A Phase I Study of Intravenous (Emulsion) Fenretinide (4-HPR, NSC 374551) in Children With Recurrent or Resistant Acute Lymphoblastic Leukemia (ALL), Acute Myelogenous Leukemia (AML), and Non-Hodgkin's Lymphoma (NHL) IND #70,058"
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 3
- 试验地点
- 2
- 主要终点
- Determine plasma pharmacokinetics
研究概览
简要总结
The purposee of this study is to determine the safety and dosing of Fenretinide when given continuously for 5 days, every 3 weeks, in pediatric patients with recurrent and/or resistant acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), and non-Hodgkin's lymphoma (NHL).
详细描述
Fenretinide is a cytotoxic retinoid that has activity against a variety of cell lines in vitro in a dose-related manner. The exact mechanism of fenretinide cytotoxicity in leukemia and lymphoma cell lines is not known, but may include the de novo ceramide synthesis of ceramides and the generation of reactive oxygen species. The malignancy-specific nature of fenretinide-induced ceramides suggests that combinations of the drug with other ceramide modulating agents may have a favorable therapeutic index.
In this study, the primary aims are to define the maximum tolerated dose, toxicity profile, and pharmacokinetics of IV fenretinide when given continuously in pediatric patients with ALL, AML, and NHL. The drug will be administered via a central venous or percutaneous indwelling central catheter in an inpatient hospital setting.
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
- •Diagnosed with relapsed or refractory ALL, AML, or NHL
- •Must have had two or more therapeutic attempts for treating/curing disease
- •Must have fully recoved from acute toxic effects of all prior therapy
- •Karnofsky of greater than 50% for older than 10 years of age and Lansky greater than 50% for younger than 10 years.
排除标准
- •Grade 2 Pruritus or Rash (all forms)
- •Grade 3 Dry Skin that is refractory to topical medical management
- •Cardiac Fractional Shortening < 27% on echocardiogram
- •Left Ventricular Ejection Fraction < 45% on echocardiogram
- •Known allergy to egg products or soy bean oil
- •Renal, Liver, and Pancreatic function:
- •serum creatinine > 1.5X ULN
- •direct bilirubin > 1.5X ULN
- •ALT or AST > 2.5X ULN
- •Serum trigylcerides > 2.5X ULN for age
- •Lipase > 1.5X ULN for age
- •History of pancreatitis
研究组 & 干预措施
Combination of Fenretinide, Cytarabine, and Methotrexate
IV for 7 days for each 21 day cycle
干预措施: Fenretinide (Drug)
Combination of Fenretinide, Cytarabine, and Methotrexate
IV for 7 days for each 21 day cycle
干预措施: Cytarabine (Drug)
Combination of Fenretinide, Cytarabine, and Methotrexate
IV for 7 days for each 21 day cycle
干预措施: Methotrexate (Drug)
结局指标
主要结局
Determine plasma pharmacokinetics
时间窗: end of study
Determine maximum tolerated dose
时间窗: end of study
Define systemic toxicities
时间窗: end of study
次要结局
- Determine the response rate to IV Fenretinide(end of study)
- Determine bioavailability of fenretinide and metabolites(end of study)