Phase I Study of UCN-01 and Cytarabine (ARA-C) in Patients With Acute Myelogenous Leukemia, and Myelodysplastic Syndromes
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 2
- 主要终点
- Maximum Tolerated Dose (MTD) Cytarabine + UCN-01
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. UCN-01 may make cancer cells more sensitive to cytarabine.
PURPOSE: Phase I trial to study the effectiveness of cytarabine and UCN-01 in treating patients who have refractory or relapsed acute myelogenous leukemia or myelodysplastic syndrome.
详细描述
OBJECTIVES: I. Determine the maximum tolerated dose of cytarabine when combined with UCN-01 in patients with refractory or relapsed acute myelogenous leukemia or myelodysplastic syndrome. II. Determine the dose limiting toxicity, pharmacokinetics, and pharmacodynamics of this regimen in these patients. III. Assess the antileukemia effect of this regimen in this patient population.
OUTLINE: This is a dose escalation, multicenter study of cytarabine. Patients receive cytarabine IV over 24 hours on days 1-4 of each course. Patients receive UCN-01 IV over 24 hours on days 2-4 of course 1 and over 36 hours beginning on day 2 of subsequent courses. Treatment repeats every 4 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of cytarabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 6 patients experience dose limiting toxicity.
PROJECTED ACCRUAL: A maximum of 30 patients will be accrued for this study.
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
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with refractory or relapsed acute myelogenous leukemia, or myelodysplastic syndromes (RAEB or RAEB-T).
- •Performance status of =< 2
- •Signed informed consent indicating that patients are aware of the investigational nature of this study in keeping with the policies of the hospital. The only acceptable consent form is the one attached at the end of this protocol for each participating institution.
- •Patients must have been off chemotherapy for 2 weeks prior to entering this study and recovered from the toxic effects of that therapy, unless there is evidence of rapidly progressive disease.
- •Bilirubin and creatinine (or creatinine clearance) should be within institutional normal limits.
- •Patients must have relapsed or failed to respond after high-dose ara-C-based (>=1g/m2/day x 3 days) chemotherapy.
- •Corrected DLCO >50%.
- •Patients with >=3 cardiac risk factors (smoking, hypertension, family history of coronary artery disease, diabetes mellitus, hypercholesterolemia) should have a nuclear medicine stress test.
排除标准
- •The anti-proliferative activity of the experimental drug may be harmful to the developing fetus or nursing infant. Therefore, pregnant and nursing females will be excluded. Patients of childbearing potential should practice effective methods of contraception.
- •Patients who are eligible for allogeneic marrow transplant and who have a donor will be offered transplant.
- •Patients with existing pulmonary diseases, history of coronary artery disease or who have received radiotherapy to the mediastinum.
研究组 & 干预措施
Cytarabine + UCN-01
干预措施: 7-hydroxystaurosporine (UCN-01) (Drug)
Cytarabine + UCN-01
干预措施: Cytarabine (Ara-C) (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) Cytarabine + UCN-01
时间窗: 4 week cycle
次要结局
未报告次要终点