An Open-label Phase II Study to Investigate the Efficacy, Safety, and Pharmacokinetics of Tirabrutinib in Patients With Primary Central Nervous System Lymphoma (PCNSL)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 119
- 试验地点
- 39
- 主要终点
- Overall response rate (ORR) (Part A)
研究概览
简要总结
This study will evaluate the efficacy, safety, and pharmacokinetics of tirabrutinib monotherapy in patients with relapsed or refractory PCNSL (Part A), and tirabrutinib in combination with one of two different high dose methotrexate based regimens (methotrexate/ temozolomide/rituximab or rituximab/methotrexate/procarbazine/ vincristine) as first line therapy in patients with newly diagnosed, treatment naïve PCNSL (Part B)
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Tirabrutinib monotherapy in patients with relapsed or refractory PCNSL (Part A)
Patients with relapsed or refractory PCNSL who meet eligibility criteria will be enrolled to receive tirabrutinib monotherapy.
干预措施: Tirabrutinib (Drug)
Tirabrutinib + MTR in patients with newly diagnosed, treatment naïve PCNSL (Part B, Arm 1)
Patients with newly diagnosed treatment naïve PCNSL who meet eligibility criteria will be enrolled to receive tirabrutinib + methotrexate/temozolomide/rituximab (MTR)
干预措施: Tirabrutinib (Drug)
Tirabrutinib + R-MPV in patients with newly diagnosed, treatment naïve PCNSL (Part B, Arm 2)
Patients with newly diagnosed treatment naïve PCNSL who meet eligibility criteria will be enrolled to receive tirabrutinib + rituximab/methotrexate/procarbazine/vincristine (R-MPV)
干预措施: Tirabrutinib (Drug)
结局指标
主要结局
Overall response rate (ORR) (Part A)
时间窗: 1 year
Overall response rate is defined as the proportion of patients with a best overall response of Complete response (CR), Complete response - unconfirmed (CRu), or (=partial response (PR) as determined by an independent review committee according to the International PCNSL Collaborative Group (IPCG) criteria.
Tirabrutinib dose estimate (Part B)
时间窗: 1 month
Estimate of tirabrutinib dose in combination with each backbone induction regimen (MTR and R-MPV) based upon treatment related AEs, SAEs, and toxicities observed during the initial cycle of induction therapy in the dose-ranging phase
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) during induction (Part B)
时间窗: 4 months
Adverse events at each visit with the NCI CTCAE v5.0 used as a guide for the grading of severity.
Complete response rate (CRR) (Part B)
时间窗: 4 months
Complete response rate is defined as the proportion of patients with a best overall response of CR or CRu as determined by an independent review committee according to the IPCG criteria.
次要结局
- Time to response (TTR) (Part A and B)(1 year)
- PK parameters (Tmax) of tirabrutinib in the plasma (Part A and B)(29 days)
- Best overall response (BOR) (Part A and B)(1 year)
- Change in corticosteroid dose (Part A)(2 years)
- PK parameters (AUC) of tirabrutinib in the plasma (Part A and B)(29 days)
- Duration of response (DOR) (Part A and B)(2 years)
- Incidence and severity of AEs and SAEs (Part A and B)(2 years)
- Laboratory abnormality profile of tirabrutinib as measured by incidence and severity of clinical laboratory abnormalities (Part A and B)(2 years)
- PK parameters (Cmax) of tirabrutinib in the plasma (Part A and B)(29 days)
- ECG parameters by 12 lead ECG (Part A and B)(2 years)