Non-invasive Tumor Immunoglobulin Gene Next Generation Sequencing (IgNGS) in Diffuse Large B Cell Lymphoma (DLBCL)

NCT ID: NCT04237168

Last Updated: 2020-01-29

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 30 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-01-31
• Study Completion Date: 2022-07-31

Brief Summary

This study will evaluate IgNGS at different time points in newly diagnosed DLBCL patients homogeneously treated (RCHOP) to address its correlation with conventional techniques (i.e., positron emission tomography/computed tomography imaging (PET/CT) and outcome.

Detailed Description

In B-cell malignancies, every lymphocyte clone expresses a unique antigen receptor structure, therefore immunoglobulin gene rearrangements (the sequence of nucleotides at the V(D)J recombination site) serves as a specific marker for each clone. Methods of analysis have changed over time to improve the sensitivity and to allow its application in clinical settings.

Diffuse Large B-cell lymphoma (DLBCL) displays molecular heterogeneity. In this context, IgNGS allows for detection of tumor clonotype from plasma (ctDNA) (Liquid Biopsy-LB) of DLBCL patients with high sensitivity and specificity. ctDNA can be tracked with this methodology in the vast majority (>90%) of patients, in contrast to NGS-methods based on genotyping for specific DLBCL mutations, which have overall low frequency. Furthermore, most newly discovered neoantigens in lymphoma derive from immunoglobulin variable sequences, supporting the relevance of the analysis of this particular region in contrast to the use of specific B-cell mutations. Importantly, preliminary studies on clonotype detection by IgNGS at the end of treatment correlate with outcome (poorer progression-free survival) and the persistence or reemergence of the tumor clonotype by ctDNA studies may anticipate the clinical relapse. We propose to evaluate IgNGS at different time points in newly diagnosed DLBCL patients treated with RCHOP to address its correlation with conventional techniques (i.e., PET/CT imaging) and outcome.

Conditions

Lymphoma, Large B-Cell, Diffuse

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

DLBCL patients

newly diagnosed DLBCL (de novo, all ages) patients treated with RCHOP (first-line treatment regimen)

IgNGS from circulating tumor DNA

Intervention Type: DIAGNOSTIC_TEST

3 longitudinal plasma samples will be evaluated at three different time points per patient: 0 (pre-treatment), end of treatment, and at 6 months after treatment.

Interventions

IgNGS from circulating tumor DNA

3 longitudinal plasma samples will be evaluated at three different time points per patient: 0 (pre-treatment), end of treatment, and at 6 months after treatment.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Exclusion Criteria

• Primary mediastinal DLBCL.
• Transformed DLBCL
• Patients HIV+
• Central Nervous System (CNS) DLBCL

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Javier Briones

Role: PRINCIPAL_INVESTIGATOR

Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

Locations

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Countries

Spain

Central Contacts

Javier Briones, PhD

Role: CONTACT

jbriones@santpau.cat

+34935565649

Anna Monter-Rovira, MD

Role: CONTACT

amonter@santpau.cat

Facility Contacts

Javier Briones, PhD

Role: primary

jbriones@santpau.cat

Anna Monter-Rovira, MD

Role: backup

amonter@santpau.cat

References

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

PMID: 27831904 (View on PubMed)

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

PMID: 25887775 (View on PubMed)

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Reference Type: BACKGROUND

PMID: 25842160 (View on PubMed)

Other Identifiers

IIBSP-LIN-2019-83

Identifier Type: -

Identifier Source: org_study_id