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

November 10, 2022 updated by: Jiangsu HengRui Medicine Co., Ltd.

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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);

Study Type

Interventional

Enrollment (Actual)

86

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Tianjin
      • Tianjin, Tianjin, China, 300000
        • Blood disease hospital of Chinese Academy of Medical Sciences

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 71 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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);

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: SHR1459
Oral administration, once a day, 28 days for a cycle, until the disease progression or the intolerable toxicity occurs.
Drug: SHR1459
SHR1459 will be administered continually till disease progression or unacceptable toxicity.
Other Names:
  • No other intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence and severity of treatment-emergent adverse events (AEs) [Safety and Tolerability])
Time Frame: 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
through study completion, an average of about 6 months
Recommended phase 2 dose (RP2D)
Time Frame: 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
28 days since the date of first dose

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate (ORR)
Time Frame: every 8 weeks through study completion, an average of about 6 months
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)
Time Frame: every 8 weeks through study completion, an average of about 6 months
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)
Time Frame: every 8 weeks through study completion, an average of about 6 months
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)
Time Frame: every 8 weeks through study completion, an average of about 6 months
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)
Time Frame: 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
Day 1 and Day 2 of the single dose
Maximum plasma concentration (Cmax)
Time Frame: Day 1 and Day 2 of the single dose
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)
Time Frame: Day 1 and Day 2 of the single dose
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)
Time Frame: Day 1 and Day 2 of the single dose
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)
Time Frame: 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)
Day 1 and Day 2 of the single dose
Area under curve (AUC)
Time Frame: Day 1 and Day 2 of the single dose
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)
Time Frame: 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)
Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle)
Maximum plasma concentration, steady state (Cmax,ss)
Time Frame: 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)
Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle)
Time to peak, steady state (Tmax,ss)
Time Frame: 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)
Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle)
Halflife (T1/2)
Time Frame: 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)
Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle)
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)
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)
Time Frame: 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)
Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle)
Accumulation index (Rac)
Time Frame: 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)
Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Jiangsu HengRui Medicine Co., Ltd.

Investigators

  • Principal Investigator: Lugui Qiu, Blood Institute of the Chinese Academy of Medical Sciences

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 6, 2018

Primary Completion (Anticipated)

December 30, 2023

Study Completion (Anticipated)

December 30, 2024

Study Registration Dates

First Submitted

September 6, 2018

First Submitted That Met QC Criteria

September 7, 2018

First Posted (Actual)

September 10, 2018

Study Record Updates

Last Update Posted (Actual)

November 14, 2022

Last Update Submitted That Met QC Criteria

November 10, 2022

Last Verified

November 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SHR1459-I-101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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