ctDNA Testing for B-Cell Lymphoma

Recruiting at 6 trial locations

Overseen By Ariela Noy, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Active malignancy, Uncontrolled illness, Active infection, Psychiatric illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: up to 2 years

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new testing method called cerebral spinal fluid (CSF) ctDNA testing to predict the risk of central nervous system (CNS) relapse in people with B-cell lymphoma. Researchers aim to determine how many high-risk individuals test positive for ctDNA in their CSF despite showing no CNS involvement with standard tests. The study tracks the frequency of CNS relapse in these patients. Ideal participants are those diagnosed with certain high-risk types of B-cell lymphoma who have not yet started treatment for an aggressive form of the disease. As a Phase 2 trial, this research focuses on assessing the effectiveness of the testing method in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, systemic corticosteroids are allowed if they are used for 7 days or less and reduced to a low dose by the start of treatment. It's best to discuss your specific medications with the trial team.

What prior data suggests that Cerebral Spinal Fluid ctDNA Testing is safe for participants with B-cell lymphoma?

Research shows that testing for circulating tumor DNA (ctDNA) in the cerebrospinal fluid (CSF) is becoming a popular method for studying B-cell lymphomas. This process involves detecting tiny pieces of tumor DNA in the fluid surrounding the brain and spine. Studies have shown that this method is usually non-invasive, making it less risky and easier on the body compared to procedures like biopsies.

Past research has demonstrated that ctDNA testing provides a safe way to learn about lymphoma without causing major side effects. Most patients tolerate the procedure well. It typically involves taking a small sample of CSF, which is generally safe, though it might cause temporary discomfort such as headaches.

Since this trial is in an early phase, the safety of the treatment is still under investigation. However, using ctDNA testing in other contexts has not shown major safety concerns. This is reassuring, but it is important to remember that individual experiences can differ. Always discuss potential risks with the study team before joining. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Cerebral spinal fluid (CSF) ctDNA testing for B-cell lymphoma is unique because it offers a non-invasive way to monitor cancer activity and potential relapse in the central nervous system (CNS). Most treatments for diffuse large B-cell lymphoma (DLBCL) involve chemotherapy and immunotherapy, focusing on directly attacking cancer cells. However, CSF ctDNA testing doesn't treat the cancer itself but instead provides valuable insights by detecting tiny fragments of tumor DNA in the spinal fluid, which can signal early relapse risk. This early detection could lead to more timely and targeted interventions, potentially improving outcomes for high-risk patients. Researchers are excited because it represents a shift towards more personalized and proactive cancer management.

What evidence suggests that cerebral spinal fluid ctDNA testing is effective for detecting CNS relapse in B-cell lymphoma?

Research has shown that testing for small pieces of tumor DNA in the fluid around the brain and spine holds promise for detecting genetic changes in brain cancer. In this trial, participants with B-cell lymphoma will undergo Cerebral Spinal Fluid ctDNA Testing, which can identify changes that regular tests might miss. Studies have found that testing DNA from spinal fluid provides a good, less invasive method to monitor lymphoma. This testing helps assess the risk of cancer spreading to the brain and spine. By revealing genetic patterns, this DNA testing might enhance doctors' ability to predict and manage cancer recurrence in the brain and spine. ^{3 6 7 8 9}

Who Is on the Research Team?

Jennifer Lue, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with various types of B-cell lymphoma who are at high risk for CNS relapse. It's designed to detect the presence of tumor DNA in their spinal fluid, even when standard tests show no signs of CNS involvement.

Inclusion Criteria

Signed Informed Consent

I am scheduled for standard chemoimmunotherapy.

Ability and willingness to comply with the requirements of the study protocol

Exclusion Criteria

I do not have an active infection or major infection in the last 2 weeks.

I haven't had treatment for another cancer within the last 2 years, except for a slow-growing B-cell lymphoma.

I do not have any other active cancers.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive front line therapy for aggressive B-cell lymphoma and are monitored for CNS relapse risk

up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on CNS relapse

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Cerebral Spinal Fluid ctDNA Testing

Trial Overview The study focuses on testing cerebral spinal fluid (CSF) for circulating tumor DNA (ctDNA) in patients with B-cell lymphoma. It aims to determine how ctDNA correlates with the risk and occurrence of central nervous system (CNS) relapse.

How Is the Trial Designed?

Group I: Participants with Diffuse large B-cell lymphoma (DLBCL) i Experimental Treatment 1 Intervention

Participants will be deemed clinically high-risk for CNS relapse. Participants will be considered to be high-risk for CNS relapse as determined by CNS-IPI score, pathological characteristics such as the presence of MYC, BCL2 and/or BCL6 translocations and specific extranodal involvement such as breast, renal, adrenal, nasopharyngeal, epidural/paraspinal involvement

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

Circulating tumor DNA (ctDNA) liquid biopsies offer a promising method to obtain crucial molecular information about large B-cell lymphomas (LBCLs), which are known for their clinical and biological diversity.

ctDNA can aid in mutational genotyping, molecular classification, and detecting minimal residual disease, potentially improving the application of molecular features in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cell-free DNA in large B-cell lymphoma: MRD and beyond. Sworder, BJ., Kurtz, DM.[2023]

Liquid biopsy of cerebrospinal fluid (CSF) offers a minimally invasive method to detect genetic alterations in tumors, allowing for better diagnosis and monitoring of central nervous system malignancies.

