Diffuse Large B Cell LymphomaCNSctDNANCT04112238
ctDNA and Metabolites in CSF as Early Biomarkers of Secondary CNS Involvement in Diffuse Large B-cell Lymphoma
An observational study of Diffuse Large B Cell Lymphoma and Central Nervous System Metastasis, run by Herlev Hospital at 1 site in Denmark.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diffuse Large B Cell Lymphoma, Central Nervous System Metastasis
- How many people
- 75 participants
- Where
- 1 siteDenmark
- Study dates
- 29 Aug 2019to 1 Jun 2023
- How long will I take part?
- 2 Years
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: See above
Who may be able to join
- Verified or suspected primary CNS lymphoma or verified or suspected DLBCL relapsed in the CNS
- Treatment of the relapse not initiated (except pretreatment with corticosteroids)
- Age ≥ 18 years
- Patient must consent to genetic and metabolomic analysis of their cancer
- Written informed consent
- Previously diagnosed histologically documented DLBCL
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- Verified relapsed DLBCL
- ≥ 1 prior DLBCL treatments
- Treatment of the relapse not initiated (except pretreatment with corticosteroids)
- Being able to undergo standard assessment ( eg, Fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG-PET), MRI of the neuroaxis and bone marrow biopsy)
- Tumor biopsy and/or bone-marrow biopsy used for diagnosis available
- Age ≥ 18 years
- ECOG performance status of 0, 1 or 2
- Life expectancy ≥ 12 weeks
- Patient must consent to permit genetic and metabolomic analysis of their cancer
- Patient must consent to permit access to records in order to ascertain progression or relapse of their cancer
- Written informed consent
- A newly diagnosed and histologically verified DLBCL
- No prior DLBCL treatments
- Anti-lymphoma treatment not initiated (except pretreatment with corticosteroids)
- CNS-IPI >/= 3
- Being able to undergo standard assessment ( eg, Fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG-PET), MRI of the neuroaxis and bone marrow biopsy)
- Tumor biopsy and/or bone-marrow biopsy used for diagnosis available
- Age ≥ 18 years
- ECOG performance status of 0, 1 or 2
- Life expectancy >/= 12 weeks
- Patient must consent to permit genetic analysis of their cancer
- Patient must consent to permit access to records in order to ascertain progression or relapse of their cancer
- Written informed consent
Who cannot join
- Evidence of a CNS mass creating mass-effect or midline shift such that lumbar puncture is contraindicated
- Other contraindications to lumbar puncture according to local guidelines
- Other previous or current hematological malignancy
- Prior treatment for CNS disease (except CNS prophylaxis in first line lymphoma treatment)
- Known CNS autoimmune or inflammatory disease
- Known HIV infection
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- Patient is currently receiving treatment for DLBCL
- Study 1
- Evidence of a CNS mass creating mass-effect or midline shift such that lumbar puncture is contraindicated
- Other contraindications to lumbar puncture according to local guidelines
- Other previous or current hematological malignancy
- Previous or current primary CNS malignancy including know DLBCL relapse to the CNS
- Prior treatment for CNS disease (except CNS prophylaxis in first line lymphoma treatment)
- Known CNS autoimmune or inflammatory disease
- Known HIV infection
- Patient is currently receiving treatment for DLBCL (except pretreatment with corticosteroids)
- Study 2
- Evidence of a CNS mass creating mass-effect or midline shift such that lumbar puncture is contraindicated
- Other contraindications to lumbar puncture according to local guidelines
- Other previous or current hematological malignancy
- Previous or current primary CNS malignancy including primary CNS lymphoma
- Prior treatment for CNS disease
- Known CNS autoimmune or inflammatory disease
- Known HIV infection
- Patient is currently receiving treatment for DLBCL (except pretreatment with corticosteroids)
Trial locations and contacts
1 site in 1 country.
Denmark1 site, 1 recruiting
- Recruiting
Herlev Hopital
Herlev, Capital Region, 2730
Anne Elisabeth Reuben Tolley, MD, +4538686877, anne.elisabeth.reuben.tolley@regionh.dk
Lars Møller Pedersen, MD, PhD, +4568686527, lars.moeller.pedersen.01@regionh.dk
About this study
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
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.
Read the detailed description
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.
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse
What is being measured
The primary outcome is the main question the study is designed to answer.
CSF tumor cfDNA and metabolite detectability and cytological/flow cytometric confirmation of CNS lymphoma at the time of diagnosis and relapse
Measured: Two years
Secondary outcomes (10)
Progression free survival, PFS (time between inclusion and progression or relapse or beginning of a new treatment)
Measured: Two years
Overall survival, OS (time between inclusion and death)
Measured: Two years
Comparison of tumor cfDNA and metabolite levels and composition in CSF with levels in plasma at the time of diagnosis and relapse
Measured: 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.
Measured: Two years
Correlation of tumor cfDNA and metabolite levels and composition in CSF and patient survival at the time of diagnosis and relapse
Measured: 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
Measured: 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)
Measured: Two years
Comparison of CSF cytokines, other biomarkers and tumor DNA and metabolic profile in the prediction of CNS lymphoma disease
Measured: 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.
Measured: Two years
YKL-40 in CSF as biomarker of CNS lymphoma
Measured: Two years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2019
- Study start29 Aug 2019
- Primary completion1 Jun 2023 (estimated)
- Study completion1 Jun 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diffuse Large B Cell LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 75 participants (estimated)
- Target duration
- 2 Years
Sponsor and investigators
- Lead sponsor
- Herlev Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Weill Medical College of Cornell University
- Responsible party
- Principal investigator, Lars Møller Pedersen, Herlev Hospital
- Investigators
- Anne Elisabeth Reuben Tolley, MD, Principal investigator, Herlev Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04112238
- Sponsor's protocol ID
- CNSctDNA
- Acronym
- CNSctDNA
- Status last verified
- Mar 2022
- First submitted
- 30 Sep 2019
- Last updated
- 22 Mar 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04112238
- Acronym / sponsor ID
- CNSctDNA / CNSctDNA
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 75 participants (estimated)
- Lead sponsor
- Herlev HospitalUniversity, hospital or other
- Collaborators
- Weill Medical College of Cornell University
- Study start
- 29 Aug 2019 (actual)
- Primary completion
- 1 Jun 2023 (estimated)
- Study completion
- 1 Jun 2023 (estimated)
- First posted
- 2 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 design
- Observational model
- Case only
- Time perspective
- Prospective
- Target follow-up
- 2 Years
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- See above
Key inclusion criteria (29 listed)
- Verified or suspected primary CNS lymphoma or verified or suspected DLBCL relapsed in the CNS
- Treatment of the relapse not initiated (except pretreatment with corticosteroids)
- Age ≥ 18 years
- Patient must consent to genetic and metabolomic analysis of their cancer
- Written informed consent
Key exclusion criteria (25 listed)
- Evidence of a CNS mass creating mass-effect or midline shift such that lumbar puncture is contraindicated
- Other contraindications to lumbar puncture according to local guidelines
- Other previous or current hematological malignancy
- Prior treatment for CNS disease (except CNS prophylaxis in first line lymphoma treatment)
- Known CNS autoimmune or inflammatory disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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
10 secondary outcomes
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anne Elisabeth Reuben Tolley, MD principal investigator
Herlev Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Diffuse Large B Cell Lymphoma and Central Nervous System Metastasis, run by Herlev Hospital at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 29 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Anne Elisabeth Reuben Tolley, MD (+4538686877, anne.elisabeth.reuben.tolley@regionh.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Mar 2022.