search
Back to results

Tolerability and Pharmacokinetics Study of TQB3702 Tablets in Hematologic Tumor Subjects

Primary Purpose

Hematologic Malignancy

Status
Not yet recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
TQB3702 tablets
Sponsored by
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hematologic Malignancy

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Subjects voluntarily joined the study, signed informed consent form, and with good compliance. ≥18 years old and ≤ 80 years old; Eastern Cooperative Oncology Group (ECOG) physical status: 0-2; at least 3 months expected survival period. Clearly diagnosed recurrent / refractory hematological tumors that meet the WHO definition; At least 1 measurable lesion for efficacy evaluation. The function of main organs is normal. Female patients of childbearing age should agree to use contraceptive measures during the study period and for at least 6 months after study is stopped; a negative serum pregnancy test within 7 days prior to study enrollment and must be non-lactating subjects; male patients should agree to use contraception during the study period and for at least 6 months after study is stopped. Exclusion Criteria: Patients has had or is currently having other malignant tumors within 3 years. The following two conditions can be included in the group: other malignant tumors treated with a single operation to achieved 5 consecutive years of disease free survival (DFS)s. Cured cervical carcinoma in situ, non-melanoma skin cancer, nasopharyngeal carcinoma and superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor infiltrating basement membrane)]. Subjects with central nervous system aggression (CNS); Received allogeneic hematopoietic stem cell transplantation (allo-HSCT) or had active graft-versus-host disease (GVHD) requiring immunosuppressive therapy within 12 months before the first dose; Multiple factors that affect the absorption of oral medications (e.g., inability to swallow, chronic diarrhea, and intestinal obstruction); Unrelieved toxicity of ≥CTC AE grade 1 due to any previous treatment, excluding alopecia and fatigue; Major surgical treatment, open biopsy, and significant traumatic injury were received within 28 days before the start of study treatment. The presence of active or uncontrolled primary autoimmune cytopenia, including autoimmune hemolytic anemia (AIHA) and primary immune thrombocytopenia (ITP); Patients with evidence or history of bleeding constitution; Or any bleeding event (such as gastrointestinal bleeding) greater than or equal to CTC AE level 3 within 4 weeks before the first medication; Subjects had an arteriovenous thrombosis event within 6 months. Subjects have history of psychotropic substance abuse and are unable to abstain or have mental disorders; Subjects with any severe and/or uncontrolled disease. Within 2 weeks before the first treatment, the subjects had received proprietary Chinese medicines with anti-tumor indications specified in the NMPA approved drug instructions; Uncontrolled pleural effusion, pericardial effusion, or ascites that still require repeated drainage (investigator judgment); Study treatment related: subjects received live or mRNA vaccines within 4 weeks before the first treatment or were scheduled to receive live or mRNA vaccines during the study; Participated in clinical trials of other antitumor drugs within 4 weeks before the first treatment; According to the investigator's judgment, there are concomitant diseases that seriously endanger the safety of the subjects or affect the completion of the study, or subjects who are considered unsuitable for enrollment for other reasons.

Sites / Locations

  • The First Affiliated Hospital of Nanchang University
  • The Cancer Hospital Affiliated to Shandong First Medical University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

TQB3702 tablets

Arm Description

TQB3702 tablets were administered orally, 28 days as a treatment cycle until the progressive diseases or the investigator judges that it is not suitable for subject to continue to take this medicine.

Outcomes

Primary Outcome Measures

Maximum tolerated dose (MTD)
To evaluate the maximum tolerated dose of TQB3702 tablets in the treatment of relapsed/refractory hematologic tumors.
Dose limited toxicity (DLT)
To evaluate the dose-limiting toxic dose of TQB3702 tablets in the treatment of relapsed/refractory hematologic tumors.
Recommended Phase II Dose (RP2D)
To evaluate the phase II recommended dose of TQB3702 tablets in the treatment of relapsed/refractory hematological tumors.

