Phase I/II Study of Oral Clofarabine + Rituximab in Relapsed B Cell NHL
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 1
- 主要终点
- The Maximum Tolerated Dose (MTD) of Oral Clofarabine in Adult Patients With Relapsed CD20+ Non-Hodgkin Lymphoma(NHL)
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy, such as clofarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving clofarabine together with rituximab may kill more cancer cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of clofarabine when given together with rituximab and to see how well they work in treating patients with relapsed B-cell non-Hodgkin lymphoma.
详细描述
OBJECTIVES:
Primary
- To determine the maximum tolerated dose of clofarabine in adult patients with relapsed CD20-positive B-cell non-Hodgkin lymphoma (NHL).
- To estimate objective response rates of clofarabine in combination with rituximab in these patients.
Secondary
- To determine the 1-year progression-free survival of this regimen using the mean tolerated dose in these patients.
- To determine the safety and efficacy of this regimen in these patients.
- To determine if clofarabine acts as an inhibitor of DNA methylation similar to cladribine by performing scientific correlates.
- To determine whether response to clofarabine alone or in combination with rituximab correlates with changes in global serum DNA methylation index.
- To identify the gene activated by clofarabine therapy by using genomic DNA and RNA array technology.
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 89 Years（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
Oral Clofarabine + Rituximab in Relapsed B Cell NHL
Phase I: Oral Clofarabine x 14 days for up to 8 cycles at assigned dose level below (1 cycle equals 14 days on drug, 14 days off).
Rituximab weekly for 4 weeks than monthly for up to 8 cycles on day 1 of cycle 375 mg/m2 IV
Dose Level 1: 2 mg Dose Level 2: 4 mg Dose Level 3: 6 mg
Phase II:
Oral Clofarabine x 14 days for up to 8 cycles (Dose determined from phase I) AND Rituximab weekly for 4 weeks than monthly for up to 8 cycles on day 1 of cycle 375 mg/m2 IV
干预措施: rituximab (Biological)
Oral Clofarabine + Rituximab in Relapsed B Cell NHL
Phase I: Oral Clofarabine x 14 days for up to 8 cycles at assigned dose level below (1 cycle equals 14 days on drug, 14 days off).
Rituximab weekly for 4 weeks than monthly for up to 8 cycles on day 1 of cycle 375 mg/m2 IV
Dose Level 1: 2 mg Dose Level 2: 4 mg Dose Level 3: 6 mg
Phase II:
Oral Clofarabine x 14 days for up to 8 cycles (Dose determined from phase I) AND Rituximab weekly for 4 weeks than monthly for up to 8 cycles on day 1 of cycle 375 mg/m2 IV
干预措施: clofarabine (Drug)
Oral Clofarabine + Rituximab in Relapsed B Cell NHL
Phase I: Oral Clofarabine x 14 days for up to 8 cycles at assigned dose level below (1 cycle equals 14 days on drug, 14 days off).
Rituximab weekly for 4 weeks than monthly for up to 8 cycles on day 1 of cycle 375 mg/m2 IV
Dose Level 1: 2 mg Dose Level 2: 4 mg Dose Level 3: 6 mg
Phase II:
Oral Clofarabine x 14 days for up to 8 cycles (Dose determined from phase I) AND Rituximab weekly for 4 weeks than monthly for up to 8 cycles on day 1 of cycle 375 mg/m2 IV
干预措施: DNA methylation analysis (Genetic)
Oral Clofarabine + Rituximab in Relapsed B Cell NHL
Phase I: Oral Clofarabine x 14 days for up to 8 cycles at assigned dose level below (1 cycle equals 14 days on drug, 14 days off).
Rituximab weekly for 4 weeks than monthly for up to 8 cycles on day 1 of cycle 375 mg/m2 IV
Dose Level 1: 2 mg Dose Level 2: 4 mg Dose Level 3: 6 mg
Phase II:
Oral Clofarabine x 14 days for up to 8 cycles (Dose determined from phase I) AND Rituximab weekly for 4 weeks than monthly for up to 8 cycles on day 1 of cycle 375 mg/m2 IV
干预措施: gene expression analysis (Genetic)
Oral Clofarabine + Rituximab in Relapsed B Cell NHL
Phase I: Oral Clofarabine x 14 days for up to 8 cycles at assigned dose level below (1 cycle equals 14 days on drug, 14 days off).
