Clinical Study on the Efficacy and Safety of Zanubrutinib Combined With Chemotherapy for Continuous Maintenance Treatment of Newly Diagnosed Central Nervous System Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 19
- 试验地点
- 1
- 主要终点
- Complete Remission Rate (CRR)
研究概览
简要总结
Subjects who met the inclusion/exclusion criteria were included in the experimental group after signing the informed consent form. One course of Z(R)-MTX(TMZ) treatment was given. After the results of the second-generation sequencing were reported, selinisol was added to the original treatment plan for those with TP53 mutations, and the original treatment plan was continued for those without TP53 mutations. Each course of treatment lasts for three weeks. A mid-term assessment is conducted after three courses of treatment, and a final assessment is carried out after six courses of treatment. After the mid-term or final assessment:
If the PR is not achieved or the disease progresses at any time, the subjects are withdrawn from the group and receive salvage treatment.
If the subjects achieve CR or PR, they enter maintenance treatment and continue with zanubrutinib for 2 years. For young patients (< 65 years old), they can choose whether to receive ASCT as consolidation treatment according to their personal will, and then follow up and observe until 3 years have passed.
SD/PD patients receive subsequent treatment after being judged by the researchers
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have a full understanding of this study and voluntarily sign the informed consent form.
- •Untreated patients with primary central nervous system lymphoma (PCNSL) confirmed by pathology (immunotyping) according to the 2016 WHO classification of lymphoid neoplasms.
- •Diffuse large B-cell lymphoma (DLBCL) originating from the central nervous system (CNS) without involvement of other organs, confirmed by PET-CT or contrast-enhanced CT.
- •Expected survival greater than 3 months.
- •Laboratory test results meeting all of the following:
- •Creatinine clearance rate ≥ 50 mL/min (calculated by the Cockcroft-Gault formula).
- •International normalized ratio (INR) ≤ 1.5 × ULN or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN. Patients on warfarin may have INR 2-
- •Left ventricular ejection fraction (LVEF) ≥ 50%.
- •Glomerular filtration rate (GFR) ≥ 60 mL/min.
- •Male or female patients of childbearing potential must agree to use effective contraception (e.g., double-barrier methods, condoms, oral or injectable contraceptives, intrauterine device) during the study and for 30 days after the last dose.
- •Postmenopausal women (> 45 years old and amenorrheic > 1 year) or surgically sterilized women are exempt from this requirement.
排除标准
- •Contraindication to any drug included in the treatment regimen.
- •History of clinically significant liver disease, including viral or other hepatitis or cirrhosis.
- •Hepatitis B: Positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with HBV-DNA above ULN.
- •Active hepatitis C: Positive HCV antibody with detectable HCV-RNA.
- •Human Immunodeficiency Virus (HIV) infection.
- •Congestive heart failure (New York Heart Association Class > II) or history within 6 months of acute myocardial infarction, unstable angina, stroke, or transient ischemic attack.
- •Hereditary long QT syndrome or QTc > 480 ms (QTc calculated using Fridericia's formula, QTcF = QT / RR^0.33).
- •Other malignancies within 5 years, except: completely cured cervical carcinoma in situ, basal cell carcinoma of the skin, breast carcinoma in situ, or another primary cancer that has been cured and not recurred within 5 years.
- •Pregnant or lactating women, or women planning pregnancy during the study period.
- •History of significant neurological or psychiatric disorders, including substance or psychotropic-drug abuse.
- •Clinically significant active infection.
- •Inability to take or swallow oral medication, or conditions affecting drug absorption (e.g., chronic diarrhea, intestinal obstruction).
研究组 & 干预措施
Single Arm: Zanubrutinib + Rituximab + MTX ± Selinexor
This single treatment arm includes an induction phase of six 21-day cycles where participants receive:
Zanubrutinib 160 mg orally twice daily, Rituximab 375 mg/m² intravenously on Day 0, MTX 3.5 mg/m² intravenously on Days 1.
Before starting the second cycle, TP53 mutation status will be assessed. Participants positive for TP53 mutation will have Selinexor 60 mg orally added on Days 1 and 3 weekly.
Following induction, a maintenance phase consists of Zanubrutinib 160 mg orally twice daily for up to 2 years or until disease progression or unacceptable toxicity.
This study uses a biomarker-driven approach within a single-arm design without randomization or comparator arms.
干预措施: Zanubrutinib + Rituximab + MTX ± Selinexor (Drug)
结局指标
主要结局
Complete Remission Rate (CRR)
时间窗: At the end of Cycle 6 and at 4 weeks after completion of Cycle 6 (each cycle is 21 days).
Complete Remission Rate (CRR) is defined as the proportion of participants achieving complete remission based on predefined hematologic and/or imaging criteria at the end of treatment Cycle 6.
次要结局
- Overall Survival (OS)(From initiation of study treatment to death from any cause or last follow-up, whichever occurs first, up to 2 years.)