A Phase I Trial Of Sequential Administration Of Triapine (3-Aminopyridine-2-Carboxaldehyde Thiosemicarbazone) Followed By Fludarabine In Adults With Relapsed And Refractory Leukemias And Myelodysplasias
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 试验地点
- 4
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy, such as fludarabine, work in different ways to stop cancer cells from dividing so they stop growing or die. 3-AP may help fludarabine kill more cancer cells by making them more sensitive to the drug.
PURPOSE: This phase I trial is studying the side effects and best dose of fludarabine when given together with 3-AP in treating patients with relapsed or refractory acute leukemia, chronic leukemia, or high-risk myelodysplastic syndrome.
详细描述
OBJECTIVES:
- Determine the feasibility and tolerability of 3-AP (Triapine^® ) followed by fludarabine in patients with relapsed or refractory acute or chronic leukemia or high-risk myelodysplastic syndromes.
- Determine the toxic effects of this regimen in these patients.
- Determine the maximum tolerated dose of this regimen in these patients.
OUTLINE: This is a multicenter, dose-escalation study of fludarabine. Patients are stratified according to disease (acute leukemias and myelodysplastic syndromes [MDS] vs chronic lymphocytic leukemia and prolymphocytic leukemia). Patients are assigned to 1 of 2 treatment groups.
- Group 1 (chronic lymphocytic leukemia or prolymphocytic leukemia): Patients receive 3-AP (Triapine^®) IV over 4 hours and fludarabine IV over 30 minutes on days 1-5.
Cohorts of 3-6 patients receive escalating doses of fludarabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 10 additional patients are treated at that dose level.
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:
- •Histologically confirmed diagnosis of 1 of the following:
- •High-risk myelodysplastic syndromes (MDS), including refractory anemia with excess blasts and chronic myelomonocytic leukemia
- •International Prognostic Scoring System (IPSS) score at least 1.5 based on the following:
- •More than 10% marrow blasts
- •Cytopenias in at least 2 lineages
- •Adverse cytogenetics
- •Acute myeloid leukemia (AML)
- •All subtypes, including MDS/AML and treatment-related (secondary) AML
- •Acute lymphoblastic leukemia
- •Acute progranulocytic leukemia
- •Ineligible for arsenic therapy
- •Chronic myelogenous leukemia
- •Accelerated phase or blastic crisis
- •Chronic lymphocytic leukemia
- •Prolymphocytic leukemia
- •Received or ineligible for established curative regimens, including stem cell transplantation
- •Acute and chronic leukemias must be relapsed and/or refractory with progressive disease since last therapy
- •PATIENT CHARACTERISTICS:
- •18 and over
- •Performance status
- •Life expectancy
- •Not specified
- •Hematopoietic
- •No history of hemolytic anemia grade 2 or greater
- •No known glucose-6-phosphate dehydrogenase (G6PD) deficiency
- •G6PD screening required for high-risk groups (i.e., patients of African, Asian, or Mediterranean origin/ancestry)
- •SGOT and SGPT no greater than 2.5 times normal
- •Bilirubin no greater than 2 mg/dL
- •No chronic hepatitis
- •Creatinine normal OR
- •Creatinine clearance at least 60 mL/min
- •Cardiovascular
- •No active heart disease
- •No myocardial infarction within the past 3 months
- •No severe coronary artery disease
- •No arrhythmias (other than atrial flutter or fibrillation) requiring medication
- •No uncontrolled congestive heart failure
- •No dyspnea at rest or with minimal exertion
- •No severe pulmonary disease requiring supplemental oxygen
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No neuropathy grade 2 or greater
- •No active uncontrolled infection
- •Infections under active treatment and controlled by antibiotics are allowed
- •No other life-threatening illness
- •No psychiatric illness that would preclude study compliance
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy
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排除标准
- 未提供