Rituximab weekly for 4 weeks than monthly for up to 8 cycles on day 1 of cycle 375 mg/m2 IV
Dose Level 1: 2 mg Dose Level 2: 4 mg Dose Level 3: 6 mg
Phase II:
Oral Clofarabine x 14 days for up to 8 cycles (Dose determined from phase I) AND Rituximab weekly for 4 weeks than monthly for up to 8 cycles on day 1 of cycle 375 mg/m2 IV
干预措施: microarray analysis (Genetic)
Oral Clofarabine + Rituximab in Relapsed B Cell NHL
Phase I: Oral Clofarabine x 14 days for up to 8 cycles at assigned dose level below (1 cycle equals 14 days on drug, 14 days off).
Rituximab weekly for 4 weeks than monthly for up to 8 cycles on day 1 of cycle 375 mg/m2 IV
Dose Level 1: 2 mg Dose Level 2: 4 mg Dose Level 3: 6 mg
Phase II:
Oral Clofarabine x 14 days for up to 8 cycles (Dose determined from phase I) AND Rituximab weekly for 4 weeks than monthly for up to 8 cycles on day 1 of cycle 375 mg/m2 IV
干预措施: polymerase chain reaction (Genetic)
Oral Clofarabine + Rituximab in Relapsed B Cell NHL
Phase I: Oral Clofarabine x 14 days for up to 8 cycles at assigned dose level below (1 cycle equals 14 days on drug, 14 days off).
Rituximab weekly for 4 weeks than monthly for up to 8 cycles on day 1 of cycle 375 mg/m2 IV
Dose Level 1: 2 mg Dose Level 2: 4 mg Dose Level 3: 6 mg
Phase II:
Oral Clofarabine x 14 days for up to 8 cycles (Dose determined from phase I) AND Rituximab weekly for 4 weeks than monthly for up to 8 cycles on day 1 of cycle 375 mg/m2 IV
干预措施: high performance liquid chromatography (Other)
Oral Clofarabine + Rituximab in Relapsed B Cell NHL
Phase I: Oral Clofarabine x 14 days for up to 8 cycles at assigned dose level below (1 cycle equals 14 days on drug, 14 days off).
Rituximab weekly for 4 weeks than monthly for up to 8 cycles on day 1 of cycle 375 mg/m2 IV
Dose Level 1: 2 mg Dose Level 2: 4 mg Dose Level 3: 6 mg
Phase II:
Oral Clofarabine x 14 days for up to 8 cycles (Dose determined from phase I) AND Rituximab weekly for 4 weeks than monthly for up to 8 cycles on day 1 of cycle 375 mg/m2 IV
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
The Maximum Tolerated Dose (MTD) of Oral Clofarabine in Adult Patients With Relapsed CD20+ Non-Hodgkin Lymphoma(NHL)
时间窗: 14 days for up to 8 cycles (1 cycle equals 14 days on drug, 14 days off drug) for a total of up to 224 days
Initially, 3 patients will be enrolled into a dose level during the dose-escalation portion: * If no patient experiences dose-limiting toxicities during the first 4 weeks, then 3 patients will be enrolled into the next dose level. * If one of the three patients develops dose-limiting toxicities, then 3 additional patients will be enrolled in that cohort. If none of the additional 3 patients experiences dose-limiting toxicities, then further dose-escalation occurs. * If one additional patient experiences dose-limiting toxicities, then the maximum tolerated dose is exceeded.
Estimate Objective Response Rates of Oral Clofarabine in Combination With Rituximab in Relapsed CD20+NHL
时间窗: Oral Clofarabine x 14 days for up to 8 cycles (1 cycle equals 14 days on drug, 14 days off drug) for a total of up to 224 days AND Rituximab weekly for 4 weeks than monthly for up to 8 cycles on day 1 of cycle
次要结局
- Determine One-year Progression Free Survival Using the MTD of Clofarabine With Rituximab in Relapsed CD20+NHL(One year after study drug(s) have been given. Duration of study up to 1 year.)
- Whether Clofarabine Acts as an Inhibitor of DNA Methylation Similar to Cladribine by Performing Scientific Correlates(Duration of the study, up to 1 year.)
- Determine the Safety and Efficacy of Clofarabine in Combination With Rituximab(Duration of the study, up to 1 year.)
- Whether Response to Clofarabine Alone or in Combination With Rituximab Correlates With Changes in Global Serum DNA Methylation Index(Duration of the study, up to 1 year.)
- Identity of the Gene Activated by Clofarabine Therapy by Using Genomic DNA and RNA Array Technology(Twice monthly at standard of care visits for 3 months post last cycle of chemotherapy.)