ctDNA and Metabolites in CSF as Early Biomarkers of Secondary CNS Involvement in Diffuse Large B-cell Lymphoma (CNSctDNA)
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|ClinicalTrials.gov Identifier: NCT04112238|
Recruitment Status : Recruiting
First Posted : October 2, 2019
Last Update Posted : October 4, 2019
|Condition or disease|
|Diffuse Large B Cell Lymphoma Central Nervous System Metastasis|
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.
Hypothesis 4: Particular aberrations of cfDNA and/or metabolite profiles detected in blood (plasma) may, in some cases, be associated with CNS involvement in DLBCL patients and/or predict CNS relapse.
The study is composed of a pilot study including 5 patients with verified either primary or secondary CNS lymphoma followed by two studies: One including 40 patients with de novo DLBCL and one including 30 patients in a relapse setting. The patients will have to consent to having a lumbar puncture performed and blood samples taken before treatment initiation. After treatment a second set of lumbar puncture and blood samples will be requested.
|Study Type :||Observational [Patient Registry]|
|Estimated Enrollment :||75 participants|
|Target Follow-Up Duration:||2 Years|
|Official Title:||Circulating Cell-free Tumor DNA and Metabolites in Cerebrospinal Fluid as Early Biomarkers of Secondary CNS Involvement in Diffuse Large B-cell Lymphoma|
|Actual Study Start Date :||August 29, 2019|
|Estimated Primary Completion Date :||June 2023|
|Estimated Study Completion Date :||June 2023|
- CSF tumor cfDNA and metabolite detectability and cytological/flow cytometric confirmation of CNS lymphoma at the time of diagnosis and relapse [ Time Frame: Two years ]
- Progression free survival, PFS (time between inclusion and progression or relapse or beginning of a new treatment) [ Time Frame: Two years ]
- Overall survival, OS (time between inclusion and death) [ Time Frame: Two years ]
- Comparison of tumor cfDNA and metabolite levels and composition in CSF with levels in plasma at the time of diagnosis and relapse [ Time Frame: 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. [ Time Frame: Two years ]
- Correlation of tumor cfDNA and metabolite levels and composition in CSF and patient survival at the time of diagnosis and relapse [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: Two years ]
- Comparison of CSF cytokines, other biomarkers and tumor DNA and metabolic profile in the prediction of CNS lymphoma disease [ Time Frame: 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. [ Time Frame: Two years ]
- YKL-40 in CSF as biomarker of CNS lymphoma [ Time Frame: Two years ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04112238
|Contact: Anne Elisabeth Reuben Tolley, MDfirstname.lastname@example.org|
|Contact: Lars Møller Pedersen, MD, PhD||+4538686527||lars.moeller.pedersen.1.@regionh.dk|
|Principal Investigator:||Anne Elisabeth Reuben Tolley, MD||Herlev Hospital|