Arsenic Trioxide, High-Dose Cytarabine and Idarubicin Induction Therapy in Previously Untreated de Novo and Secondary Adult Acute Myeloid Leukemia Patients < 60 Years Old - A Phase I Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 61
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose and/or biologically effective dose or arsenic trioxide
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy, such as arsenic trioxide, cytarabine, and idarubicin, work in different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and best dose of arsenic trioxide when given together with cytarabine and idarubicin in treating patients with acute myeloid leukemia.
详细描述
OBJECTIVES:
- Determine the maximum tolerated dose and/or biologically effective dose of arsenic trioxide followed by high-dose cytarabine and idarubicin in patients with previously untreated de novo or secondary acute myeloid leukemia.
OUTLINE: This is a dose-escalation study of arsenic trioxide. Patients are stratified according to timing of accrual (before November 2002 vs since November 2002).
Patients receive arsenic trioxide IV over 1 hour on day 1 followed by high-dose cytarabine IV over 1 hour every 12 hours on days 1-6 and idarubicin IV over 30 minutes on days 2-4 (immediately after doses 3, 5 and 7 of cytarabine). Patients also receive filgrastim (G-CSF) subcutaneously beginning 12 hours after the last dose of chemotherapy and continuing until blood counts recover.
Cohorts of 3-6 patients receive escalating doses of arsenic trioxide until the maximum tolerated dose (MTD), current dose used for myelodysplastic syndromes or acute promyelocytic leukemia, or biologically effective dose is reached. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. The biologically effective dose is defined as the dose at which 3 patients with constitutive STAT3 activity have the activity negated after the first dose of arsenic trioxide.
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 59 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed de novo or secondary acute myeloid leukemia with ≥ 20% blasts AND at least 1 of the following characteristics*:
- •Auer rods
- •Peroxidase or sudan black positive blasts
- •Chloroacetate esterase-positive or diffusely non-specific esterase-positive blasts
- •Presence of a myeloid immunophenotype by multiparameter flow cytometry, including expression of one or more myeloid markers (CD13, CD33) on blasts NOTE: *Megakaryocytic leukemia can be diagnosed by the detection of platelet antigens (e.g. factor VIII, glycoprotein Ib or IIb/IIIa) using monoclonal antibodies or the presence of ultrastructural platelet peroxidase
- •No acute promyelocytic leukemia
- •No Philadelphia-chromosome positive chronic myeloid leukemia
- •Prior hematologic disorders, including myelodysplastic syndromes, aplastic anemia, paroxysmal nocturnal hemoglobinuria, and myeloproliferative disorders allowed
- •PATIENT CHARACTERISTICS:
- •Performance status
- •Not specified
- •Life expectancy
- •More than 4 weeks
- •Hematopoietic
- •Not specified
- •Bilirubin ≤ 2 times normal*
- •SGOT ≤ 2 times normal*
- •Alkaline phosphatase ≤ 2 times normal* NOTE: *Unless abnormalities are directly attributable to leukemia
- •Creatinine ≤ 1.5 times normal* NOTE: *Unless abnormalities are directly attributable to leukemia
- •Cardiovascular
- •Cardiac ejection fraction ≥ 45%*
- •Absolute QT interval ≤ 460 msec with potassium > 4.0 mEq/L and magnesium > 1.8 mg/dL
- •No myocardial infarction within the past 6 months
- •No uncontrolled symptomatic congestive heart failure
- •No angina pectoris
- •No multifocal cardiac arrythmias
- •No other severe cardiovascular disease NOTE: *Unless abnormalities are directly attributable to leukemia
- •No serious medical or psychiatric illness that would preclude informed consent or limit survival to < 4 weeks
- •No uncontrolled diabetes mellitus
- •No other concurrent active malignancy
- •No known hypersensitivity to E. coli-derived drug preparations
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception during and for 3 months after study participation
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy
- •Not specified
- •Chemotherapy
- •No prior chemotherapy for acute leukemia, except hydroxyurea to control white blood cell counts
- •Prior chemotherapy for an antecedent malignancy or other medical condition allowed
- •Endocrine therapy
- •Not specified
- •Radiotherapy
- •Prior radiotherapy for an antecedent malignancy or other medical condition allowed
- •Not specified
排除标准
- 未提供
结局指标
主要结局
Maximum tolerated dose and/or biologically effective dose or arsenic trioxide
时间窗: 30 days after completion of study treatment
次要结局
未报告次要终点