A Phase 1 Study of CCI-779 in Combination With Dexamethasone in Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose of temsirolimus
研究概览
简要总结
This phase I trial is studying the side effects and best dose of temsirolimus when given together with dexamethasone in treating patients with recurrent or refractory multiple myeloma. Temsirolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving temsirolimus together with dexamethasone may kill more cancer cells.
详细描述
PRIMARY OBJECTIVES:
I. To assess the toxicity and safety of temsirolimus in combination with dexamethasone in patients with recurrent or refractory multiple myeloma.
II. To assess a dose of temsirolimus that is capable of inhibiting the mammalian target of rapamycin (mTOR) in myeloma tumor cells.
SECONDARY OBJECTIVES:
I. To assess the efficacy of temsirolimus in combination with dexamethasone in these patients.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Pathologically confirmed multiple myeloma
- •Measurable levels of M protein in serum and/or urine
- •Recurrent or refractory disease
- •Progressive disease after treatment with ≥ 2 separate chemotherapeutic regimens
- •At least 1 of the regimens must have included high-dose dexamethasone (40 mg on days 1-4, 9-12, and 17-20) or medium-dose dexamethasone (40 mg on days 1, 8, 15, and 22) of a 28-day course
- •ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
- •Life expectancy ≥ 8 weeks
- •Absolute neutrophil count > 1,000/mm^3
- •Platelet count > 100,000/mm ^3
- •Total bilirubin < 2 mg/dL
- •AST and ALT < 3 times upper limit of normal
- •Creatinine < 2 mg/dL
- •Fasting cholesterol < 350 mg/dL
- •Fasting triglycerides < 400 mg/dL
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No history of allergic reactions attributed to compounds of similar chemical or biological composition to temsirolimus or dexamethasone
- •No concurrent uncontrolled illness including, but not limited to, any of the following:
- •Ongoing or active infection
- •Poorly controlled hypertension
- •Diabetes mellitus
- •Symptomatic congestive heart failure
- •Unstable angina pectoris
- •Cardiac arrhythmia
- •Psychiatric illness or social situation that would limit compliance with study requirements
- •See Disease Characteristics
- •At least 4 weeks since prior cytotoxic therapy
- •More than 4 weeks since prior chemotherapy and recovered
- •No concurrent anticonvulsive or antiarrhythmic medications
- •No concurrent enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine, or phenobarbital) or other CYP3A4 inhibitors or inducers (e.g., rifampin or Hypericum perforatum [St. John wort])
- •No concurrent prophylactic hematopoietic colony-stimulating factors
- •No other concurrent investigational therapy
- •No other concurrent anticancer therapy
排除标准
- 未提供
研究组 & 干预措施
Treatment (enzyme inhibitor, chemotherapy)
Patients receive temsirolimus IV over 30 minutes once weekly on days 1, 8, 15, and 22 and oral dexamethasone once on days 1, 2, 8, 9, 15, 16, 22, and 23. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: dexamethasone (Drug)
Treatment (enzyme inhibitor, chemotherapy)
Patients receive temsirolimus IV over 30 minutes once weekly on days 1, 8, 15, and 22 and oral dexamethasone once on days 1, 2, 8, 9, 15, 16, 22, and 23. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: temsirolimus (Drug)
Treatment (enzyme inhibitor, chemotherapy)
Patients receive temsirolimus IV over 30 minutes once weekly on days 1, 8, 15, and 22 and oral dexamethasone once on days 1, 2, 8, 9, 15, 16, 22, and 23. Courses repeat every 28 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 of temsirolimus
时间窗: Course 1 (first 28 days)
The MTD is the dose level at which less than 2 out of 6 subjects experience DLT. Assessed according to the NCI Common Toxicity Criteria (CTC).
Toxicity and safety
时间窗: Continuously from start of treatment study
The description and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for AE reporting.
次要结局
- Correlation between response to treatment with temsirolimus and the degree of p70 inhibition in peripheral blood mononuclear cells and in multiple myeloma (MM) cells(Every 4 weeks)
- Correlation between response to treatment with temsirolimus and the degree of pre-treatment AKT activation in MM cells(Every 4 weeks)
- Correlation between response to treatment with temsirolimus and the degree of PTEN expression in MM cells(Every 4 weeks)
- Correlation between response to treatment with temsirolimus and the presence of RAS mutations(Every 4 weeks)
- Correlation between response to treatment with temsirolimus and the presence of myc mutations(Every 4 weeks)