Microarray Analysis of the Effect of Cyclosporine Therapy on Gene Expression Patterns in Large Granular Lymphocytic Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Changes in Gene Expression Patterns
研究概览
简要总结
Background:
- Large granular lymphocyte (LGL) leukemia is a low-grade non-Hodgkin's lymphoma.
- LGL is associated with low numbers of white blood cells (leading to recurring infections), red blood cells (causing anemia) and platelets (causing abnormal bleeding).
- Cyclosporine (CSA) is an immunosuppressive drug that improves low blood cell counts in about 50 percent of patients with LGL leukemia.
Objectives:
- To identify what factors determine why cyclosporine works in some patients and not in others.
- To identify what causes low blood counts in LGL leukemia.
Eligibility: Patients 18 years of age and older with LGL leukemia.
Design:
- Patients have a medical history, physical examination blood tests, bone marrow biopsy and x-ray studies, including chest x-rays and computed tomography (CT) scans of the chest, abdomen and pelvis. Patients with an easily accessible enlarged lymph node have a node biopsy (removal of a small piece of tissue for microscopic examination).
- Patients take cyclosporine twice a day by mouth. Blood samples are taken at least weekly to adjust the cyclosporine dosing to maintain therapeutic serum levels.
- Patients undergo apheresis (collection of white blood cells) at a number of different time points in the study (maximum 6 times) to look at the differences in the leukemia cells before and during treatment with cyclosporine. For apheresis, blood is withdrawn through a needle in an arm vein and directed through a catheter (plastic tube) into a machine that separates it into its components. The white cells are extracted and the rest of the blood is returned through the same needle or through a second needle in the other arm.
详细描述
Background:
- LGL leukemia is a low grade non-Hodgkins Lymphoma characterized by tissue invasion of the marrow, spleen and liver
- Recurrent infections due to chronic neutropenia and transfusion-dependent anemia are the principal causes for initiation of therapy
- Approximately 50% of patients treated with cyclosporine (CSA) respond to treatment. CSA appears to correct the associated cytopenia without decreasing LGL numbers, suggesting it may inhibit LGL secretion of yet unidentified mediators of neutropenia and anemia.
- Analysis of differential gene expression profiles in patients with LGL leukemia treated with cyclosporine has the potential to detect as yet unidentified, therapeutic targets and possibly provide predictors of CSA responsiveness.
Objective:
- Identify changes in gene expression patterns induced by cyclosporine therapy in patients with LGL leukemia
- Identify differences between responding and non-responding patients
Eligibility:
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
LGL Patients administered cyclosporine
Large Granular Lymphocyte Leukemia (LGL) is a low grade non-Hodgkins lymphoma characterized by tissue invasion of the marrow, spleen, and liver. Cyclosporine 5-10 mg/kg/day was administered as an oral preparation given every 12 hours. Doses are adjusted to maintain a therapeutic level between 200-400 ng/ml.
干预措施: Cyclosporine (Drug)
LGL Patients administered cyclosporine
Large Granular Lymphocyte Leukemia (LGL) is a low grade non-Hodgkins lymphoma characterized by tissue invasion of the marrow, spleen, and liver. Cyclosporine 5-10 mg/kg/day was administered as an oral preparation given every 12 hours. Doses are adjusted to maintain a therapeutic level between 200-400 ng/ml.
干预措施: Gene expression analysis (Genetic)
LGL Patients administered cyclosporine
Large Granular Lymphocyte Leukemia (LGL) is a low grade non-Hodgkins lymphoma characterized by tissue invasion of the marrow, spleen, and liver. Cyclosporine 5-10 mg/kg/day was administered as an oral preparation given every 12 hours. Doses are adjusted to maintain a therapeutic level between 200-400 ng/ml.
干预措施: Microarray analysis (Genetic)
LGL Patients administered cyclosporine
Large Granular Lymphocyte Leukemia (LGL) is a low grade non-Hodgkins lymphoma characterized by tissue invasion of the marrow, spleen, and liver. Cyclosporine 5-10 mg/kg/day was administered as an oral preparation given every 12 hours. Doses are adjusted to maintain a therapeutic level between 200-400 ng/ml.
干预措施: Laboratory biomarker analysis (Other)
结局指标
主要结局
Changes in Gene Expression Patterns
时间窗: Baseline and 12 weeks
The goal was to examine which genes had a 2-fold gene expression between pre-treatment (baseline) and post treatment (12 weeks). Genes significant at the 0.001 level will be considered as differentially expressed due to treatment.
次要结局
- Number of Participants With Adverse Events(3 months)
研究者
Thomas Waldmann, M.D.
Principal Investigator
National Institutes of Health Clinical Center (CC)