Secondary Outcome Measures

Time to Reach the Maximum Plasma Concentration (Tmax)-single dose
Time to Reach the Maximum Plasma Concentration after single dose
Time to Reach the Maximum Plasma Concentration (Tmax)-multiple dose
Time to Reach the Maximum Plasma Concentration after multiple dose
Maximum plasma concentration (Cmax)-Single dose
Cmax is the maximum plasma concentration of TQB3702 after single dose
Maximum plasma concentration (Cmax)-Multiple dose
Cmax is the maximum plasma concentration of TQB3702 after multiple dose
Elimination half-life (t1/2)-Single dose
t1/2 is time it takes for the blood concentration of TQB3702 or metabolite(s) to drop by half after single dose.
Elimination half-life (t1/2)-Multiple dose
t1/2 is time it takes for the blood concentration of TQB3702 or metabolite(s) to drop by half after multiple dose.
Area under the plasma concentration-time curve from time zero to time t (AUC0-t)-Single dose
To characterize the pharmacokinetics of TQB3702 by assessment of area under the plasma concentration time curve from the first dose to a certain time.
Area under the plasma concentration-time curve from time zero to time t (AUC0-t)-Multiple dose
To characterize the pharmacokinetics of TQB3702 by assessment of area under the plasma concentration time curve from the first dose to a certain time.
Maximum (peak) steady-state plasma drug concentration during a dosage interval (Cmax,ss)-Single dose
Maximum (peak) steady-state plasma drug concentration during a dosage interval (Cmax,ss) after Single dose
Maximum (peak) steady-state plasma drug concentration during a dosage interval (Cmax,ss)-Multiple dose
Maximum (peak) steady-state plasma drug concentration during a dosage interval (Cmax,ss) after Multiple dose
steady state area under the concentration-time curve over a dosing interval (AUCtau, ss)-single dose
steady state area under the concentration-time curve over a dosing interval (AUCtau, ss) after single dose
steady state area under the concentration-time curve over a dosing interval (AUCtau, ss)-multiple dose
steady state area under the concentration-time curve over a dosing interval (AUCtau, ss) after multiple dose
Minimum steady-state plasma drug concentration during a dosage interval (Css-min)-Single dose
Minimum steady-state plasma drug concentration during a dosage interval (Cmin-ss) after Single dose
Minimum steady-state plasma drug concentration during a dosage interval (Css-min)-multiple dose
Minimum steady-state plasma drug concentration during a dosage interval (Cmin-ss) after multiple dose
Objective Response Rate (ORR)
The proportion of patients with tumor size reduction of a predefined amount and for a minimum time period
Complete Remission Rate (CRR)
The proportion of tumors that have a complete response after treatment
Disease Control Rate (DCR)
The percentage of patients with advanced or metastatic cancer who have achieved complete response, partial response and stable disease to a cancer treatment in clinical trials.
Duration of Response (DOR)
The time from the date of first documentation of a CR or PR or PD to the date of first documentation of tumor progression.
Progression Free Survival (PFS)
The time from the first dose to the first documentation of progressive disease (PD) or death from any cause, whichever occurs first
Overall Survival (OS)
the time from start of study treatment to date of death due to any cause
Adverse events (AE)
The occurrence of all adverse events (AE)
Serious adverse events (SAE)
The occurrence of all serious adverse events (SAE)
Bruton's tyrosine kinase (BTK) occupancy
The BTK occupancy in peripheral blood mononuclear cell (PMBC)

Full Information

First Posted
November 2, 2022
Last Updated
November 2, 2022
Sponsor
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
search

1. Study Identification

Unique Protocol Identification Number
NCT05610202
Brief Title
Tolerability and Pharmacokinetics Study of TQB3702 Tablets in Hematologic Tumor Subjects
Official Title
Phase I Clinical Trial of Tolerability and Pharmacokinetics of TQB3702 Tablets in Hematologic Tumor Subjects
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
November 2022 (Anticipated)
Primary Completion Date
August 2024 (Anticipated)
Study Completion Date
August 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Chia Tai Tianqing Pharmaceutical Group 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
This project is an open, dose escalation and expansion phase I clinical study. The first phase is a dose escalation study, and the second phase is a dose expansion study based on the Maximum tolerated dose (MTD) / Recommended Phase II Dose (RP2D) obtained in the first phase. The purpose is to evaluate the tolerability and preliminary efficacy of TQB3702 tablets in hematological tumor subjects.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematologic Malignancy

