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

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ClinicalTrials.gov Identifier: NCT03664297
Recruitment Status : Recruiting
First Posted : September 10, 2018
Last Update Posted : September 10, 2018
Sponsor:
Information provided by (Responsible Party):
Jiangsu HengRui Medicine Co., Ltd.

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.

Condition or disease Intervention/treatment Phase
Mature B Cell Neoplasms Drug: SHR1459 Phase 1

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);

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1 Study to Evaluate the Tolerance and Pharmacokinetics of SHR1459 in Patients With Recurrentreplased/Refractory Mature B Cell Neoplasms Tumor
Actual Study Start Date : February 6, 2018
Estimated Primary Completion Date : December 31, 2018
Estimated Study Completion Date : December 31, 2020

Resource links provided by the National Library of Medicine


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 Name: No other intervention




Primary Outcome Measures :
  1. 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

  2. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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)

  7. 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)

  8. 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)

  9. 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)

  10. 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)

  11. 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)

  12. 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)

  13. 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)

  14. 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)

  15. 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)

  16. 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)

  17. 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)



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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);

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03664297


Contacts
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Contact: Lugui Qiu, MD +86 13821266638 drqiu99@mdemail.com.cn
Contact: Junyuan Qi, MD +86 18622662361

Locations
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China, Tianjin
Blood disease hospital of Chinese Academy of Medical Sciences Recruiting
Tianjin, Tianjin, China, 300000
Contact: Lugui Qiu, MD    +86 13821266638    drqiu99@medmail.com.cn   
Sponsors and Collaborators
Jiangsu HengRui Medicine Co., Ltd.
Investigators
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Principal Investigator: Lugui Qiu Blood Institute of the Chinese Academy of Medical Sciences

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Responsible Party: Jiangsu HengRui Medicine Co., Ltd.
ClinicalTrials.gov Identifier: NCT03664297     History of Changes
Other Study ID Numbers: SHR1459-I-101
First Posted: September 10, 2018    Key Record Dates
Last Update Posted: September 10, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Jiangsu HengRui Medicine Co., Ltd.:
replased/refractory mature B cell neoplasms
BTK inhibitor

Additional relevant MeSH terms:
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Lymphoma, B-Cell
Neoplasms
Lymphoma, Non-Hodgkin
Lymphoma
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases