through study completion, an average of about 6 months Assess the response rate of subjects to the treatment of SHR1459
Accumulation index (Rac) Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle) Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Accumulation index (Rac)
Trial Locations
- Locations (1)
Blood disease hospital of Chinese Academy of Medical Sciences
🇨🇳Tianjin, Tianjin, China