Measuring Cell-Free DNA (cfDNA) Levels in People With Follicular Lymphoma

Study Overview
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Brief Summary
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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.

Detailed Description
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This is a non-therapeutic protocol aimed to assess the ability of the s cfDNA assay to detect clinical response in FL when compared to conventional approaches for assessing response, such as PET-CT scans. Study assessments will include: 1) identification of the mutations present in the primary tumor, 2) identification of these mutations in the peripheral blood samples collected before initiation of standard therapy, after 2 cycles of therapy, at the completion of 6-8 cycles of induction therapy, and then every 6 months for a total of 2 years from the initiation of therapy using a cfDNA assay. For patients who receive RT, peripheral blood samples will be collected before initiation of RT, and then 3 months, 6 months, 12 months, 18 months and 24 months post RT using a s cfDNA assay.

Official Title
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An Exploratory Study to Correlate the Level of Cell-free DNA With Response to First-line Treatment in Patients With Follicular Lymphoma

Conditions
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Follicular Lymphoma

Intervention / Treatment
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* Diagnostic Test: cfDNA testing
* Other: sample of saliva or fingernail clipping
* Diagnostic Test: pre-treatment test specimen
* Diagnostic Test: PET/CT, CT, or MRI testing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥18 years of age at time of signing informed consent. Consent is permitted from either the participant or from a Legally Authorized Representative (LAR) on their behalf. Histology-confirmed follicular lymphoma grade 1-3a, verified by the enrolling institution Ability to adhere to the study visit schedule and all the protocol requirements Measurable FDG-avid disease Not applicable for retrospective patients in CR Exclusion Criteria: Patients receiving second or greater line of therapy (except in retrospective cohort of long-term survivors of FL [i.e. >10 years out from frontline treatment])

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a non-therapeutic protocol. The intervention in this study will involve collection of a standard-of-care pre-treatment tumor biopsy (archival tissue, if available) to identify the tumor-specific s cfDNA signature.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prospective Group<br>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 | Diagnostic Test: cfDNA testing<br>* peripheral blood samples collected before initiation of standard therapy, after 2 cycles of therapy, at the completion of 6-8 cycles of induction therapy, and then every 6 months for a total of 2 years from the initiation of therapy using a cfDNA assay. For retrospective patients, blood samples will be collected once.<br>Other: sample of saliva or fingernail clipping<br>* collected in clinic one time<br>Diagnostic Test: pre-treatment test specimen<br>* From bone marrow, blood, lymph node, or alternate site to identify tumor-specific mutations. For retrospective patients initial tumor tissue (if available).<br>Diagnostic Test: PET/CT, CT, or MRI testing<br>* PET/CT scans are required at baseline and at the patient's end-of-treatment visit. The other standard-of-care scan timepoints can be performed using PET/CT, dedicated CT, or MRI per the treating investigator's discretion.<br>|
| Experimental: Retrospective Group<br>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. | Diagnostic Test: cfDNA testing<br>* peripheral blood samples collected before initiation of standard therapy, after 2 cycles of therapy, at the completion of 6-8 cycles of induction therapy, and then every 6 months for a total of 2 years from the initiation of therapy using a cfDNA assay. For retrospective patients, blood samples will be collected once.<br>Other: sample of saliva or fingernail clipping<br>* collected in clinic one time<br>Diagnostic Test: pre-treatment test specimen<br>* From bone marrow, blood, lymph node, or alternate site to identify tumor-specific mutations. For retrospective patients initial tumor tissue (if available).<br>Diagnostic Test: PET/CT, CT, or MRI testing<br>* PET/CT scans are required at baseline and at the patient's end-of-treatment visit. The other standard-of-care scan timepoints can be performed using PET/CT, dedicated CT, or MRI per the treating investigator's discretion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| whether the assay can correctly identify presence of disease in patients with measurable disease | Response will be evaluated using the updated response criteria entitled, The Lugano Classification system. The investigator will use of the 5-point scale for visually assessing response on the pre- and end-of-treatment FDGPET/CT scans. This scale is commonly referred to as the Deauville criteria; it was developed by international experts in the field at the First International Workshop on interim-PET in Lymphoma in Deauville in 2009 and is routinely applied to patients undergoing lymphoma directed therapy. The 5-point scale is described in the table below. 1 No residual uptake 2 Uptake ≤ mediastinum 3 Uptake > mediastinum but ≤ liver 4 Uptake moderately > liver 5 Markedly increased uptake at any site or progression | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cell-free DNA, 20-199