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出境医 / 临床实验 / A Clinical Study to Evaluate Pharmacokinetics, Safety, and Tolerability of Abexinostat in Chinese Patients

A Clinical Study to Evaluate Pharmacokinetics, Safety, and Tolerability of Abexinostat in Chinese Patients

Study Description
Brief Summary:
This is an open-label, non-randomized clinical study to evaluate the pharmacokinetic (PK) profiles, safety, tolerability and preliminary efficacy of oral abexinostat monotherapy in patients with non-Hodgkin's lymphoma who have failed standard of care, and thereby to determine the pharmacokinetic (PK) parameters, the maximum tolerated dose (MTD), and the recommended phase 2 dose (RP2D) of the oral monotherapy of abexinostat.

Condition or disease Intervention/treatment Phase
Non Hodgkin Lymphoma Drug: Abexinostat Phase 1 Phase 2

Detailed Description:

This is an open-label, non-randomized clinical study to evaluate the pharmacokinetic (PK) profiles, safety, tolerability and preliminary efficacy of oral abexinostat monotherapy in patients with non-Hodgkin's lymphoma who have failed standard of care, and thereby to determine the pharmacokinetic (PK) parameters, the maximum tolerated dose (MTD), and the recommended phase 2 dose (RP2D) of the oral monotherapy of abexinostat.

Three (3) dose groups are pre-set to include 40 mg BID, 60 mg BID and 80 mg BID,respectively.The pre-set dose group is subject to change during the study and the actual dosage increment is determined by the Data safety Monitoring Committee (DSMC). A total of 12-16 subjects in the RP2D dose group will be required to accept PK blood sampling for the analysis of PK profiles and parameters. The patients will continue treatment until the occurrence of a DLT event, disease progression, intolerant toxicity, withdrawal of ICF, treatment discontinuation determined by the investigator, lost to follow-up, death, or termination of the study, (whichever occurs first).

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description: Cohort 1: 40 mg BID Cohort 2: 60 mg BID Cohort 3: 80 mg BID
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Non-Randomized Clinical Study to Evaluate Pharmacokinetic (PK) Profiles, Safety, and Tolerability of Abexinostat Monotherapy in Patients With Non-Hodgkin's Lymphoma Who Have Failed Standard of Care
Actual Study Start Date : January 8, 2020
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2021
Arms and Interventions
Arm Intervention/treatment
Experimental: Dosing Cohorts
Three (3) dose cohorts are pre-set to include 40 mg BID, 60 mg BID and 80 mg BID,respectively.The pre-set dose group is subject to change during the study and the actual dosage increment is determined by the Data safety Monitoring Committee (DSMC).
Drug: Abexinostat
Abexinostat Tosylate Tablets

Outcome Measures
Primary Outcome Measures :
  1. Measure AUC at Different Dose Level [ Time Frame: Up to 6 month ]
    Measure Area under the plasma concentration versus time curve (AUC) levels at different dose level

  2. Measure Cmax at Different Dose Level [ Time Frame: Up to 6 month ]
    Measure Peak Plasma Concentration (Cmax at different dose level

  3. Determine the maximum tolerated dose [ Time Frame: Up to 6 month ]
    Determine the maximum tolerated dose based on observed dose-limiting toxicity at different dose levels


Secondary Outcome Measures :
  1. Measure Objective Response Rate [ Time Frame: Up to 12 Month ]
    Measure objective response rate in % at the RP2D in patients with non-Hodgkin's lymphoma who have failed standard of care

  2. Measure Duration of Response [ Time Frame: Up to 12 Month ]
    Measure duration of response in months at the RP2D in patients with non-Hodgkin's lymphoma who have failed standard of care


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed diagnosis o f non Hodgkin's lymphoma
  • Patients with non-Hodgkin's lymphoma who have either failed standard of care or are intolerant/unapplicable to therapy;
  • Subject who has no growth factor supportive therapy, transfusion of blood or blood products within 14 days before the enrollment test
  • The patient is capable and willing to accept the follow up according to the protocol and signed or provided the ICF signed by the legal representative
  • Contraceptive measures , definition of women of childbearing age and contraceptive requirements

Exclusion Criteria:

