High-dose HMG-CoA Inhibitor Simvastatin for Patients With Relapsed CLL: Pilot Trial and Pharmacokinetic-pharmacodynamic Studies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Evaluate the feasibility of investigators to recruit, retain & evaluate responses in a pilot study of participants with relapsed/refractory CLL treated with 7.5 mg/kg of simvastatin taken orally twice daily on days 1-7 of every 21 day cycles for 6 cycles
研究概览
简要总结
The primary aim of this trial is to generate a preliminary analysis of this novel therapeutic approach and laboratory studies for patients with recurrent or refractory CLL. Further, this pilot trial will demonstrate the feasibility of the translational science methods proposed for this new collaboration of investigators. The investigators hypothesize that patients with relapsed CLL are recruitable to this study, that the methods for measuring simvastatin concentration and target protein translation are feasible, and that the investigators can efficiently apply the laboratory research methods to patient blood samples before and after patients have taken the study medication.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- 未提供
排除标准
- •Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- •Patients may not be receiving any other investigational agents.
- •Patients with known brain or nervous system disease should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to simvastatin.
- •Patients receiving any medications or substances that are inhibitors or inducers of CYP3A4 are ineligible. Lists including medications and substances known or with the potential to interact with the CYP3A4 isoenzymes are provided in the appendix.
- •Patients may not take other anti-cholesterol treatments during this study. Patients who were previously taking anti-cholesterol treatment prior to study entry must be off the anti-cholesterol medications for 14 days before enrolling on this trial.
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, diarrhea, myopathy, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Pregnant women are excluded from this study because HMG-CoA reductase inhibitors are a drug class with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with simvastatin, breastfeeding should be discontinued if the mother is treated with simvastatin.
- •HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with simvastatin.
研究组 & 干预措施
1
干预措施: Simvastatin (Drug)
结局指标
主要结局
Evaluate the feasibility of investigators to recruit, retain & evaluate responses in a pilot study of participants with relapsed/refractory CLL treated with 7.5 mg/kg of simvastatin taken orally twice daily on days 1-7 of every 21 day cycles for 6 cycles
时间窗: Begining of therapy and followed for 2 years after completing therapy
Evaluate the feasibility of the proposed methods to determine the plasma and intra-cellular pharmacokinetics after high-dose simvastatin
时间窗: During therapy
Evaluate the feasibility of proposed methods to determine if high-dose simvastatin treatment affects the prenylation dependent cellular localization of Rho GTPase proteins and to assess the apoptotic index of CLL cells from treated participants
时间窗: During therapy
Evaluate the feasibility of proposed methods to identify changes in gene expression following high-dose simvastatin treatment
时间窗: Druing treatment
次要结局
未报告次要终点
研究者
John Haslip
Director, Clinical Research and Data Management Shared Resource Facility
University of Kentucky