cfDNA Testing for Follicular Lymphoma
Recruiting in Palo Alto (17 mi)
+8 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Memorial Sloan Kettering Cancer Center
Disqualifiers: Second-line therapy, others
No Placebo Group
Trial Summary
What is the purpose of this trial?The researchers are doing this study to measure and test cell-free DNA (cfDNA) in the blood before, during, and after first-line treatment for follicular lymphoma. They will look at whether cfDNA levels are related to a person's response to the usual first-line treatment for follicular lymphoma. Researchers also want to understand how different genetic changes in follicular lymphoma relate to a person's response to the usual first-line treatment.
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 data supports the effectiveness of the treatment cfDNA for Follicular Lymphoma?
Research shows that analyzing cell-free DNA (cfDNA) can help in diagnosing and predicting the progression of follicular lymphoma by identifying specific genetic mutations linked to the disease. This method is non-invasive and can provide important information about the cancer's behavior, potentially guiding treatment decisions.
12345Is cfDNA testing safe for humans?
cfDNA testing is generally considered safe as it involves a noninvasive blood test, which is simple and has a fast turnover time. It has been used in various conditions, including lymphomas and prenatal screenings, without significant safety concerns reported.
678910How does cfDNA testing differ from other treatments for follicular lymphoma?
cfDNA testing for follicular lymphoma is unique because it uses a blood test to analyze DNA fragments from tumors, providing a non-invasive way to monitor the disease and predict treatment response, unlike traditional methods that rely on tissue biopsies.
311121314Eligibility Criteria
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
I am 18 or older and can give my consent, or someone legally allowed can on my behalf.
Ability to adhere to the study visit schedule and all the protocol requirements
Measurable FDG-avid disease
+2 more
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.
Trial Timeline
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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Group I: Retrospective GroupExperimental Treatment4 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 GroupExperimental Treatment4 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Memoral Sloan Kettering Basking Ridge (All Protocol Activities)Basking Ridge, NJ
Memoral Sloan Kettering Monmouth (All protocol activities)Middletown, NJ
Memorial Sloan Kettering Commack (All Protocol Activities)Commack, NY
Memorial Sloan Kettering Westchester (All Protocol Activities)Harrison, NY
More Trial Locations
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Who Is Running the Clinical Trial?
Memorial Sloan Kettering Cancer CenterLead Sponsor
References
Cell-free DNA and the monitoring of lymphoma treatment. [2020]The technique of cell-free DNA (cfDNA) analysis, also called liquid biopsy, has been developed over the past several years to serve as a minimal residual disease tool, as has already been done with reliability and robustness in acute leukemias. This technique has important theoretical advantages, including the simplicity of acquiring blood samples, which can easily be repeated over time, its noninvasive and quantitative nature, which provides results consistent with the results obtained from tumor genomic DNA, and its speed and low cost. cfDNA analysis, as the leading tool to quantify somatic mutations, is a major technological leap in the noninvasive management of lymphomas. This technology may empower monitoring and treatment adjustment in real time and enable the quick detection of refractory lymphomas and resistance to routine therapies. Here, we summarize the results that have established the clinical relevance of cfDNA in diagnostic and prognostic stratification and the monitoring of lymphoma treatments.
[Quantitation of Circulating Cell-free DNA in Patients with Lymphoma and Its Clinical Significance]. [2018]To evaluate the value of circulating cell-free DNA (CFDNA) quantification for screening lymphoma, to analyse the relationship of circulating CFDNA with curative effect under standard therapeutic schedule, and to determine whether circulating CFDNA could be applied to monitor and prognosticate lymphoma.
