Development of a Tissue-Based & Cell Free DNA Next-Generation Sequencing Workflow

Study Overview
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Brief Summary
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Develop a Next-Generation Sequencing (NGS) workflow for mutation profiling of formalin-fixed paraffin-embedded (FFPE) tissue and cell-free DNA (cfDNA) specimens. Calculate the proportion of cases in a test series of B-cell non-Hodgkin Lymphomas (BNHL) with somatic mutations or immunoglobulin heavy chain (IGH) gene rearrangements common to both FPPE and cfDNA specimens. Determine if certain types of BNHL are more likely to have mutation profiles common to both FFPE & corresponding cfDNA (FFPE-cfDNA dyads) Determine if specific mutations or mutation profiles in FFPE or cfDNA specimens (or both) are of prognostic value after a clinical follow-up of 2 years from the time of diagnosis.

Detailed Description
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Patients with newly diagnosed B cell NHL will be identified. Samples will be cored from their diagnostic FFPE blocks and assayed to find lymphoma specific variants and immunoglobulin heavy chain gene rearrangements. Blood samples collected at baseline will be compared to see if variants and rearrangements can be detected in tumor specific DNA based on previous studies. Participant data will be collected, and clinical outcomes will be assessed to determine effect of mutation profiles on outcomes over 2 year follow up. Blood samples will be prospectively collected at scheduled follow up and if primary objectives of this study are met, will be assessed for presence of cfDNA and impact of variation on clinical outcomes.

Official Title
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Development of a Tissue-Based & Cell Free DNA Next-Generation Sequencing Workflow

Conditions
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Non-Hodgkin Lymphoma

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: New diagnosis of B cell NHL Willing to have blood collected at timepoints of regularly scheduled follow up Formalin fixed paraffin embedded (FFPE) diagnostic specimen sufficient for further testing Exclusion Criteria: Unwilling or unable to participate in follow up

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| B cell Non-Hodgkin Lymphoma<br>18 years of age or older with new diagnosis of non-Hodgkin lymphoma with FFPE specimen demonstrating enough tissue for elucidation of lymphoma specific variant and immunoglobulin clonotype, willing to provide baseline and follow up bloodwork to look for presence of variant and clonotype. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2 year Progression Free Survival | Recorded in percentage. To determine impact of lymphoma specific mutation on outcome. | 2 years from diagnosis of B cell non-Hodgkin Lymphoma | 
| 2 year Overall Survival | Recorded in percentage. To determine impact of lymphoma specific mutation on outcome. | 2 years from diagnosis of B cell non-Hodgkin Lymphoma | 
| Occurrence of lymphoma specific mutations or detectable IgH rearrangements in circulating tumor specific DNA in blood samples at baseline | Proportion of cases of BNHL with somatic mutations or IgH gene rearrangements detectable in blood. Will be recorded in percentage, and determined at baseline. | Determined at baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cell free DNA, Next Generation Sequencing