A Clinical Trial of TQB3455 Tablets in Patients With Hematological Malignancies

August 8, 2024 updated by: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Phase I Clinical Trial Protocol for Tolerability and Pharmacokinetics of TQB3455 Tablets in Patients With Hematological Malignancies

This study is a clinical trial to evaluate the tolerability and pharmacokinetics of TQB3455 tablets in patients with hematological malignancies. TQB3455 is an isocitrate dehydrogenase 2(IDH2) inhibitor . This project is divided into two stages. The first stage aims to evaluate the safety and tolerability of single or multiple oral administration of TQB3455 tablets in subjects with malignant hematological tumors. The second phase aims to evaluate the efficacy and safety of TQB3455 tablets alone or in combination with azacitidine in subjects with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

100

Phase

  • 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 Contact Backup

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100044
        • Recruiting
        • Peking University People's Hospital
        • Contact:
      • Beijing, Beijing, China, 102206
        • Not yet recruiting
        • Peking University International Hospital
        • Contact:
    • Hebei
      • Shijiazhuang, Hebei, China, 050000
        • Not yet recruiting
        • The Second Hospital of Hebei Medical University
        • Contact:
        • Contact:
    • Heilongjiang
      • Harbin, Heilongjiang, China, 150010
        • Not yet recruiting
        • Harbin The First Hospital
        • Contact:
          • Tiejun Gong, Master
          • Phone Number: 13836027737
          • Email: arc@sina.con
    • Shanghai
      • Shanghai, Shanghai, China, 201306
        • Not yet recruiting
        • Shanghai Sixth People's Hospital
        • Contact:
    • Sichuan
      • Chengdu, Sichuan, China, 610041
        • Not yet recruiting
        • West China Hospital of Sichuan University
        • Contact:
    • Tianjin
      • Tianjin, Tianjin, China, 300121
        • Not yet recruiting
        • People's Hospital of Tianjin
        • 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 meeting all of the following inclusion criteria can be included in this trial:

  • Age ≥ 18 years old;

  • According to the World Health Organization (WHO) classification, subjects diagnosed with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) should meet one of the following criteria:

    1. Difficult to treat or recurrent (>5% of primitive cells reappear in the bone marrow after complete remission) AML; (Single drug group)
    2. Newly diagnosed AML subjects recognized by researchers as unable to receive standard treatment due to age, physical condition, or risk factors; (Joint group)

  • MDS subjects belong to the following prognostic risk categories according to the revised International Prognostic Scoring System (IPSS-R):

    1. Extremely high-risk (>6 points)
    2. High risk (>4.5 points - ≤ 6 points)
    3. Medium risk (>3 points - ≤ 4.5 points)
  • Clearly indicating the presence of IDH2 gene mutation;
  • Blood platelet (PLT) ≥20×10^9/L； Or subjects with PLT<20 × 10^9/L, but recognized by the researchers as being caused by tumor reasons;
  • Serum total bilirubin ≤ 1.5 × ULN (for Gilbert syndrome subjects, bilirubin ≤ 3 × ULN);
  • Renal function: serum creatinine ≤ 1.5 × ULN or creatinine clearance rate ≥ 50ml/min;
  • Recovery of toxic reactions caused by surgery, radiation therapy, or other anti-tumor treatments to ≤ Grade I;
  • Women should agree to use contraceptive measures during the study period and within 6 months after the end of the study; Male participants must agree to use contraception during the study period and within 6 months after the end of the study period;
  • The subjects voluntarily joined this study.

Exclusion Criteria:

  • Subjects who experience relapse after bone marrow transplantation;
  • Subjects who have received systemic anti-tumor therapy or radiation therapy within 3 weeks prior to the use of the investigational drug;
  • Individuals who have participated in clinical trials of other drugs within the four weeks prior to using the investigational drug;
  • Individuals with multiple factors that affect oral medication, such as inability to swallow, post gastrointestinal resection, chronic diarrhea, and intestinal obstruction;
  • Subjects who have previously used targeted isocitrate dehydrogenase 2 (IDH2) inhibitors;
  • The subject has uncontrolled systemic fungal, bacterial, or viral infections;
  • High blood pressure subjects who are still poorly controlled despite drug treatment;
  • Obvious cardiovascular diseases, such as heart failure classified as grade 2 or above by the New York Heart Association (NYHA), unstable angina in the past 3 months, myocardial ischemia or infarction, arrhythmia and grade I heart failure, or the presence of other factors at risk of prolonging the QT interval (such as arrhythmia, hypokalemia ≥ grade 3, family history of long QT interval);
  • Severe leukemia complications that endanger life, such as uncontrolled bleeding, hypoxia or shock pneumonia, disseminated intravascular coagulation;
  • Subjects known to have central nervous system leukemia or clinical symptoms of central nervous system leukemia;
  • Individuals with a history of abuse of psychotropic drugs who are unable to quit or have mental disorders;
  • Subjects with active replication of hepatitis B virus and hepatitis C virus;
  • Individuals with a history of immunodeficiency, including HIV positive or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation;
  • According to the researcher's judgment, there are accompanying diseases that pose a serious threat to the safety of the subjects or affect their ability to complete the study.