Plasma Concentrations and Cancer-Associated Mutations in Cell-Free Circulating DNA of Treatment-Naive Follicular Lymphoma for Improved Non-Invasive Diagnosis and Prognosis. [2022]Follicular lymphoma (FL) is the second most frequent non-Hodgkin lymphoma accounting for 10-20% of all lymphomas in western countries. As a clinically heterogeneous cancer, FL occasionally undergoes histological transformation to more aggressive B cell lymphoma types that are associated with poor prognosis. Here we evaluated the potential of circulating cell-free DNA (cfDNA) to improve the diagnosis and prognosis of follicular lymphoma patients. Twenty well-characterized FL cases (13 symptomatic and 7 asymptomatic) were prospectively included in this study. Plasma cfDNA, formalin-fixed paraffin-embedded (FFPE) tumor tissue DNA, and patient-matched granulocyte genomic DNA samples were obtained from 20 treatment-naive FL cases. Ultra-deep targeted next-generation sequencing was performed with these DNA samples by using a custom-designed platform including exons and exon-intron boundaries of 110 FL related genes. Using a strict computational bioinformatics pipeline, we identified 91 somatic variants in 31 genes in treatment-naive FL cases. Selected variants were cross-validated by using PCR-Sanger sequencing. We observed higher concentrations of cfDNA and a higher overlap of somatic variants present both in cfDNA and tumor tissue DNA in symptomatic FL cases compared to asymptomatic ones. Variants known to be associated with FL pathogenesis such as STAT6 p.D419 or EZH2 p.Y646 were observed in patient-matched cfDNA and tumor tissue samples. Consistent with previous observations, high Ki-67 staining, elevated LDH levels, FDG PET/CT positivity were associated with poor survival. High plasma cfDNA concentrations or the presence of BCL2 mutations in cfDNA showed significant association with poor survival in treatment-naive patients. BCL2 mutation evaluations in cfDNA improved the prognostic utility of previously established variables. In addition, we observed that a FL patient who had progressive disease contained histological transformation-associated gene (i.e. B2M and BTG1) mutations only in cfDNA. Pre-treatment concentrations and genotype of plasma cfDNA may be used as a liquid biopsy to improve diagnosis, risk stratification, and prediction of histological transformation. Targeted therapies related to oncogenic mutations may be applied based on cfDNA genotyping results. However, the results of this study need to be validated in a larger cohort of FL patients as the analyses conducted in this study have an exploratory nature.
Treatment of Non-Small-Cell Lung Cancer Based on Circulating Cell-Free DNA and Impact of Variation Allele Frequency. [2022]Next-generation sequencing of circulating cell-free DNA (cfDNA) can identify sensitizing and resistance mutations in non-small-cell lung cancer (NSCLC). cfDNA is helpful when tissue is insufficient for genomic testing or repeat biopsy is not feasible or poses unacceptable risk. Here we report the experience of cfDNA testing at the time of diagnosis and how this intervention can help avoid further invasive interventions, how it can be used to determine initiation of therapy, and how variation allele frequency of the somatic alteration affects response to subsequent treatment.
Clinical Testing for Tumor Cell-Free DNA: College of American Pathologists Proficiency Programs Reveal Practice Trends. [2023]Clinical testing for tumor cell-free DNA (cfDNA) has evolved rapidly, but no practice guidelines exist.
Mutation Profiling of Malignant Lymphoma by Next-Generation Sequencing of Circulating Cell-Free DNA. [2020]Background: Malignant lymphomas are a group of distinct lymphoid neoplasms, exhibiting marked diversity in biological behaviors and clinical outcomes. Liquid biopsy, such as circulating cell-free DNA (cfDNA), has recently been attempted to be used for mutation profiling of lymphomas using next-generation sequencing (NGS). However, only limited data about cfDNA are restricted in Hodgkin's lymphoma and B cell lymphoma, and there is no report in the T cell lymphoma so far. Patient and Methods: Medical records of a total of 50 lymphoma patients were retrospectively reviewed, and cfDNA samples were analyzed by capture-based NGS targeting 390 lymphoma- and cancer- relevant genes. We sought to explore the clinical utility of cfDNA in establishing the mutation profiles of different lymphoma subtypes and analyze the correlation between cfDNA concentration and other clinical indices such as serum LDH and IPI. Results: Somatic alterations were identified in cfDNA samples with a median of 64 variants per sample. The concentration of cfDNA in the plasma was found to be significantly correlated with the clinical indices in diffuse large B cell lymphoma (DLBCL). The genetic heterogeneity of different lymphoma subtypes was clearly observed in cfDNAs from germinal center B-cell (GCB) DLBCL, non-GCB DLBCL and natural killer/T-cell lymphoma (NKTCL), confirming that distinct molecular mechanisms are involved in the pathogenesis of different lymphomas. Conclusion: Our findings demonstrate that NGS-based cfDNA mutation profiling reveals genetic heterogeneity across lymphoma subtypes, with potential implications for the discovery of therapeutic targets, the exploration of genome evolution and the development of risk-adapted treatment.
