A Study of TQB3454 Tablets in Patients With Blood Tumors

January 12, 2024 updated by: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

A Phase Ib Clinical Trial of TQB3454 Tablets in Patients With Blood Tumors

The purpose of this clinical trial is to evaluate the safety of TQB3454 tablets in patients with acute myeloid leukemia and myelodysplastic syndrome, and determine the phase II recommended dose.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

80

Phase

  • Phase 2
  • 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 Contact

Study Locations

  • China
    • Anhui
      • Bengbu, Anhui, China, 233000
        • Recruiting
        • The First Affiliated Hospital of Bengbu Medical College
        • Contact:
    • Hebei
      • Cangzhou, Hebei, China, 061000
        • Recruiting
        • Cangzhou People's Hospital
        • Contact:
      • Chengde, Hebei, China, 067000
        • Recruiting
        • The Affiliated Hospital of Chengde Medical College
        • Contact:
    • Henan
      • Zhengzhou, Henan, China, 450000
        • Recruiting
        • Henan Cancer Hospital
        • Contact:
    • Hubei
      • Wuhan, Hubei, China, 430022
        • Recruiting
        • Union Hospital Tongji Medical College of Huazhong University of Science and Technology
        • Contact:
    • Jiangsu
      • Suzhou, Jiangsu, China, 215000
        • Recruiting
        • The First Affiliated Hospital of Soochow University
        • Contact:
      • Wuxi, Jiangsu, China, 214023
        • Recruiting
        • Wuxi People's Hospital
        • Contact:
    • Shandong
      • Binzhou, Shandong, China, 264008
        • Recruiting
        • Affiliated Hospital of Binzhou Medical College
        • Contact:
      • Yantai, Shandong, China, 264008
        • Recruiting
        • Yantai Mountain Hospital
        • Contact:
      • Yantai, Shandong, China, 264008
        • Recruiting
        • Yantai Yuhuangding Hospital
        • Contact:
    • Shanghai
      • Shanghai, Shanghai, China, 200233
      • Shanghai, Shanghai, China, 200437
        • Recruiting
        • Yueyang Hospital of Integrated Traditional Chinese and Western Medicine affiliated to Shanghai University of Traditional Chinese Medicine
        • Contact:
      • Shanghai, Shanghai, China, 200092
        • Recruiting
        • Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine
        • Contact:
      • Shanghai, Shanghai, China, 200040
        • Recruiting
        • HuaShan Hospital Affiliated To Fudan University
        • Contact:
      • Shanghai, Shanghai, China, 200000
        • Recruiting
        • Shanghai Tongren Hospital
        • Contact:
    • Sichuan
      • Chengdu, Sichuan, China, 610041
        • Recruiting
        • West China Hospital, Sichuan University
        • Contact:
    • Tianjin
      • Tianjin, Tianjin, China, 300020
        • Recruiting
        • Hospital of Hematology, Chinese Academy of Medical Sciences
        • Contact:

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients voluntarily joined the study and signed informed consent with good compliance.
  • Men and women; The expected survival is ≥3 months.
  • Negative serum/urine pregnancy test within 7 days prior to initial dose and must be non-lactating; Women of childbearing age agree to use contraception (such as an intrauterine device, birth control pill or condom) during the study and for six months after the study completion; Men agreed to use contraception during the study period and for six months after the end of the study.
  • The major organs are functioning well;

  • For Relapsing/refractory acute myeloid leukemia (AML):

    1. According to the classification criteria for Hematopoietic and lymphoid tissue tumors revised by the World Health Organization (WHO) in 2016, AML confirmed by bone marrow cell morphology, excluding acute promyelocytic leukemia (APL).
    2. ≥18 years old; Eastern Cooperative Oncology Group (ECOG) score is 0~2.
    3. Blood biochemical examination:

    i: Total bilirubin (TBIL) ≤1.5× upper limit of normal value (ULN), liver infiltration ≤3×ULN in Gilbert syndrome patients or tumor diseases; ii: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN; ALT and AST≤5×ULN if liver infiltration was associated.

