Tumor Heterogeneity in Diffuse Large B-cell Lymphoma in Relation to CNS Involvement and Cell-free DNA

NCT04763148 | Completed DMC

• 1 other identifier: Heterogeneity in DLBCL
• Study Type: observational
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of the project is to clarify whether DLBCL exhibits mutational diversity among different lymph node tumors in one and the same patient. It is desired to find out whether a possible difference between lymph node tumors / tumors can explain why patients who initially (at diagnosis) have the same prognosis, sometimes have a completely different course, eg with rapid recurrence of the disease after treatment. A possible difference could also perhaps shed light on why disease in specific places spreads more frequently to the brain - and therefore have an impact on when one chooses to give preventive treatment against spread to the brain. Monitoring of circulating cell-free DNA (ctDNA) is a new, potential, non-invasive tool for measuring the full spectrum of genetic variations / mutations and is to be investigated in our study as a possible non-invasive assessment of diversity / heterogeneity.

Conditions

Lymphoma, Large B-Cell, Diffuse

Keywords

Lymphoma; Diffuse Large B-cell; Cell-free circulating DNA; Next Generation Sequencing; Heterogeneity

Outcome Measures

Primary Outcomes (1)

• Identify the pattern and variations of mutations in different lymphoma sites in individual patients

  Differences in mutations will be analyzed with next generation sequencing

  Through study completion, an average of 1. year

Secondary Outcomes (6)

• Identify inter-tumor heterogeneity between nodal and extra-nodal sites

  1 year

• Number of patients, with detected heterogeneity, who develop CNS disease, assessed over time

  1 year

• Clonal evolution will be assessed between primary tumor site and tumor at relapse

  1 year

• Assess if ctDNA can be used as monitorering of inter-tumor heterogeneity

  1 year

• Identify heterogeneity between nodal sites and bone-marrow biopsy

  1 year

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The prospective study will include two different cohorts: A: DLBCL patients with lymphoma involvement of several nodal sites accessible for biopsy and bone-marrow. B: DLBCL patients with both nodal, extra-nodal sites accessible for biopsy and bone-marrow. The prospective study will include newly diagnosed patients with DLBCL. Patients will be included in either cohort A or B according to localization of the disease ascertained by PET-CT to clarify nodal vs extra-nodal involvement.

You may qualify if:

• Diagnosed with DLBCL
• Immunochemotherapy (rituximab and CHOP-like chemotherapy) planned and not yet initiated (pretreatment with prednisolone is allowed)
• Age ≥ 18 years
• More than 1 lymphoma site accessible for biopsy
• Patient must consent to permit genetic analysis of their tumor biopsies
• Patient must consent to additional biopsies and blood samples
• Tumor biopsy and/or bone-marrow biopsy used for diagnosis available
• Patient must consent to access of their medical records to monitor the clinical process
• Written informed consent
• Baseline 18FDG-PET/CT available

You may not qualify if:

• History of previous or current malignancies
• Other previous/current hematological malignancies or inflammatory disease
• HIV
• Concurrent diagnosis of follicular lymphoma or other indolent lymphomas (composite histology)
• If the patient is deemed to have an acute treatment need, the patient cannot be included in the project.
• Patients on blood thinners, which must be paused before an additional biopsy, causing too much delay in initiating treatment will be excluded

Sponsors & Collaborators

• Herlev Hospital: lead

Study Sites (1)

Department of Hematology, Rigshospitalet

Copenhagen, 2100, Denmark

Location

Biospecimen

Retention: SAMPLES WITH DNA

Biospecimens will be analyzed with next generation sequencing technique.

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Anne Ortved Gang, MD

  Herlev Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Consultant

Study Record Dates

• First Submitted: February 11, 2021
• First Posted: February 21, 2021
• Study Start: January 12, 2022
• Primary Completion: December 1, 2022
• Study Completion: March 1, 2023
• Last Updated: March 6, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)