Clinical Practice Guidelines for Pre-Analytical Procedures of Plasma Epidermal Growth Factor Receptor Variant Testing. [2022]Standardization of cell-free DNA (cfDNA) testing processes is necessary to obtain clinically reliable results. The pre-analytical phase of cfDNA testing greatly influences the results because of the low proportion and stability of circulating tumor DNA (ctDNA). In this review, we provide evidence-based clinical practice guidelines for pre-analytical phase procedures of plasma epidermal growth factor receptor gene (EGFR) variant testing. Specific recommendations for pre-analytical procedures were proposed based on evidence from the literature and our experimental data. Standardization of pre-analytical procedures can improve the analytical performance of cfDNA testing.
The analysis of cell-free DNA concentrations and integrity in serum of initial and treated of lymphoma patients. [2019]To evaluate cell-free DNA (cfDNA) in plasma as a promising biomarker for lymphoma, altered levels of cfDNA and its association with clinical parameters are investigated in patients suffered from lymphomas.
Decisional regret in women receiving high risk or inconclusive prenatal cell-free DNA screening results. [2023]Objectives: This study examined the experiences of women receiving high-risk cell-free DNA (cfDNA) screening results, with particular focus on decisional satisfaction after receiving high-risk, false, or inconclusive results. It is already known that cell-free DNA screening is rapidly expanding in the clinical practice. A growing number of women are offered cfDNA screening for an increasingly broad range of chromosomal and microdeletion syndromes. However, research shows that the very low false positive rate attributed to cfDNA screening for trisomy 21 does not apply to other conditions.Methods: As a part of the larger study on patient experiences, 40 semistructured telephone interviews were conducted with women who were, or had recently been, pregnant and received high-risk (n = 15), false positive/negative (n = 20), or inconclusive (n = 5) results from cfDNA screening.Results: One third of participants would not elect to have cfDNA screening in a future pregnancy, and another third would only have the screen under particular circumstances or if the scope of the panel was limited. Many women reported feeling misled by the information they received prior to accepting cfDNA screening or receiving their results.Conclusions: Study participants described issues with the clinical dialog when cfDNA screening is offered; when results are returned; and problems with the availability of information about the existence of false positives. These reports suggest that inadequate pretest discussion contributes to women's experience of decisional regret after receiving high-risk, false positive, or inconclusive results. Given the confusion about cfDNA screening accuracy, the prevalence of follow-up invasive tests, and the number of women who reported that they regretted choosing cfDNA screening, the mode of offering cfDNA should be reassessed.
Cell-Free DNA for the Management of Classical Hodgkin Lymphoma. [2021]Cell-free DNA (cfDNA) testing, is an emerging "liquid biopsy" tool for noninvasive lymphoma detection, and an increased amount of data are now available to use this technique with accuracy, especially in classical Hodgkin lymphoma (cHL). The advantages of cfDNA include simplicity of repeated blood sample acquisition over time; dynamic, noninvasive, and quantitative analysis; fast turnover time; reasonable cost; and established consistency with results from tumor genomic DNA. cfDNA analysis offers an easy method for genotyping the overall molecular landscape of pediatric and adult cHL and may help in cases of diagnostic difficulties between cHL and other lymphomas. cfDNA levels are correlated with clinical, prognostic, and metabolic features, and may serve as a therapeutic response evaluation tool and as a minimal residual disease (MRD) biomarker in complement to positron emission tomography (PET). Indeed, cfDNA real-time monitoring by fast high-throughput techniques enables the prompt detection of refractory disease or may help to address PET residual hypermetabolic situations during or at the end of treatment. The major recent works presented and described here demonstrated the clinically meaningful applicability of cfDNA testing in diagnostic and theranostic settings, but also in disease risk assessment, therapeutic molecular response, and monitoring of cHL treatments.