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: TQB3455 tablet and Azacitidine for Injection

Stage1：TQB3455 tablet, oral, once a day, for 28 consecutive days as a treatment cycle.

Stage2：TQB3455 tablet, oral, once a day, for 28 consecutive days as a treatment cycle.

Azacitidine for injection: A treatment cycle of 4 weeks, with subcutaneous injection of Azacitidine standard dose on the first to seventh day of each cycle.
Drug: TQB3455 tablet+Azacitidine for Injection
TQB3455 is a selective IDH2 mutant enzyme inhibitor. Azacitidine for injection is a cytosine nucleoside drug that is used for demethylation therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose-limiting toxicity (DLT)
Time Frame: Baseline up to 28 days
Subjects appear the toxic reaction relate to the drug after treatment within 28 days.
Baseline up to 28 days
The maximum tolerated dose (MTD)
Time Frame: Up to 48 weeks
The highest dose at which no more than 33% of the subjects experience a dose-limiting toxicity (DLT) during treatment.
Up to 48 weeks
Overall Remission Rate
Time Frame: Up to 48 weeks
The number of participants with CR + incomplete recovery (CRi) + incomplete platelet recovery (CRp) according to modified International Working Group Acute Myeloid Leukemia (IWG AML) response criteria.
Up to 48 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of Response (DOR)
Time Frame: Up to 48 weeks
DOR will be defined as median number of months from date of first documented objective response until first documented sign of disease progression or death due to any causes.
Up to 48 weeks
Overall survival (OS)
Time Frame: U to 96 weeks
Overall survival defined as the time from enrollment to death from any cause.
U to 96 weeks
Complete Remission Rate
Time Frame: Up to 48 weeks
The number of participants with morphologic complete remission (CR) according to modified International Working Group Acute Myeloid Leukemia Response Criteria (IWG AML).
Up to 48 weeks
Cmax
Time Frame: Hour 0, 0.25, 0.5, 1, 2, 3, 5, 8, 10, 12, 24, 48, 96, 144 hours post-dose on single dose; Hour 0 of day 8, day 15, day 22 on multiple dose and hour 0, 0.25, 0.5, 1, 2, 3, 5, 8, 12, 24 hours post-dose on multiple dose of day 28
Cmax is the maximum plasma concentration of TQB3455 or metabolite(s).
Hour 0, 0.25, 0.5, 1, 2, 3, 5, 8, 10, 12, 24, 48, 96, 144 hours post-dose on single dose; Hour 0 of day 8, day 15, day 22 on multiple dose and hour 0, 0.25, 0.5, 1, 2, 3, 5, 8, 12, 24 hours post-dose on multiple dose of day 28
Tmax
Time Frame: Hour 0, 0.25, 0.5, 1, 2, 3, 5, 8, 10, 12, 24, 48, 96, 144 hours post-dose on single dose; Hour 0 of day 8, day 15, day 22 on multiple dose and hour 0, 0.25, 0.5, 1, 2, 3, 5, 8, 12, 24 hours post-dose on multiple dose of day 28
To characterize the pharmacokinetics of TQB3455 by assessment of time to reach maximum plasma concentration.
Hour 0, 0.25, 0.5, 1, 2, 3, 5, 8, 10, 12, 24, 48, 96, 144 hours post-dose on single dose; Hour 0 of day 8, day 15, day 22 on multiple dose and hour 0, 0.25, 0.5, 1, 2, 3, 5, 8, 12, 24 hours post-dose on multiple dose of day 28
Area Under the Curve (AUC) 0-t
Time Frame: Hour 0, 0.25, 0.5, 1, 2, 3, 5, 8, 10, 12, 24, 48, 96, 144 hours post-dose on single dose; Hour 0 of day 8, day 15, day 22 on multiple dose and hour 0,0.25, 0.5, 1, 2, 3, 5, 8, 12, 24 hours post-dose on multiple dose of day 28
To characterize the pharmacokinetics of TQB3455 by assessment of area under the plasma concentration time curve from zero to infinity.
Hour 0, 0.25, 0.5, 1, 2, 3, 5, 8, 10, 12, 24, 48, 96, 144 hours post-dose on single dose; Hour 0 of day 8, day 15, day 22 on multiple dose and hour 0,0.25, 0.5, 1, 2, 3, 5, 8, 12, 24 hours post-dose on multiple dose of day 28
α-Hydroxyglutaric acid (2-HG)
Time Frame: Day 1, Day 8 and Day 15 pre-dose on cycle 1; Day1, Day15 pre-dose on cycle 2 ; Day 1 pre-dose on multiple dose from cycle 3 to cycle 8. Each cycle is 28 days.
The concentration of 2-HG.
Day 1, Day 8 and Day 15 pre-dose on cycle 1; Day1, Day15 pre-dose on cycle 2 ; Day 1 pre-dose on multiple dose from cycle 3 to cycle 8. Each cycle is 28 days.

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)

October 22, 2019

Primary Completion (Estimated)

December 1, 2025

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

July 25, 2022

First Submitted That Met QC Criteria

August 8, 2024

First Posted (Actual)

August 13, 2024

Study Record Updates

Last Update Posted (Actual)

August 13, 2024

Last Update Submitted That Met QC Criteria

August 8, 2024

Last Verified

August 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TQB3455-I-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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