A Clinical Trial of TQB3455 Tablets in Patients With Hematological Malignancies
- Conditions
- Acute Myeloid Leukemia (AML)Myelodysplastic Syndrome (MDS)
- Interventions
- Drug: TQB3455 tablet+Azacitidine for Injection
- Registration Number
- NCT06550713
- Lead Sponsor
- Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
- Brief Summary
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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 100
Patients meeting all of the following inclusion criteria can be included in this trial:
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Age ≥ 18 years old;
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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:
- Difficult to treat or recurrent (>5% of primitive cells reappear in the bone marrow after complete remission) AML; (Single drug group)
- Newly diagnosed AML subjects recognized by researchers as unable to receive standard treatment due to age, physical condition, or risk factors; (Joint group)
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MDS subjects belong to the following prognostic risk categories according to the revised International Prognostic Scoring System (IPSS-R):
- Extremely high-risk (>6 points)
- High risk (>4.5 points - ≤ 6 points)
- Medium risk (>3 points - ≤ 4.5 points)
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Clearly indicating the presence of IDH2 gene mutation;
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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;
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Serum total bilirubin ≤ 1.5 × ULN (for Gilbert syndrome subjects, bilirubin ≤ 3 × ULN);
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Renal function: serum creatinine ≤ 1.5 × ULN or creatinine clearance rate ≥ 50ml/min;
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Recovery of toxic reactions caused by surgery, radiation therapy, or other anti-tumor treatments to ≤ Grade I;
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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;
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The subjects voluntarily joined this study.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description TQB3455 tablet and Azacitidine for Injection TQB3455 tablet+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.
- Primary Outcome Measures
Name Time Method Dose-limiting toxicity (DLT) Baseline up to 28 days Subjects appear the toxic reaction relate to the drug after treatment within 28 days.
The maximum tolerated dose (MTD) Up to 48 weeks The highest dose at which no more than 33% of the subjects experience a dose-limiting toxicity (DLT) during treatment.
Overall Remission Rate 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.
- Secondary Outcome Measures
Name Time Method Overall survival (OS) U to 96 weeks Overall survival defined as the time from enrollment to death from any cause.
Duration of Response (DOR) 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.
α-Hydroxyglutaric acid (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. The concentration of 2-HG.
Complete Remission Rate 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).
Cmax 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).
Tmax 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.
Area Under the Curve (AUC) 0-t 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.
Trial Locations
- Locations (7)
Peking University People's Hospital
🇨🇳Beijing, Beijing, China
Peking University international Hospital
🇨🇳Beijing, Beijing, China
The Second Hospital of Hebei Medical University
🇨🇳Shijiazhuang, Hebei, China
Harbin The First Hospital
🇨🇳Harbin, Heilongjiang, China
Shanghai Sixth People's Hospital
🇨🇳Shanghai, Shanghai, China
People's Hospital of Tianjin
🇨🇳Tianjin, Tianjin, China
West China Hospital of Sichuan University
🇨🇳Chengdu, Sichuan, China