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
TQB3702 tablets
Arm Type
Experimental
Arm Description
TQB3702 tablets were administered orally, 28 days as a treatment cycle until the progressive diseases or the investigator judges that it is not suitable for subject to continue to take this medicine.
Intervention Type
Drug
Intervention Name(s)
TQB3702 tablets
Intervention Description
TQB3702 tablets are selective BTK inhibitors.
Primary Outcome Measure Information:
Title
Maximum tolerated dose (MTD)
Description
To evaluate the maximum tolerated dose of TQB3702 tablets in the treatment of relapsed/refractory hematologic tumors.
Time Frame
Baseline up to 104 weeks
Title
Dose limited toxicity (DLT)
Description
To evaluate the dose-limiting toxic dose of TQB3702 tablets in the treatment of relapsed/refractory hematologic tumors.
Time Frame
Baseline up to 104 weeks
Title
Recommended Phase II Dose (RP2D)
Description
To evaluate the phase II recommended dose of TQB3702 tablets in the treatment of relapsed/refractory hematological tumors.
Time Frame
Baseline up to 104 weeks
Secondary Outcome Measure Information:
Title
Time to Reach the Maximum Plasma Concentration (Tmax)-single dose
Description
Time to Reach the Maximum Plasma Concentration after single dose
Time Frame
before administration, 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24, 48, 72hours after administration.
Title
Time to Reach the Maximum Plasma Concentration (Tmax)-multiple dose
Description
Time to Reach the Maximum Plasma Concentration after multiple dose
Time Frame
before administration (-1~0h), 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24 hours after administration at Day 8/15/28 of Cycle1, Day 28 of Cycle 6; when withdrawn from the group due to disease progression or at the end of study treatment.
Title
Maximum plasma concentration (Cmax)-Single dose
Description
Cmax is the maximum plasma concentration of TQB3702 after single dose
Time Frame
before administration, 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24, 48, 72hours after administration.
Title
Maximum plasma concentration (Cmax)-Multiple dose
Description
Cmax is the maximum plasma concentration of TQB3702 after multiple dose
Time Frame
before administration (-1~0h), 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24 hours after administration at Day 8/15/28 of Cycle1, Day 28 of Cycle 6; when withdrawn from the group due to disease progression or at the end of study treatment.
Title
Elimination half-life (t1/2)-Single dose
Description
t1/2 is time it takes for the blood concentration of TQB3702 or metabolite(s) to drop by half after single dose.
Time Frame
before administration, 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24, 48, 72 hours after administration.
Title
Elimination half-life (t1/2)-Multiple dose
Description
t1/2 is time it takes for the blood concentration of TQB3702 or metabolite(s) to drop by half after multiple dose.
Time Frame
before administration (-1~0h), 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24 hours after administration at Day 8/15/28 of Cycle1, Day 28 of Cycle 6; when withdrawn from the group due to disease progression or at the end of study treatment.
Title
Area under the plasma concentration-time curve from time zero to time t (AUC0-t)-Single dose
Description
To characterize the pharmacokinetics of TQB3702 by assessment of area under the plasma concentration time curve from the first dose to a certain time.
Time Frame
before administration, 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24, 48, 72hours after administration.
Title
Area under the plasma concentration-time curve from time zero to time t (AUC0-t)-Multiple dose
Description
To characterize the pharmacokinetics of TQB3702 by assessment of area under the plasma concentration time curve from the first dose to a certain time.
Time Frame
before administration (-1~0h), 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24 hours after administration at Day 8/15/28 of Cycle1, Day 28 of Cycle 6; when withdrawn from the group due to disease progression or at the end of study treatment.
Title
Maximum (peak) steady-state plasma drug concentration during a dosage interval (Cmax,ss)-Single dose
Description
Maximum (peak) steady-state plasma drug concentration during a dosage interval (Cmax,ss) after Single dose
Time Frame
before administration, 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24, 48, 72hours after administration.
Title
Maximum (peak) steady-state plasma drug concentration during a dosage interval (Cmax,ss)-Multiple dose
Description
Maximum (peak) steady-state plasma drug concentration during a dosage interval (Cmax,ss) after Multiple dose
Time Frame
before administration (-1~0h), 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24 hours after administration at Day 8/15/28 of Cycle1, Day 28 of Cycle 6; when withdrawn from the group due to disease progression or at the end of study treatment.
Title
steady state area under the concentration-time curve over a dosing interval (AUCtau, ss)-single dose
Description
steady state area under the concentration-time curve over a dosing interval (AUCtau, ss) after single dose
Time Frame
before administration, 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24, 48, 72hours after administration.
Title
steady state area under the concentration-time curve over a dosing interval (AUCtau, ss)-multiple dose
Description
steady state area under the concentration-time curve over a dosing interval (AUCtau, ss) after multiple dose
Time Frame
before administration (-1~0h), 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24 hours after administration at Day 8/15/28 of Cycle1, Day 28 of Cycle 6; when withdrawn from the group due to disease progression or at the end of study treatment.
Title
Minimum steady-state plasma drug concentration during a dosage interval (Css-min)-Single dose
Description
Minimum steady-state plasma drug concentration during a dosage interval (Cmin-ss) after Single dose
Time Frame
before administration, 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24, 48, 72hours after administration.
Title
Minimum steady-state plasma drug concentration during a dosage interval (Css-min)-multiple dose
