cfDNA Testing for Follicular Lymphoma

Recruiting at 8 trial locations

Overseen By Paola Ghione, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Second-line therapy, others

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

Compensation: Varies

Number of Visits: 11

Duration: 6-8 cycles

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how cell-free DNA (cfDNA), present in the blood, can predict the response of individuals with follicular lymphoma to their initial treatment. Researchers aim to determine if changes in cfDNA levels correlate with treatment success and if genetic variations in the cancer influence these outcomes. The study involves two groups: one with newly diagnosed individuals about to begin treatment, and another with those in long-term remission. This trial suits individuals with confirmed follicular lymphoma who have not started their second treatment or have been in remission for over ten years. As a Phase 1 trial, the research focuses on understanding the treatment's effects in people, offering participants the opportunity to contribute to groundbreaking insights.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It focuses on measuring cfDNA in relation to the usual first-line treatment for follicular lymphoma.

What prior data suggests that cfDNA testing is safe for follicular lymphoma patients?

Research has shown that cell-free DNA (cfDNA) testing helps monitor diseases like follicular lymphoma by examining small pieces of DNA in the blood. This testing is usually easy for patients because it mainly involves taking a blood sample. Studies have found that cfDNA testing can indicate how well a patient's lymphoma treatment is working.

In this trial, cfDNA testing serves as a method to collect information about the disease, not as a drug or treatment. Therefore, the cfDNA testing process itself poses no direct safety concerns. It is simply a blood test, which is a common and low-risk procedure. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about cfDNA testing for follicular lymphoma because it offers a non-invasive way to monitor the disease. Unlike traditional methods that rely heavily on imaging and can be invasive, cfDNA testing involves a simple blood draw to detect cancer DNA fragments in the bloodstream. This method could potentially catch recurrences or responses to treatment earlier than current options, allowing for a more personalized approach to managing the disease. Additionally, by using cfDNA testing in both newly diagnosed and long-term remission patients, researchers hope to gain insights into the dynamics of the disease and improve outcomes.

What evidence suggests that cfDNA testing is effective for follicular lymphoma?

Research has shown that cfDNA testing can effectively monitor and predict treatment efficacy for follicular lymphoma. It proves more reliable than other methods for detecting the disease in lymphomas. In this trial, participants in the retrospective group, who have received first-line treatment and are in complete remission, will have blood collected for cfDNA testing to study long-term remissions. Meanwhile, participants in the prospective group, with untreated, newly diagnosed follicular lymphoma, will have blood collected for cfDNA testing before, during, and after their first-line treatment or observation period. Some studies found that cfDNA could predict a patient's response to treatment and the potential for early disease recurrence. Additionally, cfDNA testing is highly sensitive, detecting tiny amounts of tumor DNA in the blood. This sensitivity makes it a valuable tool for assessing treatment effectiveness and identifying changes early. ^{1 6 7 8 9}

Who Is on the Research Team?

Paola Ghione, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with confirmed grade 1-3a follicular lymphoma who can follow the study schedule and requirements. They must have measurable disease that shows up on scans and either have enough tissue from previous biopsies or are planning a biopsy. People already receiving second-line therapy cannot join, except those in long-term survival after first-line treatment.

Inclusion Criteria

Ability to adhere to the study visit schedule and all the protocol requirements

Measurable FDG-avid disease

I have enough stored tissue for testing or will have a biopsy to provide it.

Exclusion Criteria

I am receiving my second or later treatment for my condition, except if I've survived follicular lymphoma for over 10 years since my first treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive first-line treatment for follicular lymphoma, with cfDNA levels measured before, during, and after treatment

6-8 cycles

Visits at the start, after 2 cycles, and at the completion of 6-8 cycles

Follow-up

Participants are monitored for cfDNA levels every 6 months for a total of 2 years from the initiation of therapy

2 years

Every 6 months

Radiation Therapy Follow-up

For patients receiving RT, cfDNA levels are measured before RT and at 3, 6, 12, 18, and 24 months post RT

24 months

Visits at 3, 6, 12, 18, and 24 months post RT

What Are the Treatments Tested in This Trial?

