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A Clinical Trial on the Safety and Efficacy of TQB3909 Tablets in Patients With Recurrent or Refractory Chronic Lymphocytic Leukemia (CLL) /Small Lymphocytic Lymphoma (SLL) .

Phase 1
Recruiting
Conditions
Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Interventions
Drug: TQB3909 tablet
Registration Number
NCT05959694
Lead Sponsor
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Brief Summary

This is a phase Ib/II clinical trial to evaluate the safety and efficacy of TQB3909 tablets in patients with recurrent or refractory CLL/SLL.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
107
Inclusion Criteria
  • The subjects volunteered to join the study and signed informed consent form (ICF) with good compliance;
  • Age: ≥ 18 years old, ≤75 years old (when signing ICF); Eastern Cooperative Oncology Group Performance Status (ECOG PS) score: 0-1; The expected survival period is more than 3 months;
  • Subjects: patients diagnosed as CLL/SLL according to the revised diagnostic criteria of 2018 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines;
  • Computed Tomography / Magnetic Resonance Imaging (CT/MRI) of patients with SLL showed measurable lesions;
  • Female subjects of childbearing age should agree to use contraceptive measures (such as intrauterine devices, contraceptives or condoms) during the study period and within 6 months after the end of the study; serum pregnancy/urine pregnancy test within 7 days before study enrollment;
Exclusion Criteria
  • Complicated diseases and medical history:

    1. It has appeared or is currently suffering from other malignant tumors within 3 years before the first medication. The following two situations can be included in the group: other malignant tumors treated by single surgery have achieved disease-free survival (DFS) for five consecutive years; Cured cervical carcinoma in situ, non-melanoma skin cancer and superficial bladder tumor [Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor infiltrating basement membrane)];
    2. Lymphoma/leukemia is known to involve the central nervous system (CNS);
    3. Previously received allogeneic hematopoietic stem cell transplantation;
    4. Received autologous hematopoietic stem cell transplantation within 3 months before the first medication;
    5. Unresolved toxic reaction ≥ CTCAE grade 1 caused by any previous treatment;
    6. Arterial/venous thrombotic events occurred within 6 months before the first medication, such as cerebrovascular accidents (including transient ischemic attack, cerebral hemorrhage and cerebral infarction), deep venous thrombosis and pulmonary embolism;
    7. Subjects with any serious and/or uncontrollable diseases;
  • Tumor-related symptoms and treatment:

    1. He has received chemotherapy and radiotherapy within 4 weeks before the first medication, immune checkpoint inhibitor and Chimeric Antigen Receptor T (CAR-T)-Cell Immunotherapy within 12 weeks before the first medication, and other small molecule anti-tumor treatments (the elution period is calculated from the end of the last treatment) before the first medication are within 5 half-lives;
    2. previously received BCL-2 inhibitors;
  • Research-related treatment: received the vaccine within 4 weeks before the first medication, or planned to be vaccinated during the study;

  • Participated in clinical trials of other antineoplastic drugs within 4 weeks before the first medication;

  • According to the investigators' judgment, there are patients with accompanying diseases that seriously endanger the safety of the subjects or affect the completion of the study, or subjects who think that there are other reasons that are not suitable for inclusion.

  • Allergic to allopurinol and benzbromarone.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
TQB3909 tabletsTQB3909 tabletOral administration, 400mg or 600 mg, once a day, and 28 days is a treatment cycle. Continue medication until the disease progresses or intolerant toxicity appears.
Primary Outcome Measures
NameTimeMethod
Incidence of adverse events (AE)Up to 34 months.

Incidence of AE evaluated by CTCAE 5.0 (Common Terminology Criteria for Adverse Events 5.0).

Severity of adverse events (AE)Up to 34 months.

Severity of AE evaluated by CTCAE 5.0 (Common Terminology Criteria for Adverse Events 5.0).

Incidence of serious adverse events (SAE)Up to 34 months.

Incidence of SAE evaluated by CTCAE 5.0 (Common Terminology Criteria for Adverse Events 5.0).

Severity of serious adverse events (SAE)Up to 34 months.

Severity of SAE evaluated by CTCAE 5.0 (Common Terminology Criteria for Adverse Events 5.0).

Incidence of abnormal laboratory examination indexes.Up to 34 months.

Incidence of abnormal laboratory examination indexes evaluated by CTCAE 5.0 (Common Terminology Criteria for Adverse Events 5.0).

Severity of abnormal laboratory examination indexes.Up to 34 months.

Severity of abnormal laboratory examination indexes evaluated by CTCAE 5.0 (Common Terminology Criteria for Adverse Events 5.0).

Recommended phase II dose (RP2D)Up to 18 months

To determine the recommended phase II dose of TQB3909 tablets in the treatment of recurrent or refractory CLL/SLL.

