A Clinical Trial of TQB3455 Tablets in Patients With Hematological Malignancies

Official title

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

Overview

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).

Interventions

• 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.

Primary outcome measures

• Dose-limiting toxicity (DLT) [Time frame: Baseline up to 28 days]
• The maximum tolerated dose (MTD) [Time frame: Up to 48 weeks]
• Overall Remission Rate [Time frame: Up to 48 weeks]

Secondary outcome measures (7)

• Overall survival (OS) [Time frame: U to 96 weeks]
• Duration of Response (DOR) [Time frame: Up to 48 weeks]
• Complete Remission Rate [Time frame: 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]
• 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]
• 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]
• 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.]

Eligibility criteria

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:

• 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)
• 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)
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 7 centers

• Peking University People's Hospital — Beijing
• Peking University international Hospital — Beijing
• The Second Hospital of Hebei Medical University — Shijiazhuang
• Harbin The First Hospital — Harbin
• Shanghai Sixth People's Hospital — Shanghai
• West China Hospital of Sichuan University — Chengdu
• People's Hospital of Tianjin — Tianjin

Identifiers

NCT: NCT06550713 · TQB3455-I-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