NCT00077467已完成1 期
A Phase I Study of PS-341 (Velcade, Bortezomib) in Pediatric Patients With Refractory/Recurrent Leukemias
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
- 36
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose and recommended phase II dose
研究概览
简要总结
This phase I trial is studying the side effects and best dose of bortezomib in treating young patients with refractory or recurrent leukemia. Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for their growth.
详细描述
OBJECTIVES: Primary I. Determine the maximum tolerated dose and recommended phase II dose of bortezomib in children with refractory or recurrent leukemia.
II. Determine the toxic effects of this drug in these patients. III. Determine the pharmacokinetics of this drug in these patients.
Secondary I. Determine, preliminarily, the antitumor activity of this drug in these patients.
II. Determine, preliminarily, the biologic activity of this drug in these patients.
OUTLINE: This is a dose-escalation, open-label, multicenter study.
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
- 1 Year 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed leukemia of 1 of the following types:
- •Acute lymphoblastic leukemia
- •Acute myeloid leukemia
- •Chronic myelogenous leukemia in blast crisis
- •Relapsed or refractory disease
- •Immunophenotypically confirmed disease, either at initial diagnosis or relapse
- •More than 25% blasts in the bone marrow (M3 bone marrow)
- •Active extramedullary disease (except leptomeningeal disease) allowed
- •No known curative therapy or therapy proven to prolong survival with an acceptable quality of life available
- •Performance status - Karnofsky 50-100% (for patients age 11 to 21)
- •Performance status - Lansky 50-100% (for patients age 10 and under)
- •Platelet count ≥ 20,000/mm^3*
- •Hemoglobin ≥ 8.0 g/dL*
- •WBC < 20,000/mm^3** (hydroxyurea for cytoreduction allowed)
- •No hyperleukocytosis (i.e., WBC > 100,000/mm^3)
- •Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- •ALT ≤ 5 times ULN
- •Albumin ≥ 2 g/dL
- •Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min
- •Creatinine based on age as follows:
- •≤ 0.8 mg/dL for patients age 5 and under
- •≤ 1.0 mg/dL for patients age 6 to 10
- •≤ 1.2 mg/dL for patients age 11 to 15
- •≤ 1.5 mg/dL for patients age 16 to 21
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No uncontrolled infection
- •Recovered from prior immunotherapy
- •At least 7 days since prior filgrastim (G-CSF) or sargramostim (GM-CSF)
- •At least 7 days since prior biologic agents
- •At least 3 months since prior stem cell transplantation or rescue and no evidence of active graft-versus-host disease
- •No concurrent prophylactic G-CSF during course 1 of study
- •No concurrent immunotherapy
- •No concurrent biologic therapy
- •Recovered from prior chemotherapy
- •At least 24 hours since prior hydroxyurea for cytoreduction
- •At least 6 weeks since prior nitrosoureas
- •No concurrent chemotherapy
- •At least 7 days since prior steroids (except as premedication prior to blood product transfusion)
- •Recovered from prior radiotherapy
- •At least 2 weeks since prior small port local palliative radiotherapy
- •At least 3 months since prior total body irradiation, craniospinal irradiation, or irradiation to more than 50% of the pelvis
- •At least 6 weeks since other prior substantial bone marrow radiotherapy
- •No concurrent radiotherapy
- •At least 7 days since prior retinoids
- •No other concurrent investigational agents
- •No other concurrent anticancer agents
- •No concurrent anticonvulsant medications known to activate the cytochrome p450 system (e.g., phenytoin, carbamazepine, or phenobarbital)
- •Concurrent benzodiazepines and gabapentin are allowed
排除标准
- 未提供
研究组 & 干预措施
Arm I
Experimental
Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: bortezomib (Drug)
Arm I
Experimental
Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacological study (Other)
Arm I
Experimental
Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Maximum tolerated dose and recommended phase II dose
时间窗: Up to 21 days
Toxicity as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) 3.0
时间窗: Up to 2 years
Pharmacokinetics as assessed by confidence intervals (CI), area under the curve (AUC), and half-life (T ½)
时间窗: Pretreatment, days 1, 8, 18-22 of course 1
次要结局
- Antitumor activity(Up to 2 years)
- Correlate apoptosis and NF-kB activation(Prestudy, days 8 and 18)
研究者
研究点 (1)
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