Tolerance and Pharmacokinetics of SHR1459 in Patients With Recurrent Replased/Refractory Mature B Cell Neoplasmstumor

Study Overview
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Brief Summary
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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
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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);

Official Title
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Phase 1 Study to Evaluate the Tolerance and Pharmacokinetics of SHR1459 in Patients With Recurrentreplased/Refractory Mature B Cell Neoplasms Tumor

Conditions
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Mature B Cell Neoplasms

Intervention / Treatment
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* Drug: SHR1459


Participation Criteria
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Eligibility Criteria
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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);

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHR1459<br>Oral administration, once a day, 28 days for a cycle, until the disease progression or the intolerable toxicity occurs. | Drug: SHR1459<br>* SHR1459 will be administered continually till disease progression or unacceptable toxicity.<br>* Other names: No other intervention;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of treatment-emergent adverse events (AEs) [Safety and Tolerability]) | The incidence and severity of treatment-emergent AEs will be collected and the safety and tolerability of SHR1459 will be assessed | through study completion, an average of about 6 months | 
| Recommended phase 2 dose (RP2D) | 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 | 28 days since the date of first dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | Assess the response rate of subjects to the treatment of SHR1459 | every 8 weeks through study completion, an average of about 6 months | 
| Duration of Response (DoR) | Assess the duration of complete/partial response after the treatment of SHR1459 | every 8 weeks through study completion, an average of about 6 months | 
| Progression-free survival (PFS) | Assess the survival condition of the subjects after the treatment of SHR1459 | every 8 weeks through study completion, an average of about 6 months | 
| Time to Response (TTR) | Assess time to response of SHR 1459 after treatment | every 8 weeks through study completion, an average of about 6 months | 
| Time to peak (Tmax) | Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Time to peak (Tmax) of plasma concentration | Day 1 and Day 2 of the single dose | 
| Maximum plasma concentration (Cmax) | Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Maximum plasma concentration (Cmax) | Day 1 and Day 2 of the single dose | 
| Halflife (T1/2) | Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Halflife (T1/2) | Day 1 and Day 2 of the single dose | 
| Clearance/ bioavailability (CL/F) | Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Clearance/ bioavailability (CL/F) | Day 1 and Day 2 of the single dose | 
| apparent volume of distribution/bioavailability (Vd/F) | Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): apparent volume of distribution/bioavailability (Vd/F) | Day 1 and Day 2 of the single dose | 
| Area under curve (AUC) | Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Area under curve (AUC) | Day 1 and Day 2 of the single dose | 
| Area under curve, steady state (AUCss) | Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Area under curve, steady state (AUCss) | Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle) | 
| Maximum plasma concentration, steady state (Cmax,ss) | Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Maximum plasma concentration, steady state (Cmax,ss) | Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle) | 
| Time to peak, steady state (Tmax,ss) | Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Time to peak, steady state (Tmax,ss) | Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle) | 
| Halflife (T1/2) | Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Halflife (T1/2) | Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle) | 
| Apparent volume of distribution, steady state/bioavailability (Vss/F) | Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Apparent volume of distribution, steady state/bioavailability (Vss/F) | Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle) | 
| Clearance/ bioavailability (CL/F) | Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Clearance/ bioavailability (CL/F) | Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle) | 
| Accumulation index (Rac) | Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Accumulation index (Rac) | Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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replased/refractory mature B cell neoplasms, BTK inhibitor