Clinical trial NCT05959694: 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) .
Official title: A Phase Ib/II Clinical Trial on the Safety and Efficacy of TQB3909 Tablets in Patients With Recurrent or Refractory CLL/SLL.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-07-25
Enrollment: 107
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of adverse events (AE)
timeFrame: Up to 34 months.
measure: Severity of adverse events (AE)
timeFrame: Up to 34 months.
measure: Incidence of serious adverse events (SAE)
timeFrame: Up to 34 months.
measure: Severity of serious adverse events (SAE)
timeFrame: Up to 34 months.
measure: Incidence of abnormal laboratory examination indexes.
timeFrame: Up to 34 months.
measure: Severity of abnormal laboratory examination indexes.
timeFrame: Up to 34 months.
measure: Recommended phase II dose (RP2D)
timeFrame: Up to 18 months
measure: Objective remission rate (ORR) determined by Independent Review Committee (IRC)
timeFrame: Up to 34 months
Secondary outcomes:
measure: Objective remission rate (ORR) determined by the investigators' evaluation.
timeFrame: Up to 34 months
measure: Duration of remission (DOR)
timeFrame: Up to 34 months
measure: Time to disease progression (TTP)
timeFrame: Up to 34 months
measure: Time to remission (TTR)
timeFrame: Up to 34 months
measure: Progression-free survival (PFS)
timeFrame: Up to 34 months
measure: Overall survival (OS)
timeFrame: Up to 34 months
measure: Time to reach maximum concentration (Tmax)
timeFrame: Within 120 hours after administration
measure: Maximum plasma drug concentration (Cmax)
timeFrame: Within 120 hours after administration
measure: Area under the plasma concentration-time curve (AUC0-t)
timeFrame: Within 120 hours after administration
measure: Plasma elimination half-life (t1/2)
timeFrame: Within 120 hours after administration
measure: Undetectable measurable residual disease (U-MRD) ratio of peripheral blood and/or bone marrow.
timeFrame: Up to 34 months
measure: Correlation between potential biomarkers and TQB3909 tablets.
timeFrame: Up to 34 months
Other outcomes:
Locations:
city: Anqing
country: China
facility: Anqing Municipal Hospital
state: Anhui
city: Wuwei
country: China
facility: Gansu province Wuwei tumour hospital
state: Gansu
city: Guangzhou
country: China
facility: Sun Yat-Sen University Cancer Canter
state: Guangdong
city: Chengde
country: China
facility: Affiliated Hospital of Chengde Medical College
state: Hebei
city: Harbin
country: China
facility: Harbin first hospital
state: Heilongjiang
city: Harbin
country: China
facility: The Second Affiliated Hospital of Harbin Medical University
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Nanjing
country: China
facility: Jiangsu Provincial People's Hospital
state: Jiangsu
city: Suzhou
country: China
facility: The Second Affiliated Hospital of Soochow University
state: Jiangsu
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
city: Xuzhou
country: China
facility: Affiliated Hospital of Xuzhou Medical University
state: Jiangsu
city: Nanchang
country: China
facility: Jiangxi Cancer Hospital
state: Jiangxi
city: Shenyang
country: China
facility: Shengjing Hospital Affiliated to China Medical University
state: Liaoning
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Linyi
country: China
facility: Linyi people's hospital
state: Shandong
city: Tai'an
country: China
facility: Tai 'an Central Hospital
state: Shandong
city: Shanghai
country: China
facility: Shanghai Tongren Hospital
state: Shanghai
city: Changzhi
country: China
facility: Peace Hospital Affiliated to Changzhi Medical College
state: Shanxi
city: Luzhou
country: China
facility: Affiliated hospital of southwest medical university
state: Sichuan
city: Mianyang
country: China
facility: Mianyang Central Hospital
state: Sichuan
city: Yibin
country: China
facility: Yibin Second People's Hospital
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Cancer Hospital
state: Tianjin
city: Ürümqi
country: China
facility: The First Affiliated Hospital of Xinjiang Medical University
state: Xinjiang Uygur Autonomous Region
city: Ningbo
country: China
facility: The First Affiliated Hospital of Ningbo University
state: Zhejiang
Study officials:
References: