A Phase I Study of Depsipeptide in Selected Hematologic Malignancies (NSC 630176)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 试验地点
- 2
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.
PURPOSE: Phase I trial to study the effectiveness of FR901228 in treating patients who have hematologic cancer.
详细描述
OBJECTIVES:
- Determine the in vivo biologic effect of FR901228 (depsipeptide) in patients with chronic lymphocytic leukemia, small lymphocytic lymphoma, acute myeloid leukemia, or acute lymphoblastic leukemia.
- Determine the pharmacokinetics and cellular pharmacodynamics of this drug in these patients.
- Determine any preliminary anti-tumor activity of this drug in these patients.
OUTLINE: This is a dose-decreasing, multicenter study. Patients are stratified according to disease (chronic lymphocytic leukemia and small lymphocytic lymphoma vs acute myeloid leukemia and acute lymphoblastic leukemia).
Patients receive FR901228 (depsipeptide) IV over 4 hours on days 1, 8, and 15. Treatment repeats every 4 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.
Cohorts of 10 patients per stratum receive decreasing doses of FR901228 until the minimal active dose is determined. If 5 or more patients show clinical or biological response, the subsequent cohort is treated at a lower dose. If fewer than 5 patients respond, the subsequent cohort is treated at a higher dose.
研究设计
- 研究类型
- Interventional
- 主要目的
- Treatment
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
- •DISEASE CHARACTERISTICS:
- •Diagnosis of one of the following hematologic malignancies:
- •Chronic lymphocytic leukemia (CLL)
- •Small lymphocytic lymphoma (SLL) (including Waldenstrom's macroglobulinemia)
- •Acute myeloid leukemia (AML)
- •Acute lymphoblastic leukemia (ALL)
- •Stratum I (CLL and SLL):
- •Received at least one prior therapy containing a purine analog OR
- •Received another form of therapy (including alkylating agents) due to history of severe autoimmune disease, requirement for chronic corticosteroid, or other contraindication to purine analog therapy
- •Stratum II (AML and ALL):
- •Primary refractory or relapsed leukemia within the past year that is not amenable to curative therapy
- •Untreated or previously treated poor-risk leukemia defined by any of the following:
- •65 years of age and over
- •Poor-risk candidates for aggressive chemotherapy
- •Poor-risk cytogenetics (for AML, karyotype abnormalities other than t(8;21), inv(16), t(15;17))
- •PATIENT CHARACTERISTICS:
- •18 and over
- •Performance status:
- •Life expectancy:
- •At least 12 weeks
- •Hematopoietic:
- •Stratum I only:
- •No uncontrolled autoimmune hemolytic anemia
- •No idiopathic thrombocytopenic purpura
- •Stratum II only:
- •WBC no greater than 10,000/mm^3 OR
- •WBC no greater than 40,000/mm^3 that is stable for at least 1 week (may be sustained by hydroxyurea through the first week of study)
- •Bilirubin no greater than 1.5 mg/dL
- •ALT and AST no greater than 3 times upper limit of normal
- •Creatinine less than 2.0 mg/dL
- •Cardiovascular:
- •Ejection fraction at least 50% by MUGA
- •No myocardial infarction or unstable angina within the past 6 months
- •No prior unstable ventricular or supraventricular cardiac arrhythmias
- •HIV negative
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No other medical or psychiatric problem that would preclude study
- •Stratum I only:
- •No active infection requiring oral or IV antibiotics
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy:
- •Not specified
- •Chemotherapy:
- •See Disease Characteristics
- •At least 28 days since prior chemotherapy (except hydroxyurea)
- •At least 6 weeks since prior nitrosoureas
- •At least 8 weeks since prior UCN-01 (unless plasma UCN-01 level less than 1 uM)
- •Endocrine therapy:
- 另有 4 项未显示
排除标准
- 未提供