Interventions

• cfDNA

Trial Overview The study measures cell-free DNA (cfDNA) levels in blood at different times during standard first-line treatment for follicular lymphoma to see if cfDNA relates to how well patients respond. It also examines genetic changes in the cancer cells and their impact on treatment response.

How Is the Trial Designed?

Group I: Retrospective Group Experimental Treatment 4 Interventions

Study participants who have received first-line treatment for follicular lymphoma and are in complete remission will have blood collected for cfDNA testing. In the retrospective cohort, MSKCC patients with CRs lasting ≥10 years after induction therapy will be studied. Initial tumor tissue (if available) will be collected to examine the status of s cfDNA in patients with long-term remissions. Blood samples will be collected once, if the patient has interesting results (e.g. positive cfDNA sample despite CR on imaging, etc.) then additional blood samples may be taken during follow up visits.

Group II: Prospective Group Experimental Treatment 4 Interventions

Study participants with untreated, newly diagnosed follicular lymphoma will have blood collected for cfDNA testing before, during, and after their first-line treatment or observation period

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

This study evaluated 20 treatment-naive follicular lymphoma (FL) patients and found that higher concentrations of circulating cell-free DNA (cfDNA) and specific somatic mutations in cfDNA were associated with poorer survival outcomes, indicating cfDNA's potential as a prognostic tool.

The presence of BCL2 mutations in cfDNA improved the ability to predict patient outcomes and could guide targeted therapies, suggesting that cfDNA analysis may enhance diagnosis and risk stratification in FL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plasma Concentrations and Cancer-Associated Mutations in Cell-Free Circulating DNA of Treatment-Naive Follicular Lymphoma for Improved Non-Invasive Diagnosis and Prognosis. Hatipoğlu, T., Esmeray Sönmez, E., Hu, X., et al.[2022]

Circulating cell-free DNA (cfDNA) testing is a promising minimally invasive method for managing metastatic non-small-cell lung cancer (NSCLC), offering insights into tumor heterogeneity and allowing for repeated assessments over time.

cfDNA testing can be used for various applications, including early diagnosis, monitoring treatment response, and identifying predictive markers, highlighting its potential to enhance patient management in NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of circulating free DNA in the management of NSCLC. Esposito Abate, R., Pasquale, R., Fenizia, F., et al.[2019]

Many women who received high-risk, false positive, or inconclusive results from cell-free DNA (cfDNA) screening reported feeling misled by the information provided before testing, leading to significant decisional regret about their choice to undergo screening.

One third of the participants indicated they would not choose cfDNA screening in future pregnancies, highlighting the need for improved communication and understanding of the screening's accuracy and potential outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decisional regret in women receiving high risk or inconclusive prenatal cell-free DNA screening results. Gammon, BL., Jaramillo, C., Riggan, KA., et al.[2023]

Circulating cell-free DNA (CFDNA) levels are significantly higher in lymphoma patients compared to those with lymphadenitis and healthy individuals, suggesting that CFDNA quantification could be a valuable screening tool for lymphoma.

A higher clearance rate of circulating CFDNA after standard therapy is associated with better treatment outcomes, including higher complete remission rates and longer overall survival, indicating its potential as a prognostic indicator.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Quantitation of Circulating Cell-free DNA in Patients with Lymphoma and Its Clinical Significance]. Chen, YY., Guo, SQ., Li, YH., et al.[2018]

Standardizing the pre-analytical processes for cell-free DNA (cfDNA) testing is crucial for obtaining reliable results, especially due to the low amounts and stability of circulating tumor DNA (ctDNA).

