The Efficacy and Safety of Zanuburutinib in Relapsed and Refractory Idiopathic Multicentric Castleman Disease (iMCD): a Prospective, Single-center, Single-arm Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Overall response rate (ORR) at Week 24
研究概览
简要总结
To explore the effectiveness and safety of Zanuburutinib in relapsed and refractory idiopathic Multicentric Castleman's disease (iMCD) patients.
详细描述
This is a single center, open-labeled , single arm, prospective study which includes a safety run-in phase. The primary endpoint is the overall response rate which includes complete response (CR) and partial response (PR) at Week 12 and Week 24. The secondary endpoints include progression-free survival (PFS), overall survival (OS), and adverse events. There are two phases of the study. The first phase is the 'safety run-in phase'which plans to enroll 6 patients who would be observed for safety issues for 12 weeks after study drug administration. If no Grade ≥ 4 (CTCAE) adverse events (AE) occurs during this phase, the study would enter the second phase; if Grade ≥ 4 (CTCAE) AE happens during this phase, the study would be terminated. In the second phase of the study, another 24 patients would be enrolled. All enrolled patients would receive the study drug until progression of disease, intolerability of the drugs or Week 96 and would be followed every 4 weeks in the first 12 weeks, every 12 weeks until Week 48 and every 24 weeks until Week 96. The follow-up phase to assess PFS and OS will last from initiation of study drug to 36 months after enrollment (evaluation would be carried out every 24 weeks after Week 96). The total study duration will be 4 years after the last patient starts study medication.
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
盲法说明
This will be an open label study.
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
- •fulfilled the CDCN (Castleman Disease Collaborative Network) diagnostic criteria of iMCD
- •relapsed or refractory disease. Relapsed = patients who ever achieved overall partial response (PR) or complete response (CR) with prior lines of therapy suffered from progressive disease (PD); refractory = iMCD patients who never achieved PR or CR with the first-line treatment but suffered from PD during treatment.
- •Eastern Cooperative Oncology Group performance status (ECOG-PS ≤ 2)
- •Neutrophil count ≥ 0.75×10^9/L, hemoglobin ≥ 70 g/L and platelet count > 30×10^9/L
- •Total bilirubin ≤ 2 x ULN (upper limit of normal), AST（aspartate aminotransferase） or ALT（Alanine aminotransferase）≤ 2.5 x ULN
- •INR （international normalized ratio) and APTT(activated partial thromboplastin time) ≤ 1.5 x ULN；eGFR>25ml/min/1.73m2
- •estimated survival ≥ 3 months
- •agree to take birth control methods during study period for women of reproductive age
- •agree to provide informed consent
排除标准
- •concurrent malignancies
- •prior history of receiving any kind of BTK (Bruton's tyrosine kinase) inhibitors
- •patients with SLE (systemic lupus erythematosus), HHV-8 (human herpesvirus-8) infection or POEMS syndrome
- •History of major surgery or radiation therapy within 4 weeks before initiation of study drug
- •history of myocardial infarction within 1 years
- •patient with history of heart failure (NYHA 3 or 4) would be excluded unless his LVEF(left ventricular ejection fraction) ≥ 50% within 1 months
- •primary cardiomyopathy; Qtc > 450ms for men and > 470ms for women
- •breast feeding or pregnant women
- •intolerance for oral regimen due to gastro-intestinal disorders
- •uncontrolled infection
- •positive HBV(hepatitis B virus)-DNA titers or positive HbsAg; positive HCV(hepatitis C virus)antibody; patients with HIV infection
- •patients with history of bleeding disorders
- •cerebral infarction or intracranial bleeding within 6 months
- •active bleeding disorders within 2 months
- •taking anti-platelet or anticoagulation drugs
- •taking drugs which strongly inhibit P450 CYP3A
- •patients or their relatives fail to understand the purpose of the study
- •any other conditions that the investigators consider to be not appropriate for inclusion
研究组 & 干预措施
Zanuburutinib
Oral Zanuburutinib 160mg twice a day
干预措施: Zanubrutinib (Drug)
结局指标
主要结局
Overall response rate (ORR) at Week 24
时间窗: From date of treatment initiation to 24 weeks after treatment
Overall response (including partial response and complete response) rate at week 24 after zanuburutinib therapy
Overall response rate (ORR) at Week 12
时间窗: From date of treatment initiation to 12 weeks after treatment
Overall response (including partial response and complete response) rate at week 12 after zanuburutinib therapy
次要结局
- Overall survival(From date of treatment initiation until the date of death from any cause, whichever came first, assessed up to 36 months)
- Progression free survival(From date of treatment initiation until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months)
- Number of Participants With Treatment-related Adverse Events(From initiation study regimen to 3 months after the end of treatment or to time point of the initiation of second line therapy)