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) .

Chronic Lymphocytic Leukemia Clinical Trial

Official title:

A Phase Ib/II Clinical Trial on the Safety and Efficacy of TQB3909 Tablets in Patients With Recurrent or Refractory CLL/SLL.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05959694
• Other study ID #: TQB3909-Ib/II-02
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: October 11, 2023
• Est. completion date: June 2026

Study information

• Verified date: June 2023
• Source: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
• Contact: Jianyong Li, Doctor
• Phone: +86 13951877733
• Email: Ljianyonglm[@]mcdmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 107
• Est. completion date: June 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma
• Small Lymphocytic Lymphoma

Intervention

Drug:
• TQB3909 tablet
TQB3909 is an inhibitor targeting at B-cell lymphoma (BCL)-2 protein.

Locations

Country	Name	City	State
China	Anqing Municipal Hospital	Anqing	Anhui
China	Hunan Cancer Hospital	Changsha	Hunan
China	Peace Hospital Affiliated to Changzhi Medical College	Changzhi	Shanxi
China	Affiliated Hospital of Chengde Medical College	Chengde	Hebei
China	Sun Yat-Sen University Cancer Canter	Guangzhou	Guangdong
China	Harbin first hospital	Harbin	Heilongjiang
China	The Second Affiliated Hospital of Harbin Medical University	Harbin	Heilongjiang
China	Qilu Hospital of Shandong University	Jinan	Shandong
China	Linyi people's hospital	Linyi	Shandong
China	Affiliated hospital of southwest medical university	Luzhou	Sichuan
China	Mianyang Central Hospital	Mianyang	Sichuan
China	Jiangxi Cancer Hospital	Nanchang	Jiangxi
China	Jiangsu Provincial People's Hospital	Nanjing	Jiangsu
China	The First Affiliated Hospital of Ningbo University	Ningbo	Zhejiang
China	Shanghai Tongren Hospital	Shanghai	Shanghai
China	Shengjing Hospital Affiliated to China Medical University	Shenyang	Liaoning
China	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu
China	The Second Affiliated Hospital of Soochow University	Suzhou	Jiangsu
China	Tai 'an Central Hospital	Tai'an	Shandong
China	Tianjin Cancer Hospital	Tianjin	Tianjin
China	The First Affiliated Hospital of Xinjiang Medical University	Ürümqi	Xinjiang Uygur Autonomous Region
China	Gansu province Wuwei tumour hospital	Wuwei	Gansu
China	Affiliated Hospital of Xuzhou Medical University	Xuzhou	Jiangsu
China	Yibin Second People's Hospital	Yibin	Sichuan
China	Henan Cancer Hospital	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of adverse events (AE)	Incidence of AE evaluated by CTCAE 5.0 (Common Terminology Criteria for Adverse Events 5.0).	Up to 34 months.
Primary	Severity of adverse events (AE)	Severity of AE evaluated by CTCAE 5.0 (Common Terminology Criteria for Adverse Events 5.0).	Up to 34 months.
Primary	Incidence of serious adverse events (SAE)	Incidence of SAE evaluated by CTCAE 5.0 (Common Terminology Criteria for Adverse Events 5.0).	Up to 34 months.
Primary	Severity of serious adverse events (SAE)	Severity of SAE evaluated by CTCAE 5.0 (Common Terminology Criteria for Adverse Events 5.0).	Up to 34 months.
Primary	Incidence of abnormal laboratory examination indexes.	Incidence of abnormal laboratory examination indexes evaluated by CTCAE 5.0 (Common Terminology Criteria for Adverse Events 5.0).	Up to 34 months.
Primary	Severity of abnormal laboratory examination indexes.	Severity of abnormal laboratory examination indexes evaluated by CTCAE 5.0 (Common Terminology Criteria for Adverse Events 5.0).	Up to 34 months.
Primary	Recommended phase II dose (RP2D)	To determine the recommended phase II dose of TQB3909 tablets in the treatment of recurrent or refractory CLL/SLL.	Up to 18 months
Primary	Objective remission rate (ORR) determined by Independent Review Committee (IRC)	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).	Up to 34 months
Secondary	Objective remission rate (ORR) determined by the investigators' evaluation.	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).	Up to 34 months
Secondary	Duration of remission (DOR)	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).	Up to 34 months
Secondary	Time to disease progression (TTP)	Refers to the time from the first medication to the objective progress of the disease.	Up to 34 months
Secondary	Time to remission (TTR)	Time from the beginning of treatment to the first recording of remission (PR or better remission), only the remission population was analyzed.	Up to 34 months
Secondary	Progression-free survival (PFS)	The time from the first medication to the objective progression of the disease or death caused from any cause (whichever comes first).	Up to 34 months
Secondary	Overall survival (OS)	Time from first dose of study drug to date of death from any cause.	Up to 34 months
Secondary	Time to reach maximum concentration (Tmax)	Time to reach maximum plasma concentration after single and multiple dosing of TQB3909 tablets.	Within 120 hours after administration
Secondary	Maximum plasma drug concentration (Cmax)	Cmax is the maximum plasma concentration of TQB3909.	Within 120 hours after administration
Secondary	Area under the plasma concentration-time curve (AUC0-t)	To characterize the pharmacokinetics of TQB3909 by assessment of area under the plasma concentration time curve.	Within 120 hours after administration
Secondary	Plasma elimination half-life (t1/2)	t1/2 is time it takes for the blood concentration of TQB3909 to drop by half.	Within 120 hours after administration
Secondary	Undetectable measurable residual disease (U-MRD) ratio of peripheral blood and/or bone marrow.	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.	Up to 34 months
Secondary	Correlation between potential biomarkers and TQB3909 tablets.	Correlation of potential biomarkers with TQB3909 tablets: such as BTK and PLCG2 mutation status and allele frequency.	Up to 34 months