Description
Minimum steady-state plasma drug concentration during a dosage interval (Cmin-ss) after multiple dose
Time Frame
before administration (-1~0h), 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24 hours after administration at Day 8/15/28 of Cycle1, Day 28 of Cycle 6; when withdrawn from the group due to disease progression or at the end of study treatment.
Title
Objective Response Rate (ORR)
Description
The proportion of patients with tumor size reduction of a predefined amount and for a minimum time period
Time Frame
Baseline up to 104 weeks
Title
Complete Remission Rate (CRR)
Description
The proportion of tumors that have a complete response after treatment
Time Frame
Baseline up to 104 weeks
Title
Disease Control Rate (DCR)
Description
The percentage of patients with advanced or metastatic cancer who have achieved complete response, partial response and stable disease to a cancer treatment in clinical trials.
Time Frame
Baseline up to 104 weeks
Title
Duration of Response (DOR)
Description
The time from the date of first documentation of a CR or PR or PD to the date of first documentation of tumor progression.
Time Frame
Baseline up to 104 weeks
Title
Progression Free Survival (PFS)
Description
The time from the first dose to the first documentation of progressive disease (PD) or death from any cause, whichever occurs first
Time Frame
Baseline up to 104 weeks
Title
Overall Survival (OS)
Description
the time from start of study treatment to date of death due to any cause
Time Frame
Baseline up to 104 weeks
Title
Adverse events (AE)
Description
The occurrence of all adverse events (AE)
Time Frame
Baseline up to 104 weeks
Title
Serious adverse events (SAE)
Description
The occurrence of all serious adverse events (SAE)
Time Frame
Baseline up to 104 weeks
Title
Bruton's tyrosine kinase (BTK) occupancy
Description
The BTK occupancy in peripheral blood mononuclear cell (PMBC)
Time Frame
Baseline up to 104 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects voluntarily joined the study, signed informed consent form, and with good compliance. ≥18 years old and ≤ 80 years old; Eastern Cooperative Oncology Group (ECOG) physical status: 0-2; at least 3 months expected survival period. Clearly diagnosed recurrent / refractory hematological tumors that meet the WHO definition; At least 1 measurable lesion for efficacy evaluation. The function of main organs is normal. Female patients of childbearing age should agree to use contraceptive measures during the study period and for at least 6 months after study is stopped; a negative serum pregnancy test within 7 days prior to study enrollment and must be non-lactating subjects; male patients should agree to use contraception during the study period and for at least 6 months after study is stopped. Exclusion Criteria: Patients has had or is currently having other malignant tumors within 3 years. The following two conditions can be included in the group: other malignant tumors treated with a single operation to achieved 5 consecutive years of disease free survival (DFS)s. Cured cervical carcinoma in situ, non-melanoma skin cancer, nasopharyngeal carcinoma and superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor infiltrating basement membrane)]. Subjects with central nervous system aggression (CNS); Received allogeneic hematopoietic stem cell transplantation (allo-HSCT) or had active graft-versus-host disease (GVHD) requiring immunosuppressive therapy within 12 months before the first dose; Multiple factors that affect the absorption of oral medications (e.g., inability to swallow, chronic diarrhea, and intestinal obstruction); Unrelieved toxicity of ≥CTC AE grade 1 due to any previous treatment, excluding alopecia and fatigue; Major surgical treatment, open biopsy, and significant traumatic injury were received within 28 days before the start of study treatment. The presence of active or uncontrolled primary autoimmune cytopenia, including autoimmune hemolytic anemia (AIHA) and primary immune thrombocytopenia (ITP); Patients with evidence or history of bleeding constitution; Or any bleeding event (such as gastrointestinal bleeding) greater than or equal to CTC AE level 3 within 4 weeks before the first medication; Subjects had an arteriovenous thrombosis event within 6 months. Subjects have history of psychotropic substance abuse and are unable to abstain or have mental disorders; Subjects with any severe and/or uncontrolled disease. Within 2 weeks before the first treatment, the subjects had received proprietary Chinese medicines with anti-tumor indications specified in the NMPA approved drug instructions; Uncontrolled pleural effusion, pericardial effusion, or ascites that still require repeated drainage (investigator judgment); Study treatment related: subjects received live or mRNA vaccines within 4 weeks before the first treatment or were scheduled to receive live or mRNA vaccines during the study; Participated in clinical trials of other antitumor drugs within 4 weeks before the first treatment; According to the investigator's judgment, there are concomitant diseases that seriously endanger the safety of the subjects or affect the completion of the study, or subjects who are considered unsuitable for enrollment for other reasons.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zengjun Li, Doctor
Phone
+86-13642138692
Email
zengjunli@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Fei Li, Doctor
Phone
+86-13970038386
Email
yx021021@sina.com
Facility Information:
Facility Name
The First Affiliated Hospital of Nanchang University
City
Nanchang
State/Province
Jiangxi
ZIP/Postal Code
330006
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fei Li, Doctor
Phone
+86-13970038386
Email
yx021021@sina.com
Facility Name
The Cancer Hospital Affiliated to Shandong First Medical University
City
Jinan
State/Province
Shandong
ZIP/Postal Code
250117
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zengjun Li, Doctor
Phone
+86-13642138692
Email
zengjunli@163.com

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Tolerability and Pharmacokinetics Study of TQB3702 Tablets in Hematologic Tumor Subjects

We'll reach out to this number within 24 hrs