  • For myelodysplastic syndrome (MDS) with higher risk:

    1. MDS patients were confirmed by bone marrow cell morphology and cytogenetics and met the classification criteria of hematopoietic and lymphoid tissue tumors revised by WHO in 2016.
    2. ≥18 years old; ECOG score is 0~2. c. Blood biochemical examination:

    i: Total bilirubin (TBIL) ≤1.5× upper limit of normal value (ULN), liver infiltration ≤3×ULN in Gilbert syndrome patients or tumor diseases.

ii: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN; ALT and AST≤5×ULN if concomitant with liver infiltration.

Exclusion Criteria:

  • Tumor diseases and history:

    1. The tumor has or is suspected to involve the central nervous system, or primary Central nervous system leukemia.
    2. Present or present with other malignant tumors within 3 years prior to the first dose. Except the following conditions: for other malignancies treated with a single operation, achieving a 5-year continuous disease-free survival (DFS); Cured cervical carcinoma in situ, non-melanoma skin cancer, and superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ), and T1 (tumor infiltrating basal membrane)].
    3. Severe life-threatening complications of leukemia, such as uncontrolled bleeding, hypoxia or shock pneumonia, and disseminated intravascular coagulation.

  • Previous antitumor therapy:

    1. Received National Medical Products Administration (NMPA) approved Chinese patent drugs with anticancer indications specified in the drug label within 2 weeks prior to initial administration.

    2. Toxicities associated with previous antineoplastic therapy did not return to CTCAE≤1, except for hair loss, fatigue and poor appetite.

      3. Associated diseases and history:

    1. Abnormal liver.
    2. Renal abnormalities.
    3. Gastrointestinal abnormalities.
    4. Cardio-cerebrovascular abnormalities.
    5. Immune-related history.
    6. Lung disease.
    7. Comorbidities that were severe or poorly controlled and, in the investigator's judgment, significantly compromised patient safety or hindered study completion.
    8. Risk of bleeding.
  • History of drug abuse or drug abuse.
  • Participated in clinical trials of other drugs within the past 30 days;
  • It is estimated that the patient's compliance to participate in this clinical study is insufficient.

