A Randomized, Open-Label, Multicenter, Phase III Clinical Trial to Evaluate the Efficacy and Safety of TQB3909 Tablets Versus Investigator's Choice in the Treatment of Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 128
- 试验地点
- 2
- 主要终点
- Progression free survival (PFS) evaluated by an independent review committee (IRC)
研究概览
简要总结
To Evaluate the Efficacy and Safety of TQB3909 Tablets versus Investigator's Choice in the Treatment of Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The subject voluntarily agrees to participate in this study, signs the informed consent form, and is expected to be compliant.
- •Age: ≥18 years; ECOG PS score: 0-2; expected survival >3 months.
- •Subject population:
- •Patients with a confirmed diagnosis of CLL/SLL according to the diagnostic criteria of the revised 2018 iwCLL guidelines;
- •Meet at least one indication for treatment of CLL/SLL according to the revised 2018 iwCLL guidelines;
- •Have developed treatment intolerance during or after immunochemotherapy and BTK inhibitor therapy, or have failed to achieve PR or better response after adequate treatment, or have experienced disease progression. For patients assessed by the investigator as unfit for immunochemotherapy, they must have developed treatment intolerance during BTK inhibitor therapy, failed to achieve PR or better response after adequate treatment, or experienced disease progression after adequate treatment.
- •Adequate major organ function.
- •SLL patients must have measurable disease on CT/MRI.
- •Female subjects of childbearing potential must agree to use contraception (e.g., intrauterine device, contraceptive pills, or condoms) during the study and for 6 months after the last dose; serum pregnancy test must be negative within 7 days prior to enrollment, and must not be breastfeeding. Male subjects must agree to use contraception during the study and for 6 months after the last dose.
排除标准
- •Comorbidities and Medical History:
- •History of or concurrent other malignancies within 3 years prior to the first dose. The following two conditions are allowed: other malignancies treated with surgery alone and achieving continuous disease-free survival (DFS) of 5 years; cured cervical carcinoma in situ, non-melanoma skin cancer, and superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ), and T1 (tumor invading lamina propria)];
- •History of Richter's transformation or prolymphocytic leukemia (PLL);
- •Known lymphoma/leukemia involvement of the central nervous system (CNS);
- •Prior allogeneic hematopoietic stem cell transplantation;
- •Autologous hematopoietic stem cell transplantation within 3 months prior to the first dose;
- •Multiple factors affecting oral drug administration (e.g., inability to swallow, chronic diarrhea, bowel obstruction, etc.);
- •Active or uncontrolled autoimmune cytopenia despite low-dose glucocorticoid therapy (equivalent to prednisone 20 mg), including autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP);
- •Toxicity from any prior treatment that has not recovered to ≤ Grade 1 per CTCAE, excluding alopecia, neutrophil count, and platelet count;
- •Major surgical treatment or significant traumatic injury within 28 days prior to the start of study treatment;
- •Severe arterial/venous thromboembolic events within 3 months prior to the first dose, such as cerebrovascular accidents (including transient ischemic attack, intracranial hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism, etc.;
- •History of psychoactive substance abuse that cannot be discontinued, or psychiatric disorders;
- •Subjects with any severe and/or uncontrolled diseases, including:
- •Myocardial ischemia or myocardial infarction ≥ Grade 2, arrhythmia (QTcF >450 ms for males, QTcF >470 ms for females), and ≥ Grade 2 congestive heart failure (New York Heart Association [NYHA] classification), or left ventricular ejection fraction (LVEF) <50% by echocardiography within 6 months prior to the first dose; Active infection (≥ Grade 2 infection per CTCAE); Active hepatitis*; Hepatitis B: HBV DNA ≥ lower limit of detection; Hepatitis C: HCV antibody positive and HCV viral titer > lower limit of detection; History of immunodeficiency, including HIV positivity or other acquired or congenital immunodeficiency diseases, or history of organ transplantation; Epilepsy requiring treatment;
- •Tumor-Related Symptoms and Treatment:
- •Chemotherapy, monoclonal antibody therapy, or radiotherapy within 4 weeks prior to the first dose; immune checkpoint inhibitors or CAR-T therapy within 12 weeks prior to the first dose; other small-molecule anti-tumor therapies within 5 half-lives (calculated from the end date of the last treatment);
- •Corticosteroids administered for anti-tumor purposes; short-term (≤7 days) systemic corticosteroid therapy (≤20 mg prednisone equivalent) to control lymphoma-related symptoms or BTKi withdrawal symptoms prior to enrollment is permitted, but tapering to discontinuation within 5 days after study start is required;
- •Prior treatment with BCL-2 inhibitors;
- •Retreatment with bendamustine is allowed if the prior response to bendamustine lasted >24 months;
- •Study Treatment-Related: Vaccination within 4 weeks prior to the first dose, or planned vaccination during the study;
- •Participation in other anti-tumor drug clinical trials within 4 weeks prior to the first dose; for small-molecule targeted drugs with defined targets such as BTK inhibitors, calculated as 5 half-lives;
- •Subjects with concomitant diseases that seriously endanger subject safety or affect study completion, or subjects considered unsuitable for enrollment for other reasons, as judged by the investigator;
- •Allergy to both allopurinol and benzbromarone.
