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

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
86

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Jiangsu HengRui Medicine Co., Ltd.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 6, 2018

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 30, 2023

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 30, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 6, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 7, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 10, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 14, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 10, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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