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

• Conditions: Non-Hodgkin Lymphoma

• Registration Number: NCT02788084
• Lead Sponsor: Alberta Health Services, Calgary

Brief Summary

1. Develop a Next-Generation Sequencing (NGS) workflow for mutation profiling of formalin-fixed paraffin-embedded (FFPE) tissue and cell-free DNA (cfDNA) specimens.

2. 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.

3. Determine if certain types of BNHL are more likely to have mutation profiles common to both FFPE \& corresponding cfDNA ("FFPE-cfDNA dyads")

4. 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

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.

Study Timeline

• Study First Submitted: 2016-05-25
• Study First Submitted QC: 2016-05-27
• Study First Posted: 2016-06-02
• Study Start: 2016-10
• Primary Completion: 2019-06
• Status Verified: 2020-01
• Last Update Submitted: 2020-01-07
• Last Update Posted: 2020-01-10
• Study Completion: 2021-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 80

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
2 year Progression Free Survival	2 years from diagnosis of B cell non-Hodgkin Lymphoma	Recorded in percentage. To determine impact of lymphoma specific mutation on outcome.
2 year Overall Survival	2 years from diagnosis of B cell non-Hodgkin Lymphoma	Recorded in percentage. To determine impact of lymphoma specific mutation on outcome.
Occurrence of lymphoma specific mutations or detectable IgH rearrangements in circulating tumor specific DNA in blood samples at baseline	Determined 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.

Trial Locations

Locations (1)

Tom Baker Cancer Centre; 🇨🇦 Calgary, Alberta, Canada