Mature B Cell Neoplasms
Conditions
Keywords
replased/refractory mature B cell neoplasms, BTK inhibitor
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);
Interventions
DRUGSHR1459
SHR1459 will be administered continually till disease progression or unacceptable toxicity.
Sponsors
Jiangsu HengRui Medicine Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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);
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 Response (TTR) | every 8 weeks through study completion, an average of about 6 months | Assess time to response of SHR 1459 after treatment |
| 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) |
| Halflife (T1/2) | Day 1 and Day 2 of the single dose | Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Halflife (T1/2) |
| Clearance/ bioavailability (CL/F) | Day 1 and Day 2 of the single dose | Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Clearance/ bioavailability (CL/F) |
| 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 |
| 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) |
| 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) |
| 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) |
| 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) |
| 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) |
| 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) |
| 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 |
Countries
China
Outcome results
None listed