Phase I Trial of Intravenous Fenretinide (4-HPR) for Patients With Hematologic Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 29
- 试验地点
- 8
- 主要终点
- To determine the maximum tolerated dose of fenretinide
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy, such as fenretinide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving fenretinide in a different way may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and best dose of intravenous fenretinide in treating patients with refractory or relapsed hematologic cancer.
详细描述
OBJECTIVES:
- Determine the maximum tolerated dose of intravenous emulsified fenretinide in patients with refractory or relapsed hematologic malignancies.
- Determine the toxic effects of this drug in these patients.
- Determine the pharmacokinetics and in vivo activity of this drug in these patients.
- Determine, preliminarily, disease or tumor response in patients treated with this drug.
OUTLINE: This is a pilot, dose-escalation, multicenter study.
Patients receive emulsified fenretinide IV continuously over 5 days. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve a complete or partial response may continue to receive fenretinide at the discretion of the study chair.
Cohorts of 1 patient receive accelerated escalating doses of fenretinide until 2 patients experience moderate toxicity (cumulative across all dose levels) OR 1 patient experiences dose-limiting toxicity (DLT). After completion of the accelerated dose-escalation portion, the standard dose-escalation portion begins. Cohorts of 3-6 patients receive escalating doses of fenretinide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience DLT. At least 6 patients are treated at the MTD. An additional 12 patients are treated at the MTD.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 120 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Histologically or cytologically confirmed diagnosis of 1 of the following hematologic malignancies:
- •Non-Hodgkin's lymphoma (NHL)
- •Hodgkin's lymphoma
- •Multiple myeloma
- •Acute lymphoblastic leukemia
- •Acute myeloid leukemia
- •Chronic hematologic malignancy with a poor prognosis (e.g., failed 3 prior standard therapies), including any of the following:
- •Chronic lymphocytic leukemia
- •Chronic myelogenous leukemia
- •Indolent NHL
- •Myeloproliferative disorders
- •Refractory or relapsed disease, as defined by 1 of the following:
- •Resistant to standard therapy for refractory or relapsed disease
- •Progressed after standard therapy for advanced disease
- •No effective treatment exists
- •Measurable or evaluable disease
- •No active CNS disease
- •Previously treated leptomeningeal disease or brain metastases allowed provided there is no evidence of remaining cancer by positron-emission tomography, MRI, or spinal fluid cytology
- •PATIENT CHARACTERISTICS:
- •18 and over
- •Performance status
- •Life expectancy
- •At least 3 months
- •Hematopoietic
- •Absolute neutrophil count ≥ 1,500/mm^3 (unless due to bone marrow involvement of disease)
- •Platelet count ≥ 75,000/mm^3 (unless due to bone marrow involvement of disease)
- •Hemoglobin ≥ 8.0 g/dL (transfusion allowed)
- •No coagulation disorders
- •AST and ALT < 2.5 times upper limit of normal (ULN) (≤ 5 times ULN for patients with liver metastasis)
- •Bilirubin ≤ 1.5 times ULN
- •Creatinine ≤ 1.5 times ULN
- •Cardiovascular
- •No major cardiovascular disease
- •No major respiratory disease
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective double-method contraception prior to study entry, during study, and for at least 6 months after study participation
- •No uncontrolled systemic infection
- •No uncontrolled hypertriglyceridemia (i.e., triglyceride level > 500 mg/dL)
- •No known HIV positivity
- •No known allergy to egg products
- •No known familial hyperlipidemia disorders
- •No previously undiscovered hypertriglyceridemia
- •No poorly controlled diabetes
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy
- •Not specified
- •Chemotherapy
- •More than 2 weeks since prior chemotherapy except hydroxyurea
- 另有 34 项未显示
排除标准
- 未提供
结局指标
主要结局
To determine the maximum tolerated dose of fenretinide
时间窗: participants will be followed for the duration of cycle 1, which is expected to be 3 weeks.
To describe the toxicities of fenretinide
时间窗: participants will be followed for the duration of treatment, which is expected to be 18 weeks or less
次要结局
未报告次要终点