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

Primary Purpose

Mature B Cell Neoplasms

Status
Active
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
SHR1459
Sponsored by
Jiangsu HengRui Medicine Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mature B Cell Neoplasms focused on measuring replased/refractory mature B cell neoplasms, BTK inhibitor

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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);

Sites / Locations

  • Blood disease hospital of Chinese Academy of Medical Sciences

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

SHR1459

Arm Description

Oral administration, once a day, 28 days for a cycle, until the disease progression or the intolerable toxicity occurs.

Outcomes

Primary Outcome Measures

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
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

Secondary Outcome Measures

Objective response rate (ORR)
Assess the response rate of subjects to the treatment of SHR1459
Duration of Response (DoR)
Assess the duration of complete/partial response after the treatment of SHR1459
Progression-free survival (PFS)
Assess the survival condition of the subjects after the treatment of SHR1459
Time to Response (TTR)
Assess time to response of SHR 1459 after treatment
Time to peak (Tmax)
Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Time to peak (Tmax) of plasma concentration
Maximum plasma concentration (Cmax)
Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Maximum plasma concentration (Cmax)
Halflife (T1/2)
Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Halflife (T1/2)
Clearance/ bioavailability (CL/F)
Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Clearance/ bioavailability (CL/F)
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)
Area under curve (AUC)
Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Area under curve (AUC)
Area under curve, steady state (AUCss)
Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Area under curve, steady state (AUCss)
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)
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)
Halflife (T1/2)
Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Halflife (T1/2)
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)
Clearance/ bioavailability (CL/F)
Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Clearance/ bioavailability (CL/F)
Accumulation index (Rac)
Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Accumulation index (Rac)

Full Information

First Posted
September 6, 2018
Last Updated
November 10, 2022
Sponsor
Jiangsu HengRui Medicine Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT03664297
Brief Title
Tolerance and Pharmacokinetics of SHR1459 in Patients With Recurrent Replased/Refractory Mature B Cell Neoplasmstumor
Official Title
Phase 1 Study to Evaluate the Tolerance and Pharmacokinetics of SHR1459 in Patients With Recurrentreplased/Refractory Mature B Cell Neoplasms Tumor
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 6, 2018 (Actual)
Primary Completion Date
December 30, 2023 (Anticipated)
Study Completion Date
December 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jiangsu HengRui Medicine Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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);

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mature B Cell Neoplasms
Keywords
replased/refractory mature B cell neoplasms, BTK inhibitor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
86 (Actual)

8. Arms, Groups, and Interventions

Arm Title
SHR1459
Arm Type
Experimental
Arm Description
Oral administration, once a day, 28 days for a cycle, until the disease progression or the intolerable toxicity occurs.
Intervention Type
Drug
Intervention Name(s)
SHR1459
Other Intervention Name(s)
No other intervention
Intervention Description
SHR1459 will be administered continually till disease progression or unacceptable toxicity.
Primary Outcome Measure Information:
Title
Incidence and severity of treatment-emergent adverse events (AEs) [Safety and Tolerability])
Description
The incidence and severity of treatment-emergent AEs will be collected and the safety and tolerability of SHR1459 will be assessed
Time Frame
through study completion, an average of about 6 months
Title
Recommended phase 2 dose (RP2D)
Description
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
Time Frame
28 days since the date of first dose
Secondary Outcome Measure Information:
Title
Objective response rate (ORR)
Description
Assess the response rate of subjects to the treatment of SHR1459
Time Frame
every 8 weeks through study completion, an average of about 6 months
Title
Duration of Response (DoR)
Description
Assess the duration of complete/partial response after the treatment of SHR1459
Time Frame
every 8 weeks through study completion, an average of about 6 months
Title
Progression-free survival (PFS)
Description
Assess the survival condition of the subjects after the treatment of SHR1459
Time Frame
every 8 weeks through study completion, an average of about 6 months
Title
Time to Response (TTR)
Description
Assess time to response of SHR 1459 after treatment
Time Frame
every 8 weeks through study completion, an average of about 6 months
Title
Time to peak (Tmax)
Description
Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Time to peak (Tmax) of plasma concentration
Time Frame
Day 1 and Day 2 of the single dose
Title
Maximum plasma concentration (Cmax)
Description
Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Maximum plasma concentration (Cmax)
Time Frame
Day 1 and Day 2 of the single dose
Title
Halflife (T1/2)
Description
Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Halflife (T1/2)
Time Frame
Day 1 and Day 2 of the single dose
Title
Clearance/ bioavailability (CL/F)
Description
Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Clearance/ bioavailability (CL/F)
Time Frame
Day 1 and Day 2 of the single dose
Title
apparent volume of distribution/bioavailability (Vd/F)
Description
Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): apparent volume of distribution/bioavailability (Vd/F)
Time Frame
Day 1 and Day 2 of the single dose
Title
Area under curve (AUC)
Description
Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Area under curve (AUC)
Time Frame
Day 1 and Day 2 of the single dose
Title
Area under curve, steady state (AUCss)
Description
Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Area under curve, steady state (AUCss)
Time Frame
Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle)
Title
Maximum plasma concentration, steady state (Cmax,ss)
Description
Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Maximum plasma concentration, steady state (Cmax,ss)
Time Frame
Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle)
Title
Time to peak, steady state (Tmax,ss)
Description
Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Time to peak, steady state (Tmax,ss)
Time Frame
Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle)
Title
Halflife (T1/2)
Description
Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Halflife (T1/2)
Time Frame
Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle)
Title
Apparent volume of distribution, steady state/bioavailability (Vss/F)
Description
Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Apparent volume of distribution, steady state/bioavailability (Vss/F)
Time Frame
Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle)
Title
Clearance/ bioavailability (CL/F)
Description
Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Clearance/ bioavailability (CL/F)
Time Frame
Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle)
Title
Accumulation index (Rac)
Description
Pharmacokinetics profile of a single dose SHR1459 and its metabolite (plasma): Accumulation index (Rac)
Time Frame
Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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);
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lugui Qiu
Organizational Affiliation
Blood Institute of the Chinese Academy of Medical Sciences
Official's Role
Principal Investigator
Facility Information:
Facility Name
Blood disease hospital of Chinese Academy of Medical Sciences
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300000
Country
China

12. IPD Sharing Statement

Plan to Share IPD
No

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

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