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: TQB3454 Tablets
TQB3454 Tablets, orally administered, 28 days as a treatment cycle.
Drug: TQB3454 Tablets
TQB3454 Tablets is a selective isocitrate dehydrogenase 1 (IDH1) mutation inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The rate of all adverse events (AEs), serious adverse events (SAEs)
Time Frame: Up to 80 weeks
Proportion of patients with adverse events/serious adverse events, as defined by Common Terminology Criteria for Adverse Events (CTCAE5.0)
Up to 80 weeks
The severity of all adverse events (AEs), serious adverse events (SAEs)
Time Frame: Up to 80 weeks
The severity of adverse events/serious adverse events, as defined by Common Terminology Criteria for Adverse Events (CTCAE5.0)
Up to 80 weeks
Incidence of abnormal laboratory values
Time Frame: Up to 80 weeks
The proportion of patients with abnormal laboratory examination indicators mainly included blood routine, blood routine, blood biochemistry, coagulation function, thyroid function, myocardial enzyme profile, urine routine, stool routine and 12-lead electrocardiogram.
Up to 80 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Peak time (Tmax)
Time Frame: Cohort 1: pre-dose on Day 1, 14, 28 of Cycle 1, Day 14, 28 of Cycle 2. 2, 3, 4, 10, 24 hours after dose on Cycle1 Day28. Cohort 2: pre-dose, 2, 3, 4, 10, 24 hours after dose on Day 1, 28 of Cycle 1. Pre-dose on Day 14, 28 of Cycle2. 28 days as a cycle.
The time required to reach peak concentration after administration.
Cohort 1: pre-dose on Day 1, 14, 28 of Cycle 1, Day 14, 28 of Cycle 2. 2, 3, 4, 10, 24 hours after dose on Cycle1 Day28. Cohort 2: pre-dose, 2, 3, 4, 10, 24 hours after dose on Day 1, 28 of Cycle 1. Pre-dose on Day 14, 28 of Cycle2. 28 days as a cycle.
Peak concentration (Cmax)
Time Frame: Cohort 1: pre-dose on Day 1, 14, 28 of Cycle 1, Day 14, 28 of Cycle 2. 2, 3, 4, 10, 24 hours after dose on Cycle1 Day28. Cohort 2: pre-dose, 2, 3, 4, 10, 24 hours after dose on Day 1, 28 of Cycle 1. Pre-dose on Day 14, 28 of Cycle2. 28 days as a cycle.
the maximum plasma concentration of the drug after administration.
Cohort 1: pre-dose on Day 1, 14, 28 of Cycle 1, Day 14, 28 of Cycle 2. 2, 3, 4, 10, 24 hours after dose on Cycle1 Day28. Cohort 2: pre-dose, 2, 3, 4, 10, 24 hours after dose on Day 1, 28 of Cycle 1. Pre-dose on Day 14, 28 of Cycle2. 28 days as a cycle.
Area under blood concentration-time curve (AUC 0-24h)
Time Frame: Cohort 1: pre-dose on Day 1, 14, 28 of Cycle 1, Day 14, 28 of Cycle 2. 2, 3, 4, 10, 24 hours after dose on Cycle1 Day28. Cohort 2: pre-dose, 2, 3, 4, 10, 24 hours after dose on Day 1, 28 of Cycle 1. Pre-dose on Day 14, 28 of Cycle2. 28 days as a cycle.
The area surrounded by the blood concentration curve to the time axis.
Cohort 1: pre-dose on Day 1, 14, 28 of Cycle 1, Day 14, 28 of Cycle 2. 2, 3, 4, 10, 24 hours after dose on Cycle1 Day28. Cohort 2: pre-dose, 2, 3, 4, 10, 24 hours after dose on Day 1, 28 of Cycle 1. Pre-dose on Day 14, 28 of Cycle2. 28 days as a cycle.
Steady-state apparent volume of distribution (Vz/F)
Time Frame: Cohort 1: pre-dose on Day 1, 14, 28 of Cycle 1, Day 14, 28 of Cycle 2. 2, 3, 4, 10, 24 hours after dose on Cycle1 Day28. Cohort 2: pre-dose, 2, 3, 4, 10, 24 hours after dose on Day 1, 28 of Cycle 1. Pre-dose on Day 14, 28 of Cycle2. 28 days as a cycle.
The volume of distribution at steady-state concentration.
Cohort 1: pre-dose on Day 1, 14, 28 of Cycle 1, Day 14, 28 of Cycle 2. 2, 3, 4, 10, 24 hours after dose on Cycle1 Day28. Cohort 2: pre-dose, 2, 3, 4, 10, 24 hours after dose on Day 1, 28 of Cycle 1. Pre-dose on Day 14, 28 of Cycle2. 28 days as a cycle.
Steady-state blood trough concentration (Cmin,ss)
Time Frame: Cohort 1: pre-dose on Day 1, 14, 28 of Cycle 1, Day 14, 28 of Cycle 2. 2, 3, 4, 10, 24 hours after dose on Cycle1 Day28. Cohort 2: pre-dose, 2, 3, 4, 10, 24 hours after dose on Day 1, 28 of Cycle 1. Pre-dose on Day 14, 28 of Cycle2. 28 days as a cycle.
the lowest concentration during dosing and is usually obtained from the initial moment after dosing to the lowest concentration before the next dosing when multiple dosing reaches steady-state.
Cohort 1: pre-dose on Day 1, 14, 28 of Cycle 1, Day 14, 28 of Cycle 2. 2, 3, 4, 10, 24 hours after dose on Cycle1 Day28. Cohort 2: pre-dose, 2, 3, 4, 10, 24 hours after dose on Day 1, 28 of Cycle 1. Pre-dose on Day 14, 28 of Cycle2. 28 days as a cycle.
Complete response (CR) rate
Time Frame: Up to 80 weeks
The proportion of patients with an optimal response of CR.
Up to 80 weeks