  • Subjects who have received anti tumor therapy and have not recovered from previous toxicity reactions ( toxicity reactions unrecovered to grade 1 as per NCI CTCAE 5.0
  • Subjects who received major surgery (excluding diagnostic biopsy)within 28 days prior to the first dose.
  • Subjects who received autologous stem cell transplantation within 3 months or allogeneic stem cell transplantation within 6 months prior to the first dose with active graft versus host response at screening
  • Subjects with use of prohibited medication within 7 days or less than 5 half lives prior to the first dose (whichever is shorter), see prohibited medication list
  • Participated in other interventional clinical trial within 1 month or 5 half life periods prior to the first dose (whichever is longer), except for non intervention clinical trials
  • Evidence suggests that there may be human immunodeficiency virus (HIV) infection , or hepatitis C (HCV) hepatitis virus infection PCR RNA positive);
  • Uncontrolled systemic infection or infection requiring intravenous injection of antibiotics
  • Lymphoma with central nervous system (CNS) involvement
  • Subjects with concurrent other malignant tumors in addition to the studied tumor within 2 years prior to the first dosing , except for the controlled skin basal cell carcinoma , cervical carcinoma in situ, ductal carcinoma in situ , and papillary thyroid carcinoma
  • Subject is known to be allergic to the components of abexinostat
  • Pregnant and lactating subjects
  • Upon the investigator's judgment , the subject has any disease or medical condition that is unstable or may affect safety or study compliance , such as uncontrolled hypertension,uncontrolled diabetes, active bleeding , etc.
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Bing Zhao, MD (01186)13716386801 bzhao@xynomicpharma.com
Contact: Sophia Paspal, Ph.D sophia.paspal@xynomicpharma.com

Locations
Layout table for location information
China
Cancer Hospital Chinese Academy of Medical Sciences Recruiting
Beijing, China, 100021
Contact: Shi Yuankai, MD, PhD    13701251865    syuankaipumc@126.com   
Principal Investigator: Shao Zonghong, MD         
Zhejiang Cancer Hospital Recruiting
Hangzhou, China, 310022
Contact: Yang Haiyan, MD, PhD    13857182590    haiyanyang1125@163.com   
Tianjin Medical University General Hospital Recruiting
Tianjin, China, 300052
Contact: Shao Zonghong, MD    13802036467    shaozonghong@sina.com   
The Affiliated Hospital of Xuzhou Medical University Recruiting
Xuzhou, China, 221006
Contact: Li Zhenyu, MD    13852439312    frankfeng_2004@126.com   
Sponsors and Collaborators
Xynomic Pharmaceuticals, Inc.
Chinese Academy of Medical Sciences
Investigators
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Principal Investigator: Yuankai Shi, M.D.; Prof Cancer Hospital Chinese Academy Of Medical Science
Tracking Information
First Submitted Date  ICMJE July 9, 2019
First Posted Date  ICMJE July 18, 2019
Last Update Posted Date May 12, 2021
Actual Study Start Date  ICMJE January 8, 2020
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 16, 2019)
  • Measure AUC at Different Dose Level [ Time Frame: Up to 6 month ]
    Measure Area under the plasma concentration versus time curve (AUC) levels at different dose level
  • Measure Cmax at Different Dose Level [ Time Frame: Up to 6 month ]
    Measure Peak Plasma Concentration (Cmax at different dose level
  • Determine the maximum tolerated dose [ Time Frame: Up to 6 month ]
    Determine the maximum tolerated dose based on observed dose-limiting toxicity at different dose levels
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 16, 2019)
  • Measure Objective Response Rate [ Time Frame: Up to 12 Month ]
    Measure objective response rate in % at the RP2D in patients with non-Hodgkin's lymphoma who have failed standard of care
  • Measure Duration of Response [ Time Frame: Up to 12 Month ]
    Measure duration of response in months at the RP2D in patients with non-Hodgkin's lymphoma who have failed standard of care
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Clinical Study to Evaluate Pharmacokinetics, Safety, and Tolerability of Abexinostat in Chinese Patients
Official Title  ICMJE An Open-Label, Non-Randomized Clinical Study to Evaluate Pharmacokinetic (PK) Profiles, Safety, and Tolerability of Abexinostat Monotherapy in Patients With Non-Hodgkin's Lymphoma Who Have Failed Standard of Care
Brief Summary This is an open-label, non-randomized clinical study to evaluate the pharmacokinetic (PK) profiles, safety, tolerability and preliminary efficacy of oral abexinostat monotherapy in patients with non-Hodgkin's lymphoma who have failed standard of care, and thereby to determine the pharmacokinetic (PK) parameters, the maximum tolerated dose (MTD), and the recommended phase 2 dose (RP2D) of the oral monotherapy of abexinostat.
Detailed Description

This is an open-label, non-randomized clinical study to evaluate the pharmacokinetic (PK) profiles, safety, tolerability and preliminary efficacy of oral abexinostat monotherapy in patients with non-Hodgkin's lymphoma who have failed standard of care, and thereby to determine the pharmacokinetic (PK) parameters, the maximum tolerated dose (MTD), and the recommended phase 2 dose (RP2D) of the oral monotherapy of abexinostat.

