A Phase I Trial of CC-5013 (Lenalidomide) and CCI-779 in Patients With Relapsed or Refractory Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose (MTD) of temsirolimus when given together with lenalidomide
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 lenalidomide in treating patients with previously treated multiple myeloma. Lenalidomide may stop the growth of multiple myeloma by blocking blood flow to the cancer. Drugs used in chemotherapy, such as temsirolimus, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Temsirolimus may also stop the growth of cancer cells by blocking some of the enzymes needed for their growth. Giving lenalidomide together with temsirolimus may kill more cancer cells.
详细描述
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose of CCI-779 (temsirolimus) when given together with lenalidomide in patients with previously treated multiple myeloma.
SECONDARY OBJECTIVES:
I. Determine the toxicity of this regimen in these patients. II. Determine the clinical response of patients treated with this regimen. III. Determine the pharmacokinetics of this regimen. IV. Determine the pharmacodynamic effects of this regimen in these patients. V. Determine the effect of this regimen on immunological cellular and serological parameters and hematopoietic precursor cells.
OUTLINE: This is a dose-escalation study of CCI-779.
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
- •Diagnosis of multiple myeloma (MM)
- •Salmon-Durie stage IIA or IIIA
- •No stage B disease
- •Meets ≥ 1 major AND 1 minor criterion OR ≥ 3 minor criteria
- •The following are considered major criteria:
- •Plasmacytoma on tissue biopsy
- •Bone marrow plasmacytosis with ≥ 30% plasma cells
- •Monoclonal paraprotein ≥ 3,500 mg/dL (IgG) or ≥ 2,000 mg/dL (IgA) OR monoclonal protein (Bence-Jones protein) ≥ 1,000 mg by 24-hour urine collection
- •The following are considered minor criteria:
- •Bone marrow plasmacytosis 10-29% of marrow cellularity
- •Monoclonal globulin spike < 3,500 mg/dL (IgG) or < 2,000 mg/dL (IgA)
- •Lytic bone lesions
- •Decrease in normal IgM (< 50 mg/dL), IgA (< 100 mg/dL), or IgG (< 600 mg/dL)
- •Disease progression after ≥ 1 prior systemic treatment regimen* for MM (e.g., chemotherapy, high-dose corticosteroids, thalidomide, or bortezomib), defined as > 25% increase in serum or urine M-protein
- •No solitary plasmacytoma
- •No non-secretory MM (absent serum or urinary M-protein)
- •ECOG performance status 0-2
- •Life expectancy > 6 months
- •Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- •AST and ALT ≤ 3 times ULN
- •Creatinine ≤ 2.0 mg/dL
- •Absolute neutrophil count ≥ 1,500/mm³
- •Platelet count ≥ 100,000/mm³
- •Fasting cholesterol ≤ 350 mg/dL
- •Fasting triglycerides ≤ 400 mg/dL
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective double-method contraception
- •Must agree not to donate blood, sperm, or ova during and for 4 weeks after completion of study treatment
- •No other prior or concurrent malignancy or myelodysplasia except for the following:
- •Basal cell or squamous cell skin cancer
- •Carcinoma in situ of the cervix
- •Localized cancer treated with surgery only with no evidence of disease for > 5 years
- •No history of recurrent deep vein thrombosis (DVT)/pulmonary embolism (PE) or DVT/PE occurring while on therapeutic levels of anticoagulation
- •Patients with DVT/PE within the past 6 months are eligible provided they receive full anticoagulation during study treatment
- •No active infection requiring oral or intravenous antibiotics
- •No uncontrolled illness including, but not limited to, any of the following:
- •Ongoing or active infection
- •Symptomatic congestive heart failure
- •Unstable angina pectoris
- •Cardiac arrhythmia
- •Psychiatric illness or social situations that would preclude study compliance
- •No known hepatitis B or C
- •No history of allergic reactions attributed to compounds of similar chemical or biologic composition to lenalidomide or CCI-779
- •See Disease Characteristics
- •Prior lenalidomide allowed
- •Prior high-dose chemotherapy with stem cell transplantation allowed
- •More than 4 weeks since prior chemotherapy or other antimyeloma systemic therapy (e.g., thalidomide, bortezomib, or high-dose corticosteroids) and recovered
- •No prior exposure to both lenalidomide and mTOR inhibitors (given together)
- •Treatment with single-agent lenalidomide or single-agent mTOR inhibitor allowed
- 另有 5 项未显示
排除标准
- 未提供
研究组 & 干预措施
Treatment (antiangiogenesis, chemotherapy, enzyme inhibitor)
Patients receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22 and oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.
干预措施: lenalidomide (Drug)
Treatment (antiangiogenesis, chemotherapy, enzyme inhibitor)
Patients receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22 and oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.
干预措施: temsirolimus (Drug)
Treatment (antiangiogenesis, chemotherapy, enzyme inhibitor)
Patients receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22 and oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.
干预措施: pharmacological study (Other)
Treatment (antiangiogenesis, chemotherapy, enzyme inhibitor)
Patients receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22 and oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 12 courses 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 (MTD) of temsirolimus when given together with lenalidomide
时间窗: Course 1 (first 28 days)
The MTD is the dose level at which less than 2 out of 6 patients experience dose limiting toxicities (DLT). The National Cancer Institute Common Terminology Criteria for Adverse events (CTCAE) version 3.0 will used to characterize toxicities.
次要结局
- Toxicity of lenalidomide and temsirolimus combination therapy in previously treated mulple myeloma patients(From the time of their first treatment with lenalidomide and temsirolimus)
- Pharmacodynamics of temsirolimus in peripheral blood mononuclear cells (PBMC)(Days 1 and 8 of course 1)
- Assessment of serum cytokines; IL-2, sIL-2R, TNF-alpha, IFN-gamma, IL-1 beta, IL-1Ra, GM-CSF, IL-8, IL-6, sIL-6R, MIP-1 alpha, VEGF, and b-FGF(Baseline and then every 4 weeks)
- Assessment of peripheral blood immune cell subsets(Baseline and then every 4 weeks)
- Pharmacokinetic analysis of lenalidomide(Baseline and days 1 and 22 (lenalidomide only) of course 1)