研究组 & 干预措施
TQB3909 Tablets
The drug was administered every day for 28 consecutive days in a treatment cycle
干预措施: TQB3909 Tablets (Drug)
BR Regimen Bendamustine injection+ Rituximab or R2 Lenalidomide Capsules + Rituximab injection
BR Regimen Bendamustine Hydrochloride for Injection: 70 mg/m², intravenous (IV) administration on Days 1-2 of each cycle. IV infusion over 60-120 minutes.
Rituximab Injection: Intravenous administration at 375 mg/m² on Day 1 of Cycle 1, and at 500 mg/m² on Day 1 of Cycles 2-6.
R2 Regimen Lenalidomide Capsules: 10 mg/day, orally starting from Day 9 of Cycle 1. Each cycle consists of 28 days.
Rituximab Injection: 375 mg/m², intravenous (IV) administration on Days 1, 8, 15, and 22 of Cycle 1, followed by 375 mg/m² on Day 1 of Cycles 3-12. Each cycle consists of 28 days.
干预措施: Lenalidomide Capsules (Drug)
BR Regimen Bendamustine injection+ Rituximab or R2 Lenalidomide Capsules + Rituximab injection
BR Regimen Bendamustine Hydrochloride for Injection: 70 mg/m², intravenous (IV) administration on Days 1-2 of each cycle. IV infusion over 60-120 minutes.
Rituximab Injection: Intravenous administration at 375 mg/m² on Day 1 of Cycle 1, and at 500 mg/m² on Day 1 of Cycles 2-6.
R2 Regimen Lenalidomide Capsules: 10 mg/day, orally starting from Day 9 of Cycle 1. Each cycle consists of 28 days.
Rituximab Injection: 375 mg/m², intravenous (IV) administration on Days 1, 8, 15, and 22 of Cycle 1, followed by 375 mg/m² on Day 1 of Cycles 3-12. Each cycle consists of 28 days.
干预措施: Bendamustine Injection (Drug)
BR Regimen Bendamustine injection+ Rituximab or R2 Lenalidomide Capsules + Rituximab injection
BR Regimen Bendamustine Hydrochloride for Injection: 70 mg/m², intravenous (IV) administration on Days 1-2 of each cycle. IV infusion over 60-120 minutes.
Rituximab Injection: Intravenous administration at 375 mg/m² on Day 1 of Cycle 1, and at 500 mg/m² on Day 1 of Cycles 2-6.
R2 Regimen Lenalidomide Capsules: 10 mg/day, orally starting from Day 9 of Cycle 1. Each cycle consists of 28 days.
Rituximab Injection: 375 mg/m², intravenous (IV) administration on Days 1, 8, 15, and 22 of Cycle 1, followed by 375 mg/m² on Day 1 of Cycles 3-12. Each cycle consists of 28 days.
干预措施: Rituximab injection (Drug)
结局指标
主要结局
Progression free survival (PFS) evaluated by an independent review committee (IRC)
时间窗: Up to 4 years
Progression free survival (PFS) evaluated by an independent review committee (IRC)
次要结局
- Overall Survival (OS)(Up to 4 years)
- Progression free survival (PFS) evaluated by researchers(Up to 4 years)
- Objective response rate (ORR)(Up to 4 years)
- Duration of Response (DOR) per Independent Review Committee (IRC) and investigator assessment(Up to 4 years)