Three (3) dose groups are pre-set to include 40 mg BID, 60 mg BID and 80 mg BID,respectively.The pre-set dose group is subject to change during the study and the actual dosage increment is determined by the Data safety Monitoring Committee (DSMC). A total of 12-16 subjects in the RP2D dose group will be required to accept PK blood sampling for the analysis of PK profiles and parameters. The patients will continue treatment until the occurrence of a DLT event, disease progression, intolerant toxicity, withdrawal of ICF, treatment discontinuation determined by the investigator, lost to follow-up, death, or termination of the study, (whichever occurs first).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description:
Cohort 1: 40 mg BID Cohort 2: 60 mg BID Cohort 3: 80 mg BID
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non Hodgkin Lymphoma
Intervention  ICMJE Drug: Abexinostat
Abexinostat Tosylate Tablets
Study Arms  ICMJE Experimental: Dosing Cohorts
Three (3) dose cohorts are pre-set to include 40 mg BID, 60 mg BID and 80 mg BID,respectively.The pre-set dose group is subject to change during the study and the actual dosage increment is determined by the Data safety Monitoring Committee (DSMC).
Intervention: Drug: Abexinostat
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 16, 2019)
25
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2021
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically confirmed diagnosis o f non Hodgkin's lymphoma
  • Patients with non-Hodgkin's lymphoma who have either failed standard of care or are intolerant/unapplicable to therapy;
  • Subject who has no growth factor supportive therapy, transfusion of blood or blood products within 14 days before the enrollment test
  • The patient is capable and willing to accept the follow up according to the protocol and signed or provided the ICF signed by the legal representative
  • Contraceptive measures , definition of women of childbearing age and contraceptive requirements

Exclusion Criteria:

  • Subjects who have received anti tumor therapy and have not recovered from previous toxicity reactions ( toxicity reactions unrecovered to grade 1 as per NCI CTCAE 5.0
  • Subjects who received major surgery (excluding diagnostic biopsy)within 28 days prior to the first dose.
  • Subjects who received autologous stem cell transplantation within 3 months or allogeneic stem cell transplantation within 6 months prior to the first dose with active graft versus host response at screening
  • Subjects with use of prohibited medication within 7 days or less than 5 half lives prior to the first dose (whichever is shorter), see prohibited medication list
  • Participated in other interventional clinical trial within 1 month or 5 half life periods prior to the first dose (whichever is longer), except for non intervention clinical trials
  • Evidence suggests that there may be human immunodeficiency virus (HIV) infection , or hepatitis C (HCV) hepatitis virus infection PCR RNA positive);
  • Uncontrolled systemic infection or infection requiring intravenous injection of antibiotics
  • Lymphoma with central nervous system (CNS) involvement
  • Subjects with concurrent other malignant tumors in addition to the studied tumor within 2 years prior to the first dosing , except for the controlled skin basal cell carcinoma , cervical carcinoma in situ, ductal carcinoma in situ , and papillary thyroid carcinoma
  • Subject is known to be allergic to the components of abexinostat
  • Pregnant and lactating subjects
  • Upon the investigator's judgment , the subject has any disease or medical condition that is unstable or may affect safety or study compliance , such as uncontrolled hypertension,uncontrolled diabetes, active bleeding , etc.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Bing Zhao, MD (01186)13716386801 bzhao@xynomicpharma.com
Contact: Sophia Paspal, Ph.D sophia.paspal@xynomicpharma.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04024696
Other Study ID Numbers  ICMJE XYN-609
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Xynomic Pharmaceuticals, Inc.
Study Sponsor  ICMJE Xynomic Pharmaceuticals, Inc.
Collaborators  ICMJE Chinese Academy of Medical Sciences
Investigators  ICMJE
Principal Investigator: Yuankai Shi, M.D.; Prof Cancer Hospital Chinese Academy Of Medical Science
PRS Account Xynomic Pharmaceuticals, Inc.
Verification Date May 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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