A Clinical Trial of TQB3455 Tablets in Patients With Hematological Malignancies

NCT06550713 | Recruiting Phase 1

• 1 other identifier: TQB3455-I-01
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 7

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).

Conditions

Acute Myeloid Leukemia (AML); Myelodysplastic Syndrome (MDS)

Outcome Measures

Primary Outcomes (3)

• Dose-limiting toxicity (DLT)

  Subjects appear the toxic reaction relate to the drug after treatment within 28 days.

  Baseline up to 28 days

• The maximum tolerated dose (MTD)

  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

  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 Outcomes (7)

• Overall survival (OS)

  U to 96 weeks

• Duration of Response (DOR)

  Up to 48 weeks

• Complete Remission Rate

  Up to 48 weeks

• 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

• 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

Study Arms (1)

TQB3455 tablet and Azacitidine for Injection

EXPERIMENTAL

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

Interventions

TQB3455 tablet+Azacitidine for Injection DRUG

TQB3455 is a selective IDH2 mutant enzyme inhibitor. Azacitidine for injection is a cytosine nucleoside drug that is used for demethylation therapy.

TQB3455 tablet and Azacitidine for Injection

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Chia Tai Tianqing Pharmaceutical Group Co., Ltd.: lead

Study Sites (7)

Peking University People's Hospital

Beijing, Beijing Municipality, 100044, China

RECRUITING

Peking University international Hospital

Beijing, Beijing Municipality, 102206, China

NOT YET RECRUITING

The Second Hospital of Hebei Medical University

Shijiazhuang, Hebei, 050000, China

NOT YET RECRUITING

Harbin The First Hospital

Harbin, Heilongjiang, 150010, China

NOT YET RECRUITING

Shanghai Sixth People's Hospital

Shanghai, Shanghai Municipality, 201306, China

NOT YET RECRUITING

West China Hospital of Sichuan University

Chengdu, Sichuan, 610041, China

NOT YET RECRUITING

People's Hospital of Tianjin

Tianjin, Tianjin Municipality, 300121, China

NOT YET RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

Injections

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Central Study Contacts

Hao Jiang, Master

CONTACT

13601164350; 2516735116@qq.com

Wenbing Duan, Master

CONTACT

yukinoice@yeah.net

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2022
• First Posted: August 13, 2024
• Study Start: October 22, 2019
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: August 13, 2024

Record last verified: 2024-08

Locations

CN (7)