Application of circulating tumour DNA in terms of prognosis prediction in Chinese follicular lymphoma patients. [2023]Background: Follicular lymphoma (FL), an indolent non-Hodgkin lymphoma (NHL), is generally incurable. Favourable prognosis and durable remission are crucial for FL patients. The genetic mutation spectrum provides novel biomarkers for determining the prognosis of FL patients, but its detection is easily affected by the collection of tumour tissue biopsies. In this study, we aimed to describe the mutational landscape of FL using circulating tumour DNA (ctDNA) samples and to explore the relationship between mutations and prognostic indicators of clinical outcome in patients with newly diagnosed follicular lymphoma and the prognostic value of such mutations. Methods: A total of 28 patients with newly diagnosed FL were included in this study. A targeted NGS-based 59-gene panel was used to assess the ctDNA mutation profiles. Differences in clinical factors between patients carrying mutations and those without mutations were analysed. We also explored the relationship between gene mutation status, mean VAFs (variant allele frequencies) and clinical factors. The Kaplan‒Meier method was applied to analyse the overall survival (OS) and progression-free survival (PFS) of patients carrying mutations and those without mutations. Results: ctDNA mutations were detectable in 21 (75%) patients. The most commonly mutated genes were CREBBP (54%, 15/28), KMT2D (50%, 14/28), STAT6 (29%, 8/28), CARD11 (18%, 5/28), PCLO (14%, 4/28), EP300 (14%, 4/28), BCL2 (11%, 3/28), and TNFAIP3 (11%, 3/28), with a mutation frequency of >10%. Patients with detectable ctDNA mutation tended to present with advanced Ann Arbor stage (III-IV) (p = 0.009), high FLIPI risk (3-5) (p = 0.023) and severe lymph node involvement (No. of involved areas ≥5) (p = 0.02). In addition, we found that the mean VAF was significantly higher in patients with advanced Ann Arbor stage, high-risk FLIPI, elevated lactate dehydrogenase (LDH: 0-248U/L), advanced pathology grade, bone marrow involvement (BMI) and lymph node involvement. Additionally, KMT2D, EP300, and STAT6 mutations were associated with inferior PFS (p < 0.05). Conclusion: We described the ctDNA mutation landscapes in Chinese patients with newly diagnosed FL and found that ctDNA VAF means reflect tumour burden. Moreover, PFS was shorter in patients with KMT2D, EP300 and STAT6 mutations.
Integration of molecular testing for the personalized management of patients with diffuse large B-cell lymphoma and follicular lymphoma. [2023]Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) are the most common forms of aggressive and indolent lymphoma, respectively. The majority of patients are cured by standard R-CHOP immunochemotherapy, but 30%-40% of DLBCL and 20% of FL patients relapse or are refractory (R/R). DLBCL and FL are phenotypically and genetically hereterogenous B-cell neoplasms. To date, the diagnosis of DLBCL and FL has been based on morphology, immunophenotyping and cytogenetics. However, next-generation sequencing (NGS) is widening our understanding of the genetic basis of the B-cell lymphomas. In this review we will discuss how integrating the NGS-based characterization of somatic gene mutations with diagnostic or prognostic value in DLBCL and FL could help refine B-cell lymphoma classification as part of a multidisciplinary pathology work-up. We will also discuss how molecular testing can identify candidates for clinical trials with targeted therapies and help predict therapeutic outcome to currently available treatments, including chimeric antigen receptor T-cell, as well as explore the application of circulating cell-free DNA, a non-invasive method for patient monitoring. We conclude that molecular analyses can drive improvements in patient outcomes due to an increased understanding of the different pathogenic pathways affected by each DLBCL subtype and indolent FL vs R/R FL.
Monitoring of Circulating Tumor DNA Predicts Response to Treatment and Early Progression in Follicular Lymphoma: Results of a Prospective Pilot Study. [2023]Follicular lymphoma (FL) is the most frequent indolent non-Hodgkin lymphoma. Around 20% of patients suffer early disease progression within 24 months (POD24) of diagnosis. This study examined the significance of circulating tumor DNA (ctDNA) in predicting response to therapy and POD24 in patients with FL.
The role of circulating free DNA in the management of NSCLC. [2019]Circulating cell-free DNA (cfDNA) testing has emerged as an alternative to tumor tissue analyses for the management of metastatic non-small-cell lung cancer (NSCLC) patients. Analysis of cfDNA is a minimally invasive procedure that might better reflect tumor heterogeneity and allows repeated testing over the time. Areas covered: This review article covers the different applications of cfDNA testing in NSCLC: early diagnosis of the disease; detection of minimal residual disease in early lung cancer; identification of predictive and prognostic markers in advanced NSCLC patients; monitoring the response to therapy; assessment of tumor mutation burden. Expert commentary: The use of liquid biopsy is rapidly expanding to different applications. The combination of different circulating biomarkers (cfDNA, protein, miRNA) might improve the sensitivity and specificity of this approach in patients with low tumor burden. cfDNA testing is representing a valid source for molecular profiling in management of metastatic NSCLC patients and is providing important knowledge on tumor heterogeneity. Clinical trials are needed in order to transfer the information deriving from liquid biopsy testing in new therapeutic strategies.