Complete response (CR) + Complete response with partial hematological recovery (CRh)
Time Frame: Up to 80 weeks
Proportion of patients with optimal response of CR and CRh
Up to 80 weeks
Transfusion-independent improvement
Time Frame: Up to 80 weeks
Proportion of transfusion-dependent patients at baseline who were removed from red blood cell (RBC) or platelet transfusion dependence after randomization.
Up to 80 weeks
CR+CRh duration
Time Frame: Up to 80 weeks
In all patients with an optimal response of CR or CRh, the time from the date when CR or CRh was first achieved to the date of first clearly documented disease progression / relapse / treatment failure or death, whichever occurs first.
Up to 80 weeks
CR duration
Time Frame: Up to 80 weeks
For all patients with an optimal response of CR, the time from the date when CR was first achieved to the first clearly documented date of disease progression/relapse/treatment failure or death, whichever occurs first.
Up to 80 weeks
Duration of response (DOR)
Time Frame: Up to 80 weeks
The time from the date of first remission to the date of first clearly documented disease progression/relapse/treatment failure or date of death in all patients with optimal response of CR, CR with incomplete blood count recovery(CRi), CR with incomplete platelet recovery (CRp), Morphologic Leukemia-free state (MLFS), or Partial Remission (PR), whichever occurs first.
Up to 80 weeks
Time to CR+CRh
Time Frame: Up to 80 weeks
Time from the date of first TQB3454 dose to the date of first CR or CRh in all patients with optimal response to CR or CRh.
Up to 80 weeks
Event-free survival (EFS)
Time Frame: Up to 80 weeks
The time from the date of the first dose TQB3454 tablet to the first clearly documented date of relapse after disease remission, disease progression/treatment failure, or death, whichever occurs first.
Up to 80 weeks
Overall survival (OS)
Time Frame: Up to 80 weeks
Time from the date of first dose of TQB3454 tablet to the date of death from any cause.
Up to 80 weeks
Functional Assessment of Chronic Illness (FACIT) fatigue Scale
Time Frame: Up to 80 weeks
Proportion of patients with a confirmed improvement of at least 3 points from baseline in FACit-Fatigue scale scores.
Up to 80 weeks
Quality of life score
Time Frame: Up to 80 weeks
Proportion of patients with a confirmed improvement of at least 10 points from baseline in their overall health as assessed by European organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30).
Up to 80 weeks
Overall response rate (ORR)
Time Frame: Up to 80 weeks
Proportion of patients with an optimal response of CR, marrow CR (mCR), PR, or Hematology improvement (HI).
Up to 80 weeks
Progression-free survival (PFS)
Time Frame: Up to 80 weeks
from the date of first dose of TQB3454 tablet to the time of first recorded disease progression assessed by the investigator or relapse after CR or death from any cause. Disease progression includes acute leukaemia transformation.
Up to 80 weeks
Leukemia-free survival
Time Frame: Up to 80 weeks
from the date of first dose of TQB3454 tablet to the time of >20% original cells in bone marrow/peripheral blood, or diagnosis of acute extramedullary leukemia, or death from any cause.
Up to 80 weeks
Correlation between 2-hydroxyglutaric acid (2-HG) and efficacy
Time Frame: Pre-dose (baseline). Pre-dose on Cycle 1 Day 14, Cycle 1 Day 28, Cycle 2 Day 28, Cycle 3 Day 28, Cycle 4 Day 28, Cycle 5 Day 28, Cycle 6 Day 28, 28 days as a cycle
Liquid chromatography-mass spectrometry (LC-MS/MS) was used to determine 2-HG in plasma and to analyze its correlation with efficacy.
Pre-dose (baseline). Pre-dose on Cycle 1 Day 14, Cycle 1 Day 28, Cycle 2 Day 28, Cycle 3 Day 28, Cycle 4 Day 28, Cycle 5 Day 28, Cycle 6 Day 28, 28 days as a cycle

Collaborators and Investigators

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

Sponsor

Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

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)

July 10, 2023

Primary Completion (Estimated)

June 1, 2025

Study Completion (Estimated)

December 1, 2025

Study Registration Dates

First Submitted

January 12, 2024

First Submitted That Met QC Criteria

January 12, 2024

First Posted (Estimated)

January 23, 2024

Study Record Updates

Last Update Posted (Estimated)

January 23, 2024

Last Update Submitted That Met QC Criteria

January 12, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TQB3454-Ib-01

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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