Phase I Study of 5-Aza-2'-Deoxycytidine (Decitabine) as a Biologic Modifier of Retinoid Responsive Genes in Patients With High-Risk Myelodysplastic Syndromes and Acute Myelogenous Leukemia (De-novo, Relapsed or Secondary)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose (MTD) of decitabine, graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0
研究概览
简要总结
This phase I trial is studying the side effects and best dose of decitabine in treating patients with myelodysplastic syndromes or acute myeloid leukemia. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.
详细描述
OBJECTIVES:
I. Determine the maximum tolerated dose of decitabine in patients with high-risk myelodysplastic syndromes or acute myeloid leukemia.
II. Determine the minimum effective dose of this drug that produces demethylation of DNA with tolerable toxicity in these patients.
III. Determine the minimum effective dose of this drug that augments in vitro responses to retinoids.
IV. Determine the pharmacokinetics of this drug in these patients. V. Determine the clinical response rate of patients treated with this drug.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •One of the following diagnoses:
- •High-risk myelodysplastic syndromes (MDS)
- •Acute myeloid leukemia (AML)
- •De novo, secondary, or relapsed disease
- •Any number of prior regimens for primary or relapsed disease
- •Ineligible for or refuses aggressive management
- •Measurable disease, defined as:
- •More than 5% blasts in bone marrow of patients with MDS
- •More than 30% blasts in bone marrow of patients with AML
- •Involvement of cerebrospinal fluid allowed
- •Performance status - ECOG 0-2
- •Performance status - Karnofsky 60-100%
- •See Disease Characteristics
- •Bilirubin no greater than 1.25 times upper limit of normal (ULN)
- •AST and/or ALT no greater than 1.25 times ULN
- •Creatinine less than 1.7 mg/dL
- •Creatinine clearance at least 60 mL/min
- •No symptomatic congestive heart failure
- •No unstable angina pectoris
- •No cardiac arrhythmia
- •No ongoing or active infection
- •No other uncontrolled illness that would preclude study participation
- •No psychiatric illness or social situation that would preclude study compliance
- •No prior allergic reactions to compounds of similar chemical or biological composition to decitabine
- •No other active malignancy
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •At least 4 weeks since prior biologic therapy (e.g., interferon, filgrastim [G-CSF], sargramostim [GM-CSF], thrombopoietin, or epoetin alfa)
- •No concurrent hematopoietic growth factors (GM-CSF, thrombopoietin, or epoetin alfa)
- •No concurrent prophylactic G-CSF
- •Prior intrathecal cytarabine allowed for patients with cerebrospinal fluid involvement
- •At least 4 weeks since prior chemotherapy (except low-dose chemotherapy administered to maintain WBC counts) (6 weeks for nitrosoureas or mitomycin) and recovered
- •At least 24 hours since prior hydroxyurea
- •Concurrent intrathecal cytarabine allowed for patients with cerebrospinal fluid involvement
- •No prior radiotherapy greater than 3,000 cGy to marrow-producing areas
- •At least 4 weeks since prior radiotherapy and recovered
- •Prior investigational therapy allowed
- •No other concurrent investigational agents
- •No concurrent combination antiretroviral therapy for HIV-positive patients
- •No other concurrent anticancer therapy
排除标准
- 未提供
研究组 & 干预措施
Treatment (decitabine)
Patients receive decitabine IV over 3 hours twice daily OR IV over 1 hour once daily on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of decitabine until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.
干预措施: decitabine (Drug)
Treatment (decitabine)
Patients receive decitabine IV over 3 hours twice daily OR IV over 1 hour once daily on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of decitabine until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.
干预措施: laboratory biomarker analysis (Other)
Treatment (decitabine)
Patients receive decitabine IV over 3 hours twice daily OR IV over 1 hour once daily on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of decitabine until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.
干预措施: pharmacological study (Other)
结局指标
主要结局
Maximum tolerated dose (MTD) of decitabine, graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0
时间窗: Up to day 28
次要结局
- Changes in gene expression, gene methylation and bone marrow aspirate sample measurements(Up to day 5)
- Minimal effective dose of decitabine that will lead to demethylation of deoxyribonucleic acid (DNA) with tolerable toxicity as assessed by RXR gene(Up to day 28)
- Proportion of patients with in-vitro retinoid response(Up to 8 years)
- Duration of clinical response(Up to 8 years)