Plasma and Cerebrospinal Fluid (CSF) Pharmacokinetics of Bendamustine as a Component of Salvage Therapy for Primary Central Nervous System Lymphoma (PCNSL)
试验速览
- 阶段
- 2 期
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Overall response rate (ORR)
研究概览
简要总结
This pilot study will i) evaluate the efficacy and the safety of bendamustine-based combination chemotherapy and ii) investigate the pharmacokinetics (PK)of bendamustine in plasma and CSF when given as salvage treatment for patients with relapsed or refractory primary central nervous system lymphoma (PCNSL).
详细描述
A relatively high proportion of patients diagnosed with primary CNS lymphoma will experience recurrent disease, yet therapy options are limited in salvage therapy. Based on the demonstrated activity and proposed additive mechanisms of the chemotherapeutic agents included in the bendamustine-based combination regimen, the efficacy and safety of R-B(O)AD will be evaluated for treatment of relapsed/refractory (R/R) primary CNS lymphoma. Evidence from previous preclinical tissue distribution studies and single agent intravenous drug therapy trials in CNS malignancies suggests that bendamustine penetrates brain and tumor tissue, however there are no clinical data available on the PK of bendamustine in the CSF. This study will evaluate the PK of plasma and CSF drug levels through a population based nonlinear mixed-effects model approach in a R/R PCNSL cohort with the goals to define the currently unknown PK profile of bendamustine in the CSF and to further characterize the relationship between plasma and CSF drug levels, and the influence of exposure on response to therapy.
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
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •PCNSL of diffuse large B-cell lymphoma (DLBCL) with a CNS lesion by tissue biopsy
- •Age ≥ 19 years old
- •Relapsed or refractory PCNSL after frontline combined chemotherapy or radiation
- •ECOG performance status 0-2
- •Absolute neutrophil count ≥ 1000/uL
- •Platelets ≥ 100,000/uL
- •Total bilirubin ≤ 1.5 x ULN (upper limit of normal)
- •Aspartate aminotransferase (AST) ≤ 3 x ULN
- •Creatinine ≤ 2.0 x ULN
排除标准
- •PCNSL of other than DLBCL or T-cell lymphoma with a CNS lesion by tissue biopsy
- •Any of the following: pregnant women, nursing women, men or women of childbearing potential who are unwilling to employ adequate contraception
- •Uncontrolled infection
- •Therapy with myelosuppressive chemotherapy or biologic therapy < 21 days prior to registration
- •Persistent toxicities ≥ grade 3 from prior chemotherapy or biologic therapy regardless of interval since last treatment
- •History of thromboembolic episodes ≤ 3 months prior to registration
- •Active hepatitis B or C with uncontrolled disease
- •Active other malignancy requiring treatment that would interfere with the assessments of response of the lymphoma to protocol treatment
- •Any severe and/or uncontrolled medical conditions or other conditions that could adversely impact their ability to participate in the study
- •Major surgery ≤ 4 weeks prior to registration or have not recovered from side effects of such therapy
研究组 & 干预措施
R-B(O)AD
Intravenous R-B(O)AD every 4 weeks for up to 4 cycles
干预措施: R-B(O)AD (Drug)
结局指标
主要结局
Overall response rate (ORR)
时间窗: 2 year
rate of complete or partial response (CR/PR)
次要结局
- Toxicity based on NCI Common Terminology Criteria version 4.0(2 year)
- Progression-free survival (PFS)(2 years)
- Overall survival (OS)(2 years)
- Maximum concentration [Cmax] of bendamustine in plasma and CSF(6 months)
- Area under the curve [AUC] of bendamustine in plasma and CSF(6 months)
研究者
Deok-Hwan Yang
Principal Investigator
Chonnam National University Hospital