A Multi-center Clinical Study of Zanubrutinib in Combination With First-line Chemoimmunotherapy in Patients With Grade 3A High-risk Follicular Lymphoma
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 37
- 试验地点
- 1
- 主要终点
- CR
研究概览
简要总结
Background： At present, there is controversy about whether FL3a is treated as FL or DLBCL. Relevant studies have shown that compared with patients with FL3a grade 1~2, they have unique immunohistochemical characteristics, and there are some differences in clinical features and outcomes. In patients with FL3a, the Ki-67 index is higher, the recurrence rate is higher, there is more histologic transformation, the prognosis is worse, and the likelihood of lymphoma-related death is higher. Bruton's tyrosine kinase (BTK) is a key kinase in the B-cell signaling pathway, and studies have shown that BTK inhibitors including zanubrutinib combined with traditional immunochemotherapy regimens may have a synergistic effect in the treatment of B-cell malignancies, and the combination has become one of the current clinical research directions.
Aim:
To assess the efficacy and safety of zanubrutinib in combination with first-line immunochemotherapy in high-risk patients with FL3a.
详细描述
Bruton's tyrosine kinase (BTK) is a key kinase in the B-cell signaling pathway, and its abnormal activation leads to abnormal activation of the B-cell receptor signaling pathway, B-cell malignant proliferation, and lymphoma.
There is controversy about whether FL3a is treated as FL or DLBCL. Relevant studies have shown that compared with patients with FL3a grade 1~2, they have unique immunohistochemical characteristics, and there are some differences in clinical features and outcomes. In patients with FL3a, the Ki-67 index is higher, the recurrence rate is higher, there is more histologic transformation, the prognosis is worse, and the likelihood of lymphoma-related death is higher. Bruton's tyrosine kinase (BTK) is a key kinase in the B-cell signaling pathway, and studies have shown that BTK inhibitors including zanubrutinib combined with traditional immunochemotherapy regimens may have a synergistic effect in the treatment of B-cell malignancies, and the combination has become one of the current clinical research directions.
The recent study is to assess the efficacy and safety of zanubrutinib in combination with first-line immunochemotherapy in high-risk patients with FL3a.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age 18-70 years old (including 18 years old and 70 years old), ECOG score 0-2 points;
- •Confirmed diagnosis of follicular lymphoma with pathological grade of 3A (pathological report of three months before enrollment is acceptable) (Note: If there is any doubt about the pathological diagnosis, a domestic third-party consultation can be organized);
- •Treatment-naïve patients with indications for treatment;
- •Meet at least one of the criteria for high tumor burden in GELF;
- •Have not received other tumor-related treatments in the past;
- •Acceptable hematological indexes, no contraindications to chemotherapy;
- •Liver function: TBIL≤1.5×ULN; ALT or AST ≤2.5×ULN; Alkaline phosphatase ≤3×ULN in patients with non-bone invasion;
- •Renal function: serum creatinine ≤1.5×ULN;
- •Female and male patients of childbearing potential and their spouses are willing to use adequate contraception throughout the study period, and female patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to the first dose;
- •Subjects voluntarily participated in the clinical trial, signed the informed consent form, and cooperated with the follow-up.
排除标准
- •Refusal to collect blood specimens;
- •Previous allergy to any of the medications in the regimen;
- •Pregnant and lactating women;
- •Significant illness that, in the opinion of the investigator, can cause trial interference;
- •Combined with other tumors;
- •Presence of contraindications related to the treatment of the drug in the protocol;
- •Those with severe mental illness;
- •Participating in other clinical trials;
- •Prior treatment with anti-tumor therapy (such as radiotherapy, chemotherapy, hormonal therapy, biological therapy, immunotherapy);
- •Other serious diseases that may limit the subject's participation in this trial, such as: uncontrolled diabetes mellitus; Severe cardiac insufficiency (NYHA classification II or above); Acute coronary syndrome within the past 6 months; Coronary revascularization such as stenting, coronary artery bypass surgery, and other heart and large vessel related surgeries in the past 6 months; Severe arrhythmias include frequent premature ventricular episodes, ventricular tachycardia, rapid atrial fibrillation/atrial flutter, and severe bradycardia. Uncontrolled hypertension: systolic blood pressure > 150 mmHg, diastolic blood pressure > 100 mmHg. Gastric ulcer (gastric ulcer judged by the investigator to be at risk of perforation); Active autoimmune disease (e.g., systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjögren's syndrome, autoimmune thrombocytopenia, etc.); Severe respiratory diseases (such as obstructive pulmonary disease and history of bronchospasm), etc.;
- •In the opinion of the investigators, it is not suitable for enrollment;
- •Hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA titer test is not within the normal reference value; Those who are positive for hepatitis C virus (HCV) antibody and positive for hepatitis C virus (HCV) RNA in peripheral blood; Those who are positive for human immunodeficiency virus (HIV) antibodies; Those who test positive for syphilis.
结局指标
主要结局
CR
时间窗: 2 years
complete response
次要结局
- OS of 2 years(2 years)
- ORR(2 years)
- PFS of 2 years(2 years)