Alvocidib in Treating Patients With B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
A Phase I Dose-Escalation Study of Flavopiridol (NSC 649890) Administered as a 30 Minute Loading Dose Followed by a 4-Hour Infusion in Patients With B-Cell Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) Following Cytoreduction With Chemotherapy
研究概览
地位
条件
详细说明
PRIMARY OBJECTIVES:
I. Determine the toxicity profile, dose-limiting toxicity, and maximum tolerated dose of flavopiridol (alvocidib) as consolidation chemotherapy after cytoreduction chemotherapy in patients with B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma.
SECONDARY OBJECTIVES:
I. Determine the pharmacokinetics and cellular pharmacodynamics of flavopiridol in these patients.
II. Determine the complete response (CR) and overall response rate (CR and partial response) of patients treated with flavopiridol.
OUTLINE: This is a dose-escalation study. Patients receive alvocidib intravenously (IV) over 30 minutes (loading dose), followed by alvocidib IV over 4 hours on days 1, 8, and 15.
Treatment repeats every 5 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. A total of 12 patients are treated at the MTD (i.e., recommended phase II dose). Patients undergo blood collection at baseline and periodically during study for pharmacokinetic and cytokine studies (levels of tumor necrosis factor-alpha, interleukin [IL]-6, -11, and -16) by enzyme-linked immunosorbent assay (ELISA). Interphase cytogenetics, p53 mutational status, p53/ATM function, V_H mutational status, zeta-chain-associated protein kinase 70 (ZAP-70) overexpression, and single nucleotide polymorphisms are also examined.
After completion of study treatment, patients are followed at 2 months and then every 3 months for 5 years.
研究类型
注册 (实际的)
阶段
- 阶段1
联系人和位置
学习地点
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Ohio
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Columbus、Ohio、美国、43210
- Ohio State University Medical Center
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
Diagnosis of 1 of the following:
- B-cell chronic lymphocytic leukemia (CLL)
- Small lymphocytic lymphoma (SLL)
Must have received 1-3 prior therapies for CLL
- Completed therapy 2-12 months ago
- Prior therapy must have led to a partial response or greater
- No evidence of progressive disease
- ECOG performance status 0-2
- Absolute neutrophil count ≥ 1,000/mm³
- WBC ≤ 5,000/mm³
- Platelet count ≥ 50,000/mm³
- Cytopenia allowed
- Creatinine < 2.0 mg/dL
- Bilirubin ≤ 1.5 times normal (unless due to Gilbert's disease or hemolysis)
- AST ≤ 2 times normal (unless due to hemolysis)
- No secondary malignancy or other disease that would limit survival to < 2 years
- No history of inflammatory bowel disease unless inactive for > 2 years
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- See Disease Characteristics
- No other concurrent chemotherapy
- No concurrent radiotherapy
- No concurrent dexamethasone or other corticosteroid-based antiemetics
- No concurrent chronic corticosteroid therapy
No other concurrent hormonal therapy except for the following:
- Steroids for new adrenal failure
- Hormones for nondisease-related conditions (e.g., insulin for diabetes)
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:不适用
- 介入模型:单组作业
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的:Treatment (chemotherapy)
Patients receive alvocidib IV over 30 minutes (loading dose), followed by alvocidib IV over 4 hours on days 1, 8, and 15.
Treatment repeats every 5 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.
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相关研究
鉴于IV
其他名称:
相关研究
其他名称:
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Toxicity profile of alvocidib administered as a 30 minute loading dose followed by a 4-hour infusion once weekly for 3 consecutive weeks every 5 weeks as consolidation therapy following cytoreduction chemotherapy
大体时间:Day 1, every 2 courses, at 2 months and then every 3 months for 5 years after completion of study treatment
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Assessed utilizing the NCI Common Terminology Criteria for Adverse Events version 3.0.
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Day 1, every 2 courses, at 2 months and then every 3 months for 5 years after completion of study treatment
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Dose-limiting toxicity of alvocidib as consolidation chemotherapy after cytoreduction chemotherapy in patients with B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma
大体时间:Course 1
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The National Cancer Institute Common Toxicity Criteria version 3.0 will be used to characterize toxicity.
If no patients experience dose-limiting toxicity, dose escalation will occur.
If 1 patient has a dose limiting toxicity, 3 additional patients will be enrolled at that dose.
If fewer than 2 of 6 patients experiences dose limiting toxicity, then the next highest dose level will be used for the subsequent cohort of 3 patients.
If at any dose level two or more of the six patients experience a dose limiting toxicity, 3 additional patients will be treated at the previous dose level.
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Course 1
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
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Pharmacokinetics and cellular pharmacodynamics of alvocidib administered in this schedule
大体时间:Baseline and day 1
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Cytokine studies will be examined by standard ELISA assays to determine if increase IL-6 correlates with hypotension, hypoxemia, and tachycardia observed following treatment and to identify the source of production of this cytokine.
We will examine interphase cytogenetics, p53 mutational status, p53/ATM functional assay, VH mutational status, and ZAP-70 over-expression.
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Baseline and day 1
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Complete response (CR) and overall response rate (CR and partial response) of alvocidib in patients with previously-treated CLL
大体时间:Baseline, every 2 courses, at 2 months and then every 3 months for 5 years after completion of study treatment
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Criteria for response will utilize the Revised National Cancer Institute-sponsored Working Group Guidelines.
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Baseline, every 2 courses, at 2 months and then every 3 months for 5 years after completion of study treatment
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合作者和调查者
调查人员
- 首席研究员:Leslie Andritsos、Ohio State University
出版物和有用的链接
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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