The analysis of circulating tumor DNA (ctDNA) from CSF can facilitate initial molecular characterization and ongoing treatment adjustments, potentially leading to improved cancer care as technologies advance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebrospinal fluid: A unique source of circulating tumor DNA with broad clinical applications. Hickman, RA., Miller, AM., Arcila, ME.[2023]

Circulating tumor DNA (ctDNA) is a promising minimally invasive method for detecting and monitoring various lymphoma subtypes, providing critical information on genotyping, treatment response, and predicting relapse.

ctDNA can detect minimal residual disease even when traditional imaging shows no signs of cancer, highlighting its potential as a powerful biomarker for improving diagnosis and treatment outcomes in lymphoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circulating Tumor DNA in Lymphoma. Thiruvengadam, SK., Zain, J.[2023]

A predictive model was developed to improve the detection rate of circulating tumor DNA (ctDNA) in cerebrospinal fluid (CSF) from non-small-cell lung cancer (NSCLC) patients with brain metastases, achieving an accuracy of 80% in a training cohort of 66 patients.

The model identified key imaging characteristics, such as the size of the largest brain lesion and its distance to the ventricle, which significantly enhanced the detection rate of ctDNA from 58.18% to 81.81% in a validation cohort, indicating its potential to optimize clinical utility of CSF liquid biopsies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utilizing phenotypic characteristics of metastatic brain tumors to improve the probability of detecting circulating tumor DNA from cerebrospinal fluid in non-small-cell lung cancer patients: development and validation of a prediction model in a prospective cohort study. Li, M., Hou, X., Zheng, L., et al.[2022]

Circulating tumor DNA (ctDNA) detection through simple blood draws or lumbar punctures offers a non-invasive method to monitor CNS lymphomas, which are difficult to sample through traditional means.

Profiling ctDNA can provide real-time insights into the genetic makeup of CNS lymphomas, aiding in risk stratification, outcome prediction, and personalized treatment decisions, potentially improving patient management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical applications of circulating tumor DNA in central nervous system lymphoma. Foerster, AK., Lauer, EM., Scherer, F.[2023]

Circulating tumor DNA (ctDNA) assessment has shown promise in diagnosing and monitoring various lymphoma subtypes, including diffuse large B-cell lymphoma and Hodgkin lymphoma, indicating its potential as a valuable tool in lymphoma management.

Recent advances in ctDNA applications include developing new prognostic models and assessing treatment response, suggesting that ctDNA could enhance personalized medicine approaches in lymphoma, although further studies are needed for clinical validation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updates on Circulating Tumor DNA Assessment in Lymphoma. Darrah, JM., Herrera, AF.[2019]

In a study of 19 patients with various types of lymphomas, circulating tumor DNA (ctDNA) levels in cerebrospinal fluid (CSF) were found to be more effective at detecting central nervous system (CNS) lesions compared to plasma ctDNA, especially in patients with restricted CNS lymphoma.

CSF ctDNA was able to predict CNS relapse earlier than conventional methods, as it was detected in patients months before clinical relapse was confirmed, and it also identified residual disease more accurately than flow cytometry after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cell free circulating tumor DNA in cerebrospinal fluid detects and monitors central nervous system involvement of B-cell lymphomas. Bobillo, S., Crespo, M., Escudero, L., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT06736613

NCT06736613 | A Study of Circulating Tumor DNA (ctDNA) ... The purpose of this study is to find out how many people with B-cell lymphoma who are at high risk for central nervous system/CNS relapse test positive for ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8122255/

ctDNA-Based Liquid Biopsy of Cerebrospinal Fluid in Brain ... The analysis of the cell-free circulating tumour DNA can reveal the genetic profile of brain cancer in a relatively noninvasive manner.

3. sciencedirect.com sciencedirect.com/science/article/pii/S0046817724001886

Clinical use of circulating tumor DNA analysis in patients ... The analysis of circulating tumor DNA (ctDNA) in liquid biopsy specimens has an established role for the detection of predictive molecular alterations.

4. nature.com nature.com/articles/s41375-022-01618-w

Circulating tumor DNA in B-cell lymphoma In lymphoma, ctDNA obtained from blood plasma or cerebrospinal fluid has been studied as a non- or minimal-invasive clinical biomarker. At the ...

5. jhoonline.biomedcentral.com jhoonline.biomedcentral.com/articles/10.1186/s13045-025-01673-7

Circulating tumor DNA in lymphoma: technologies and ... This review comprehensively summarizes common genetic variations in lymphoma and systematically evaluates ctDNA detection technologies, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9417989/

Circulating tumor DNA in B-cell lymphoma - PubMed Central Circulating tumor DNA (ctDNA) in the blood plasma or CSF has become the most investigated analyte in B-cell lymphomas, as the majority of lymphoma patients do ...

7. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/562715

A Study of Circulating Tumor DNA (ctDNA) Testing for ... The purpose of this study is to find out how many people with B-cell lymphoma who are at high risk for central nervous system/CNS relapse ...

8. ashpublications.org ashpublications.org/blood/article/144/10/1093/516189/Rapid-tumor-DNA-analysis-of-cerebrospinal-fluid

Rapid tumor DNA analysis of cerebrospinal fluid accelerates ... Rapid tumor DNA analysis of cerebrospinal fluid accelerates treatment of central nervous system lymphoma.

9. sciencedirect.com sciencedirect.com/science/article/pii/S1936523323000748

Cerebrospinal fluid: A unique source of circulating tumor ... This review outlines some of the key aspects of ctDNA from CSF as a highly suitable approach for clinical assessment, the benefits and drawbacks, testing ...