Objective remission rate (ORR) determined by Independent Review Committee (IRC)Up to 34 months

Determine the objective remission rate (ORR) based on the evaluation results of the Independent Review Committee (IRC), defined as the proportion of subjects whose best remission is complete remission (CR) and partial remission (PR).

Secondary Outcome Measures
NameTimeMethod
Progression-free survival (PFS)Up to 34 months

The time from the first medication to the objective progression of the disease or death caused from any cause (whichever comes first).

Time to remission (TTR)Up to 34 months

Time from the beginning of treatment to the first recording of remission (PR or better remission), only the remission population was analyzed.

Time to reach maximum concentration (Tmax)Within 120 hours after administration

Time to reach maximum plasma concentration after single and multiple dosing of TQB3909 tablets.

Objective remission rate (ORR) determined by the investigators' evaluation.Up to 34 months

The objective remission rate (ORR) was determined by the results of the investigator s' evaluation, defined as the proportion of subjects whose best remission is complete remission (CR) and partial remission (PR).

Duration of remission (DOR)Up to 34 months

For all subjects whose best response was PR, CR,, the time from the date of first achieving PR, CR to the date of first definite disease progression or death from any cause (whichever occurs first).

Time to disease progression (TTP)Up to 34 months

Refers to the time from the first medication to the objective progress of the disease.

Overall survival (OS)Up to 34 months

Time from first dose of study drug to date of death from any cause.

Maximum plasma drug concentration (Cmax)Within 120 hours after administration

Cmax is the maximum plasma concentration of TQB3909.

Area under the plasma concentration-time curve (AUC0-t)Within 120 hours after administration

To characterize the pharmacokinetics of TQB3909 by assessment of area under the plasma concentration time curve.

Plasma elimination half-life (t1/2)Within 120 hours after administration

t1/2 is time it takes for the blood concentration of TQB3909 to drop by half.

Undetectable measurable residual disease (U-MRD) ratio of peripheral blood and/or bone marrow.Up to 34 months

Refers to the undetected residual lesions. Peripheral blood and/or bone marrow are used to detect less than 1 CLL cell (less than 10-4) in 10000 white blood cells by flow cytometry.

Correlation between potential biomarkers and TQB3909 tablets.Up to 34 months

Correlation of potential biomarkers with TQB3909 tablets: such as BTK and PLCG2 mutation status and allele frequency.

Trial Locations

Locations (25)

Anqing Municipal Hospital

🇨🇳

Anqing, Anhui, China

Gansu province Wuwei tumour hospital

🇨🇳

Wuwei, Gansu, China

Qilu Hospital of Shandong University

🇨🇳

Jinan, Shandong, China

Affiliated Hospital of Chengde Medical College

🇨🇳

Chengde, Hebei, China

The Second Affiliated Hospital of Harbin Medical University

🇨🇳

Harbin, Heilongjiang, China

Henan Cancer Hospital

🇨🇳

Zhengzhou, Henan, China

Jiangsu Provincial People's Hospital

🇨🇳

Nanjing, Jiangsu, China

Tai 'an Central Hospital

🇨🇳

Tai'an, Shandong, China

Peace Hospital Affiliated to Changzhi Medical College

🇨🇳

Changzhi, Shanxi, China

The First Affiliated Hospital of Xinjiang Medical University

🇨🇳

Ürümqi, Xinjiang Uygur Autonomous Region, China

The Second Affiliated Hospital of Soochow University

🇨🇳

Suzhou, Jiangsu, China

Sun Yat-Sen University Cancer Canter

🇨🇳

Guangzhou, Guangdong, China

Harbin first hospital

🇨🇳

Harbin, Heilongjiang, China

Hunan Cancer Hospital

🇨🇳

Changsha, Hunan, China

Affiliated Hospital of Xuzhou Medical University

🇨🇳

Xuzhou, Jiangsu, China

The First Affiliated Hospital of Soochow University

🇨🇳

Suzhou, Jiangsu, China

Jiangxi Cancer Hospital

🇨🇳

Nanchang, Jiangxi, China

Linyi people's hospital

🇨🇳

Linyi, Shandong, China

Shengjing Hospital Affiliated to China Medical University

🇨🇳

Shenyang, Liaoning, China

Mianyang Central Hospital

🇨🇳

Mianyang, Sichuan, China

Shanghai Tongren Hospital

🇨🇳

Shanghai, Shanghai, China

Affiliated hospital of southwest medical university

🇨🇳

Luzhou, Sichuan, China

The First Affiliated Hospital of Ningbo University

🇨🇳

Ningbo, Zhejiang, China

Yibin Second People's Hospital

🇨🇳

Yibin, Sichuan, China

Tianjin Cancer Hospital

🇨🇳

Tianjin, Tianjin, China

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