Liquid Biopsy to Enable Diagnostics and Monitoring for Immune-mediated Lymphoproliferative Disorders

Lymphoproliferative Disorders Clinical Trial

— LIMPID  

Official title:

Liquid Biopsy-based Genomic Assay to Enable Non-invasive Precision Diagnostics and Monitoring for Immune-mediated Lymphoproliferative Disorders (ILD)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05803616
• Other study ID #: 2021-01016
• Status: Recruiting
• Start date: May 23, 2022
• Est. completion date: December 31, 2025

Study information

• Verified date: April 2023
• Source: University Hospital, Geneva
• Contact: Noemie Lang, MD
• Phone: +41795532406
• Email: noemie.lang[@]hcuge.ch
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Immune-mediated lymphoproliferative disorders (ILD), as per World Health Organization (WHO HAEM 5) classification, are rare conditions associated with a poor outcome. Current management of ILD is focusing on prevention (e.g.) early detection of ILD with preemptive Epstein Barr virus (EBV) Deoxyribonucleic acid (DNA) levels monitoring, however, this approach is useless for the early detection of EBV-negative ILD. Therapeutic management consists of a reduction in immunosuppressive therapy (RIS), allowing mostly partial and transient responses. Rituximab, an anti-CD20 (cluster differentiation 20) antibody, provides roughly 20-25% of complete and durable responses, thus the majority of ILD patients will require immunochemotherapy, burden with significant toxicity in this challenging population. Implementation of liquid biopsy, also called circulating tumor DNA (ctDNA) in plasma or serum is an area of investigation that is becoming increasingly relevant for clinical practice, allowing for non-invasive monitoring of disease status.

Early detection and monitoring of ILD using ctDNA may allow for preemptive therapy, improved risk-stratification and ultimately, lead to outcome improvement. This multicenter Swiss project will allow a better understanding of ILD mutational landscape and pathogenesis, which could lead to the development of new screening and monitoring approaches for patients suffering from ILD.

Description:

In this observational prospective study, the investigators will collect clinical data from subjects' charts through a dedicated multicenter electronic case report form (eCRF).

Whenever available, PET-CT will be transferred through a Web-based Imaging and Diagnosis Exchange Network (WIDEN) to perform a blinded independent review of staging and response.

Biological samples included 20 ml of blood collected at each of the following planned clinical points in time: i) at ILD diagnosis, ii) after first cycle of therapy, iii) at interim response assessment, iv) at the end-of-treatment, v) at 3 months follow-up, vi) at 12 months follow-up, vii) at disease progression, if applicable. Additional samples could be collected if clinically relevant.

Additionally, the investigators will request formalin-fixed and paraffin-embedded tissue (FFPET) or fresh-frozen (FF) tissue slices/blocks at ILD diagnosis from Pathology Departments of participating Centers for retrospective ILD subjects.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Any patient with a diagnosis of ILD defined by the World Health Organization (WHO HAEM 5)(e.g. post-transplant setting, X-link, concomitant auto-immune disorders)

Exclusion Criteria:

• Lymphoproliferative disorders non immune-mediated

• Lymphoproliferative disorders occurring in the context of a concomitant human immunodeficiency virus (HIV) infection

Related Conditions & MeSH terms

• Disease
• Lymphoproliferative Disorders

Intervention

Diagnostic Test:
• Liquid biopsy
ctDNA measured in the plasma and analyse by next generation sequencing (NGS) for minimal residual disease (MRD)

Locations

Country	Name	City	State
Switzerland	Basel University Hospital	Basel
Switzerland	Oncology Institute of Southern Switzerland	Bellinzona
Switzerland	Inselspital	Bern
Switzerland	Hôpitaux Universitaires de Genève (HUG)	Geneva
Switzerland	Kantonsspital	St Gallen
Switzerland	University Hospital Zu¨rich	Zürich

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Geneva

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Predictive value of ctDNA to monitor response in ILD (MRD) using NGS	Molecular response (minimal residual disease, MRD) during therapy in ILD diagnosed patients will be monitored using regular liquid biopsy (ctDNA) and assessing the presence or not of genomic aberrations present at baseline if any.	2 years
Secondary	Characterisation of ILD tumour microenvironment and genetic / epigenetic landscape	Tumour microenvironment and genetic / epigenetic landscape will be explored using various techniques such as NGS, multiplex immunohistochemistry, digital droplet Polymerase Chain Reaction (ddPCR) and methyloma assays.	2 years