NCT00093821已完成1 期
A Multicenter Phase I Trial of 17-N-allylamino-17-demethoxy Geldanamycin (17-AAG, NSC #330507) in Patients With Recurrent/Refractory Pediatric Solid Tumors (Ewing's Sarcoma, Desmoplastic Small Round Cell Tumor, Osteosarcoma, Neuroblastoma, and Rhabdomyosarcoma) and Leukemia
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- MTD, defined as the highest dose level with an observed incidence of DLT in no more than 1 out of 6 patients treated at a particular dose level
研究概览
简要总结
This phase I trial is studying the side effects and best dose of tanespimycin in treating young patients with recurrent or refractory leukemia or selected solid tumors. Drugs used in chemotherapy, such as tanespimycin, work in different ways to stop cancer cells from dividing so they stop growing or die.
详细描述
PRIMARY OBJECTIVES:
I. Determine the dose-limiting toxicity and maximum tolerated dose (MTD) of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) in pediatric patients with recurrent or refractory leukemia or selected solid tumors.
II. Determine the levels of key proteins known to influence cancer cell survival and proliferation in patients treated with this drug at the MTD.
SECONDARY OBJECTIVES:
I. Determine the pharmacokinetics of this drug in these patients. II. Evaluate effects of genetic polymorphisms known to alter the activity of enzymes involved in the metabolism of 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
- — 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed diagnosis of 1 of the following malignancies:
- •Lymphoid, myeloid, or mixed lineage
- •Relapsed (in second or greater relapse) or refractory disease, confirmed by 1 of the following:
- •Bone marrow relapse, defined as either M3 bone marrow (> 25% blasts in the bone marrow aspirate) OR M2 bone marrow (5-25% blasts in the bone marrow aspirate) at any time after complete remission is attained
- •CNS relapse, defined as at least 5 WBC/mL by cytospin of any cerebrospinal fluid (CSF) specimen OR less than 5 WBC/mL by cytospin of 2 consecutive CSF specimens obtained >= 4 weeks apart and having definitive confirmation that blasts are derived from the original leukemic clone by molecular cytogenetics, multiparameter flow cytometry, or immunostaining of >= 2 antigens
- •Patients with underlying chronic myeloid leukemia must have > 25% blasts in the bone marrow aspirate
- •Patients with M3 bone marrow AND extramedullary sites of disease, other than leptomeningeal disease, are eligible
- •Solid tumor
- •One of the following tumor types:
- •Neuroblastoma
- •Ewing's sarcoma
- •Osteosarcoma
- •Desmoplastic small round cell tumor
- •Rhabdomyosarcoma
- •Progressed after prior standard therapy OR no effective standard therapy exists
- •Measurable or nonmeasurable disease
- •No known brain metastases
- •No active leptomeningeal leukemia, defined by the following criteria:
- •WBC > 5/mm^3 in cerebrospinal fluid (CSF)
- •Unequivocal confirmation of leukemic blasts in CSF by cell morphology
- •No symptomatic CNS disease (e.g., cranial nerve abnormalities) without cytologic abnormality in CSF
- •Performance status - Karnofsky 70-100% (for patients > 10 years of age)
- •Performance status - Lansky 70-100% (for patients =< 10 years of age)
- •More than 8 weeks
- •Absolute neutrophil count >= 750/mm^3
- •Platelet count >= 75,000/mm^3 (transfusion independent)
- •Hemoglobin >= 8.5 g/dL (transfusion allowed)
- •Bilirubin < 1.5 mg/dL
- •ALT and AST =< 2.5 times upper limit of normal (ULN)
- •INR =< 1.5 times ULN
- •Albumin > 2.0 g/dL
- •Creatinine =< 1.5 times ULN for age
- •Creatinine clearance or radioisotope glomerular filtration rate > 60 mL/min
- •Ejection fraction >= 50%
- •Shortening fraction >= 28%
- •QTc < 450 msec for men (470 msec for women)
- •No congenital long QT syndrome
- •LVEF > 40% by MUGA
- •No symptomatic congestive heart failure
- •No cardiac arrhythmia
- •No New York Heart Association class III or IV heart failure
- •No myocardial infarction within the past year
- •No uncontrolled dysrhythmias
- •No poorly controlled angina
- •More than 12 months since active ischemic heart disease
- •No history of serious ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation >= 3 beats in a row)
- •No left bundle branch block
- •No other significant cardiac disease
- •No pulmonary fibrosis by radiography
- •No ongoing or active bacterial or fungal infection
- 另有 27 项未显示
排除标准
- 未提供
研究组 & 干预措施
Treatment (tanespimycin)
Experimental
Patients receive tanespimycin IV over 2-6 hours on days 1, 4, 8, and 11 (for patients with solid tumors) OR days 1, 4, 8, 11, 15, and 18 (for patients with leukemia). Courses for all patients repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of tanespimycin until the 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. At least 15 patients are treated at the MTD.
干预措施: tanespimycin (Drug)
Treatment (tanespimycin)
Experimental
Patients receive tanespimycin IV over 2-6 hours on days 1, 4, 8, and 11 (for patients with solid tumors) OR days 1, 4, 8, 11, 15, and 18 (for patients with leukemia). Courses for all patients repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of tanespimycin until the 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. At least 15 patients are treated at the MTD.
干预措施: pharmacological study (Other)
Treatment (tanespimycin)
Experimental
Patients receive tanespimycin IV over 2-6 hours on days 1, 4, 8, and 11 (for patients with solid tumors) OR days 1, 4, 8, 11, 15, and 18 (for patients with leukemia). Courses for all patients repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of tanespimycin until the 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. At least 15 patients are treated at the MTD.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
MTD, defined as the highest dose level with an observed incidence of DLT in no more than 1 out of 6 patients treated at a particular dose level
时间窗: 21 days
次要结局
- Change in Hsp90 client protein levels in relation to dose of tanespimycin(Baseline to 21 days)
研究者
研究点 (1)
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