A Phase I Study Of Cloretazine™ (VNP40101M) And Temozolomide In Patients With Hematologic Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 25
- 试验地点
- 8
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy, such as temozolomide and VNP40101M, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Temozolomide may also help VNP40101M kill more cancer cells by making cancer cells more sensitive to the drug. Giving temozolomide together with VNP40101M may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and best dose of temozolomide and VNP40101M in treating patients with relapsed or refractory leukemias.
详细描述
OBJECTIVES:
- Determine the maximum tolerated dose of temozolomide and VNP40101M in patients with relapsed or refractory leukemias.
- Determine the toxic effects of this regimen in these patients.
OUTLINE: This is an open-label, dose-escalation, multicenter study.
Patients receive oral temozolomide twice daily on days 1-3 (for 5 doses) followed by VNP401010M IV over 15-60 minutes on day 3 (course 1). Patients achieving a complete or partial response or having ≥ 50% reduction in bone marrow blasts may receive a second course of therapy no earlier than day 43. Courses may be repeated approximately every 6 weeks at the discretion of the sponsor and in the absence of disease progression or unacceptable toxicity.
Cohorts of 6 patients receive escalating doses of temozolomide until a dose that depletes leukemic blast AGT in at least 4 of 6 patients is determined. Once this dose is determined, cohorts of 3-6 patients receive escalating doses of VNP401010M 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. Up to 10 patients are treated at the MTD.
研究设计
- 研究类型
- Interventional
- 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
- •DISEASE CHARACTERISTICS:
- •Diagnosis of 1 of the following:
- •Acute myeloid leukemia
- •Acute lymphoblastic leukemia
- •Chronic myelogenous leukemia in blast crisis
- •Relapsed or refractory disease
- •No known standard therapy that is anticipated to result in a durable remission exists
- •CNS leukemia allowed
- •PATIENT CHARACTERISTICS:
- •18 and over
- •Performance status
- •Life expectancy
- •Not specified
- •Hematopoietic
- •Not specified
- •Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- •ALT or AST ≤ 3 times ULN
- •Chronic hepatitis allowed
- •Creatinine ≤ 2.0 mg/dL
- •Cardiovascular
- •No active heart disease, including any of the following:
- •Myocardial infarction within the past 3 months
- •Symptomatic coronary artery disease
- •Arrhythmias not controlled by medication
- •Uncontrolled congestive heart failure
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception during and for 3 months after study participation
- •No uncontrolled active infection
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy
- •Not specified
- •Chemotherapy
- •Concurrent hydroxyurea allowed within the first 10 days of study drug administration for control of elevated blast levels or platelet counts
- •Maximum hydroxyurea dose 5 g daily
- •No persistent chronic toxic effects from prior chemotherapy > grade 1
- •Endocrine therapy
- •Not specified
- •Radiotherapy
- •Not specified
- •Not specified
- •Recovered from all prior therapy
- •At least 2 weeks since prior myelosuppressive cytotoxic agents (in the absence of rapidly progressive disease)
- •No more than 2 leukapheresis procedures within the first 10 days of study drug administration for control of elevated blast levels or platelet counts
- •No concurrent disulfiram
- •No other concurrent anticancer drugs
- •No other concurrent standard or investigational treatment for leukemia
排除标准
- 未提供