The review provides evidence-based guidelines for pre-analytical procedures specifically for plasma EGFR variant testing, suggesting that these standardized practices can enhance the accuracy and effectiveness of cfDNA testing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Practice Guidelines for Pre-Analytical Procedures of Plasma Epidermal Growth Factor Receptor Variant Testing. Shin, S., Woo, HI., Kim, JW., et al.[2022]

Cell-free DNA (cfDNA) analysis, or liquid biopsy, is a promising noninvasive method for monitoring minimal residual disease in lymphomas, offering advantages like ease of blood sample collection and rapid results.

This technique allows for real-time monitoring of treatment responses and can quickly detect treatment resistance, making it a significant advancement in the management of lymphoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cell-free DNA and the monitoring of lymphoma treatment. Camus, V., Jardin, F.[2020]

Next-generation sequencing (NGS) is enhancing our understanding of the genetic diversity in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL), which could lead to better classification and treatment strategies for these cancers.

Molecular testing can help identify patients who may benefit from targeted therapies and predict treatment outcomes, potentially improving patient management and outcomes for those with relapsed or refractory lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integration of molecular testing for the personalized management of patients with diffuse large B-cell lymphoma and follicular lymphoma. Stuckey, R., Luzardo Henríquez, H., de la Nuez Melian, H., et al.[2023]

A study of 50 lymphoma patients using next-generation sequencing (NGS) on circulating cell-free DNA (cfDNA) revealed a median of 64 genetic variants per sample, highlighting the genetic diversity among different lymphoma subtypes.

The concentration of cfDNA was significantly correlated with clinical indices in diffuse large B cell lymphoma (DLBCL), suggesting that cfDNA analysis could be useful for understanding disease progression and tailoring treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mutation Profiling of Malignant Lymphoma by Next-Generation Sequencing of Circulating Cell-Free DNA. Sun, P., Chen, C., Xia, Y., et al.[2020]

In a study of 28 patients with newly diagnosed follicular lymphoma, circulating tumor DNA (ctDNA) mutations were found in 75% of patients, indicating that ctDNA can be a useful biomarker for assessing tumor burden and prognosis.

Specific mutations in genes such as KMT2D, EP300, and STAT6 were linked to shorter progression-free survival (PFS), suggesting that these mutations could help identify patients at higher risk for disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Application of circulating tumour DNA in terms of prognosis prediction in Chinese follicular lymphoma patients. Zhao, M., Li, Q., Yang, J., et al.[2023]

In a study of 36 patients with follicular lymphoma, higher levels of circulating tumor DNA (ctDNA) before treatment were linked to a greater risk of early disease progression (POD24) and a lower chance of achieving complete response (CR).

Monitoring ctDNA levels during treatment can effectively predict patient responses and early progression, suggesting that ctDNA analysis could be a valuable tool for personalizing treatment strategies in follicular lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monitoring of Circulating Tumor DNA Predicts Response to Treatment and Early Progression in Follicular Lymphoma: Results of a Prospective Pilot Study. Fernández-Miranda, I., Pedrosa, L., Llanos, M., et al.[2023]

In a study of 143 patients with advanced non-small-cell lung cancer (NSCLC), circulating cell-free DNA (cfDNA) testing identified actionable mutations in 20% of samples at diagnosis, allowing for targeted therapy initiation in 10% of cases where tissue biopsies were not feasible.

cfDNA testing demonstrated a sensitivity of 67% and specificity of 89%, showing it can effectively guide treatment decisions and avoid invasive procedures, with a high response rate of 88% among patients who started targeted therapy based solely on cfDNA results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Non-Small-Cell Lung Cancer Based on Circulating Cell-Free DNA and Impact of Variation Allele Frequency. Bustamante Alvarez, JG., Janse, S., Owen, DH., et al.[2022]

A study of 101 laboratories revealed that most circulating tumor DNA (cfDNA) testing is conducted by commercial and international labs, which tend to have higher test volumes and larger gene panels compared to hospital-based labs.

