Phase I Study of Intrathecal Spartaject-Busulfan in Children With Neoplastic Meningitis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 28
- 试验地点
- 16
- 主要终点
- Toxicities of IT administered busulfan in children and adolescents with refractory CNS malignancies
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.
PURPOSE: Phase I trial to study the safety of delivering intrathecal busulfan in children and adolescents who have refractory CNS cancer and to estimate the maximum tolerated dose of this treatment regimen.
详细描述
OBJECTIVES:
- Determine the qualitative and quantitative toxicities of intrathecally administered busulfan in children and adolescents with refractory CNS malignancies.
- Determine the maximum tolerated dose of this treatment regimen in these patients.
- Determine the cerebrospinal fluid and serum pharmacokinetics of this treatment regimen in these patients.
- Determine the efficacy of this treatment regimen in these patients.
OUTLINE: This is a dose-escalation study.
Patients receive intrathecal busulfan twice a week, at least 3 days apart, for 2 weeks. Patients with complete or partial response or stable disease may continue therapy once a week for 2 weeks, once a week every other week for 2 treatments, and then once a month thereafter in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of busulfan 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 toxicities.
研究设计
- 研究类型
- Interventional
- 主要目的
- Treatment
入排标准
- 年龄范围
- 3 Years 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed CNS malignancy, including any of the following:
- •Primary malignant brain tumor refractory to standard therapy and metastatic to the cerebrospinal fluid (CSF) or leptomeningeal subarachnoid space
- •Recurrent or persistent leptomeningeal leukemia, lymphoma, or germ cell tumor refractory to conventional therapy
- •In second or greater relapse
- •CSF white blood count greater than 5 cells/mm3 with blasts on cytospin OR
- •Evidence of leptomeningeal tumor by MRI
- •No concurrent bone marrow disease
- •No obstruction or compartmentalization of CSF flow on CSF flow study
- •PATIENT CHARACTERISTICS:
- •Performance status:
- •Lansky 50-100% (under 10 years)
- •Karnofsky 50-100% (10 to 21 years)
- •Life expectancy:
- •Greater than 8 weeks
- •Hematopoietic:
- •Absolute neutrophil count greater than 1,000/mm^3
- •Platelet count greater than 75,000/mm^3
- •Bilirubin normal for age
- •ALT and AST less than 5 times upper limit of normal (ULN)
- •No hepatic disease
- •Creatinine no greater than 1.5 times ULN OR
- •Glomerular filtration rate greater than 70 mL/min
- •No renal disease
- •Cardiovascular:
- •No cardiac disease
- •No pulmonary disease
- •No uncontrolled infection
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy:
- •Not specified
- •Chemotherapy:
- •At least 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas)
- •At least 1 week since prior intrathecal chemotherapy (2 weeks for cytarabine) and recovered
- •Evidence of subsequent disease progression
- •Concurrent systemic chemotherapy allowed for recurrent disease after first course of treatment except for the following:
- •Chemotherapy targeted at leptomeningeal disease
- •Other phase I agent
- •Any agent that significantly penetrates the CSF (e.g., high dose methotrexate greater than 1 g/m2, thiotepa, high dose cytarabine, fluorouracil, IV mercaptopurine, nitrosoureas, or topotecan)
- •Any agent that causes serious unpredictable CNS side effects
- •Endocrine therapy:
- •Prior dexamethasone allowed with decreasing or stable dose at least one week before study
- •Concurrent dexamethasone or prednisone with chemotherapy regimen allowed
- •Radiotherapy:
- •At least 1 week since prior focal irradiation to the brain or spine
- •At least 8 weeks since prior craniospinal irradiation
- •No concurrent cranial or craniospinal irradiation
- 另有 2 项未显示
排除标准
- 未提供
结局指标
主要结局
Toxicities of IT administered busulfan in children and adolescents with refractory CNS malignancies
Maximum tolerated dose of IT administered busulfan
Serum and CSF pharmacokinetics of IT administered busulfan
次要结局
未报告次要终点