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
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- 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
研究概览
简要总结
This phase I trial is studying the side effects and best dose of flavopiridol in treating patients with B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma. Drugs used in chemotherapy, such as alvocidib, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.
详细描述
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.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- 未提供
研究组 & 干预措施
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.
干预措施: alvocidib (Drug)
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.
干预措施: pharmacological study (Other)
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.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
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
时间窗: Day 1, every 2 courses, at 2 months and then every 3 months for 5 years after completion of study treatment
Assessed utilizing the NCI Common Terminology Criteria for Adverse Events version 3.0.
Dose-limiting toxicity of alvocidib as consolidation chemotherapy after cytoreduction chemotherapy in patients with B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma
时间窗: Course 1
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.
次要结局
- Pharmacokinetics and cellular pharmacodynamics of alvocidib administered in this schedule(Baseline and day 1)
- Complete response (CR) and overall response rate (CR and partial response) of alvocidib in patients with previously-treated CLL(Baseline, every 2 courses, at 2 months and then every 3 months for 5 years after completion of study treatment)