Circulating Cell-free Tumor DNA and Metabolites in Cerebrospinal Fluid as Early Biomarkers of Secondary CNS Involvement in Diffuse Large B-cell Lymphoma
试验速览
- 阶段
- 不适用
- 入组人数
- 75
- 试验地点
- 1
- 主要终点
- CSF tumor cfDNA and metabolite detectability and cytological/flow cytometric confirmation of CNS lymphoma at the time of diagnosis and relapse
研究概览
简要总结
The study is a prospective clinical study which investigates the use of new diagnostic methods to localize aggressive lymphoma involving the central nervous system(CNS). By measuring cell-free tumor DNA and metabolomics in cerebrospinal fluid and blood in patients with systemic Diffuse Large B-cell Lymphoma the investigators aim to improve the diagnostic certainty of an impending relapse of lymphoma in CNS.
详细描述
Diffuse Large B-cell Lymphoma is a malignant, aggressive cancer representing 40% of Non-Hodgkin Lymphomas globally. The risk of relapse after primary treatment is approximately 30% of which up to 10 % occurs in the central nervous system (CNS). The prognosis after CNS relapse is severely discouraging with an overall survival of 3-6 months. Currently CNS relapse is diagnosed by either flow cytometry performed on cerebrospinal fluid or a stereotactic biopsy based on tumor localization by an MRI scan. Both diagnostic methods however require a certain tumor mass in order avoid false negative test results.
The purpose of this study is to learn whether tumor-derived cell-free circulating DNA (cfDNA) and/or metabolite profiles from diffuse large B-cell lymphoma (DLBCL) cells can be identified in the cerebrospinal fluid (CSF), before the malignant cells themselves are detectable in CSF. Thus the investigators aim to investigate the diagnostic potential of cfDNA and/or metabolites measured in blood and cerebrospinal fluid. The study is based on the following four hypotheses:
Hypothesis 1: Measurement of cfDNA and/or metabolites in CSF are more sensitive methods of detecting DLBCL involvement in CNS compared to conventional diagnostics.
Hypothesis 2: Quantitative cfDNA/metabolomics in CSF has independent prognostic value in DLBCL.
Hypothesis 3: cfDNA and/or metabolite profile in CSF detected at primary diagnosis predicts relapse of DLBCL in the CNS also when CNS-IPI is taken into account.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
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
结局指标
主要结局
CSF tumor cfDNA and metabolite detectability and cytological/flow cytometric confirmation of CNS lymphoma at the time of diagnosis and relapse
时间窗: Two years
次要结局
- Comparison of tumor cfDNA and metabolite levels and composition in CSF with levels in plasma at the time of diagnosis and relapse(Two years)
- Progression free survival, PFS (time between inclusion and progression or relapse or beginning of a new treatment)(Two years)
- Overall survival, OS (time between inclusion and death)(Two years)
- YKL-40 in CSF as biomarker of CNS lymphoma(Two years)
- Correlation of tumor cfDNA and/or metabolite identification in CSF of patients prior to diagnosis of CNS lymphoma at the time of diagnosis and relapse versus the appearance of later CNS lymphoma involvement(Two years)
- Comparison of mutational profile in diagnostic biopsy and/or cfDNA in peripheral blood with cfDNA in CSF and comparison of metabolic profiles in blood versus CSF in patients with and without development of CNS relapse.(Two years)
- Comparison of CSF cytokines, other biomarkers and tumor DNA and metabolic profile in the prediction of CNS lymphoma disease(Two years)
- For patients with both a pre- and a post-treatment CSF sample: correlation of cfDNA/metabolite levels pre-treatment to post-treatment with OS and risk of relapse.(Two years)
- Correlation of tumor cfDNA and metabolite levels and composition in CSF and patient survival at the time of diagnosis and relapse(Two years)
- Comparison of the clonal similarity between tumor DNA in the blood and the CSF at relapse versus tumor DNA in the primary tumor (by NGS panel sequencing)(Two years)
研究者
Lars Møller Pedersen
Senior consultant
Herlev Hospital