The findings indicate that while both next-generation sequencing (NGS) and non-NGS methods are used to analyze key cancer-related genes, laboratories using FDA-approved non-NGS assays for EGFR show higher analytical sensitivities, suggesting a potential advantage in accuracy for specific tests.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Testing for Tumor Cell-Free DNA: College of American Pathologists Proficiency Programs Reveal Practice Trends. Devereaux, KA., Souers, RJ., Merker, JD., et al.[2023]

Cell-free DNA (cfDNA) testing is a promising noninvasive method for detecting classical Hodgkin lymphoma (cHL), offering advantages like ease of blood sample collection, quick results, and consistency with tumor DNA analysis.

cfDNA levels correlate with important clinical features and can be used to evaluate treatment responses and monitor minimal residual disease, making it a valuable tool alongside traditional imaging methods like PET.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cell-Free DNA for the Management of Classical Hodgkin Lymphoma. Camus, V., Jardin, F.[2021]

Cell-free DNA (cfDNA) levels in plasma are significantly higher in lymphoma patients at initial diagnosis compared to those in the treated stage, and also higher than in healthy controls, indicating its potential as a biomarker for lymphoma.

cfDNA concentration correlates with important clinical parameters such as ECOG score and LDH levels, and shows better sensitivity and specificity for diagnosing lymphoma compared to traditional LDH testing, suggesting it could be a valuable tool for monitoring treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The analysis of cell-free DNA concentrations and integrity in serum of initial and treated of lymphoma patients. Wu, J., Tang, W., Huang, L., et al.[2019]

Citations

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

Circulating tumor DNA in lymphoma: technologies and ... Analytical sensitivity, tested by diluting lymphoma ctDNA in healthy cfDNA, achieved a detection threshold of 0.00005% (Table 1) [108]. Other ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9245363/

Circulating Tumor DNA in Lymphoma: Principles and Future ... cfDNA is more reliable than circulating tumor cells for detection of disease in most lymphomas. Genotypic profiles in ctDNA strongly correlate with profiles in ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04468841

Measuring Cell-Free DNA (cfDNA) Levels in People With ... Study participants who have received first-line treatment for follicular lymphoma and are in complete remission will have blood collected for cfDNA testing.

4. aacrjournals.org aacrjournals.org/clincancerres/article/29/1/209/711966/Monitoring-of-Circulating-Tumor-DNA-Predicts

Monitoring of Circulating Tumor DNA Predicts Response to ... Monitoring of circulating tumor DNA predicts response to treatment and early progression in follicular lymphoma: results of a prospective pilot study.

5. ashpublications.org ashpublications.org/bloodadvances/article/2/7/807/15817/Total-metabolic-tumor-volume-circulating-tumor

Total metabolic tumor volume, circulating tumor cells, cell-free ... TMTV was a better predictor of poor outcome with a 4-year estimate of 59% in patients with TMTV >510 cm3, whereas cfDNA was a better predictor ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5060014/

Circulating cell-free DNA in hematological malignancies Detectable interim circulating tumor DNA had a positive predictive value of 62·5% (95% CI 40·6–81·2) and a negative predictive value of 79·8% (69·6–87·8), ...

7. nature.com nature.com/articles/s41408-025-01322-9

Incidental vs. symptomatic diagnosis of follicular lymphoma Incidental detection of FL is associated with earlier stages and more favorable disease characteristics. However, this did not translate into improved survival ...

8. tandfonline.com tandfonline.com/doi/full/10.1080/14737159.2025.2500659

Circulating tumor DNA as a powerful tool in diagnostics ... Our review provides a comprehensive overview and summary of available ctDNA studies in LBCL and FL. The accuracy of ctDNA-based detection of lymphoma-associated ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11146396/

Dynamic monitoring of circulating tumor DNA reveals ... Patients with undetectable ctDNA negative (ctDNA–) at day 14 (D14) achieved an impressive 3-month complete response rate of 77.8% vs 22.2% (p= ...