Zanubrutinib Monotherapy in Relapsed/Refractory Central Nervous System Lymphoma
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Overall response rate (ORR)
研究概览
简要总结
Zanubrutinib is a novel BTK inhibitor with proven activity in patients with various B-cell lymphomas addicted to the B-cell receptor signaling pathway.
详细描述
Studies involving gene expression profiling and next generation sequencing have demonstrated that CNS lymphomas mostly are of the ABC-subtype and harbor mutations that reinforce BCR signaling. Ibrutinib, as the first BTK inhibitor, showed substantial activity in patients with R/R PCNSL and R/R SCNSL. Zanubrutinib is a novel BTK inhibitor with proven activity in patients with various B-cell lymphomas addicted to the B-cell receptor signaling pathway. In addition, pharmacological studies demonstrated the free drug exposure of zanubrutinib at 160 mg BID is roughly 10 times that of ibrutinib at 560 mg QD, and penetration into the CNS by zanubrutinib and ibrutinib is similar, suggesting the potential activity of zanubrutinib in the treatment of CNS lymphomas. However, the outcome of R/R PCNSL and R/R SCNSL patients treated with zanubrutinib monotherapy is still unclear.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Key inclusion criteria:
- •Able to understand and willing to sign a written informed consent document
- •Men and woman at least 18 years of age on the day of consenting to the study
- •Histologically documented DLBCL.
- •Relapsed/refractory PCNSL or relapsed/refractory SCNSL
- •Patients with parenchymal lesions must have unequivocal evidence of disease progression on imaging (MRI or the brain or head CT) prior to study enrollment. For patients with leptomeningeal disease only, CSF cytology must document lymphoma cells and/or imaging findings consistent with CSF disease prior to study enrollment.
- •An ECOG performance status≤2
- •Adequate bone marrow and organ function shown by:
- •(1) Neutrophils ≥ 0.75 x 109/L independent of growth factor support within 7 days of study entry (2) Platelets ≥ 50 x 109/L independent of growth factor support or transfusion within 7 days of study entry (3) Creatinine clearance of ≥ 30 mL/min (4) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x upper limit of normal (ULN) (5) Bilirubin ≤ 1.5 x ULN (6) International normalized ratio ≤ 1.5 and activated partial thromboplastin time ≤ 1.5 x ULN.
- •Recovered to grade 1 toxicity from prior therapy before the first dose of study drug
- •Agree to use highly effective methods of birth control during the period of therapy and for 3 months after the last dose of the study drug.
排除标准
- •Patients with SCNSL actively receiving treatment for extra-CNS disease
- •Concurrently using other approved or investigational antineoplastic agents
- •Prior chemotherapy, targeted therapy, or radiation therapy within 4 weeks
- •Prior exposure to a BTK inhibitor
- •Concurrently using more than 8mg of dexamethasone daily or the equivalent
- •History of other active malignancies within 2 years of study entry
- •Major surgery within 4 weeks of screening or not recovered from the side effects of such surgery
- •Known to have human immunodeficiency virus (HIV) infection
- •Known to have a history of active or chronic infection with hepatitis C virus (HCV) or hepatitis B virus (HBV) as determined by serologic tests
- •Active infection systemic including infections requiring oral or intravenous antimicrobials
- •Currently active clinically significant cardiovascular disease
- •QTcF > 480 msecs or other significant electrocardiogram (ECG) abnormalities
- •Unable to swallow capsules or disease significantly affecting gastrointestinal function
- •Any life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could have compromised the patient's safety, or put the study at risk
- •Required ongoing treatment with medication that are strong cytochrome P450, family 3, subfamily A (CYP3A) inhibitors or strong CYP3A inducers
- •History of stroke or intracranial hemorrhage within 6 months prior to enrollment
- •Inability to comply with study procedures
- •Pregnant or lactating women
- •Prior allogenic hematopoietic stem cell transplantation (autologous stem cell transplant is NOT an exclusion)
研究组 & 干预措施
Zanubrtuinib
Zanubrutinib 320mg Qd
干预措施: Zanubrutinib (Drug)
结局指标
主要结局
Overall response rate (ORR)
时间窗: 2 years
Based on the Investigator assessed CR and PR, with the enhanced CT scan, the cerebrospinal fluid (CSF) examination, and the ophthalmological examination.
次要结局
- Progression-free survival (PFS)(2 years)
- Treatment-related adverse events (TRAE)(During zanubrutinib treatment until 30+/-7 days after discontinuation.)
- Time to response (TTR)(2 years)
- Duration of response (DOR)(2 years)
- The concentration of zanunbrutinib in CSF and plasma(2 months)
研究者
Xiao-Jun Huang
Associate Chief of Hematology
Peking University People's Hospital