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

Trial Summary

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 data supports the effectiveness of the treatment Cerebral Spinal Fluid ctDNA Testing for B-Cell Lymphoma?

Research shows that ctDNA testing in cerebrospinal fluid (CSF) can detect central nervous system (CNS) lesions more effectively than other methods and can predict CNS relapse earlier than conventional techniques. This suggests that CSF ctDNA testing is a promising tool for monitoring and managing B-cell lymphomas with CNS involvement. ^{1 2 3 4 5}

Is ctDNA testing safe for humans?

ctDNA testing, including its use in cerebrospinal fluid (CSF), is generally considered safe as it involves minimal invasiveness, such as a simple blood draw or lumbar puncture, and does not require surgery. It has been used in various conditions, including central nervous system lymphomas, without specific safety concerns reported in the studies. ^{1 2 3 4 5}

How is ctDNA testing unique for treating B-cell lymphoma?

ctDNA testing for B-cell lymphoma is unique because it uses a simple blood test to detect tumor DNA, allowing for less invasive monitoring of the disease. This method can provide real-time information about the genetic makeup of the lymphoma, helping to predict treatment response and detect relapses earlier than traditional methods. ^{1 4 5 6 7}

What is the purpose of this trial?

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 cerebral spinal fluid/CSF ctDNA but test negative for CNS involvement using standard tests. The study will also look at how often CNS relapse happens in people with and without detected CSF ctDNA.

Research Team

Jennifer Lue, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. Italy pubmed.ncbi.nlm.nih.gov

Cell free circulating tumor DNA in cerebrospinal fluid detects and monitors central nervous system involvement of B-cell lymphomas. [2021]

2. England 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. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Cerebrospinal fluid: A unique source of circulating tumor DNA with broad clinical applications. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Circulating Tumor DNA in Lymphoma. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Clinical applications of circulating tumor DNA in central nervous system lymphoma. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Updates on Circulating Tumor DNA Assessment in Lymphoma. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Cell-free DNA in large B-cell lymphoma: MRD and beyond. [2023]