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

Recruiting

• Conditions: Lymphoproliferative Disorders; Lymphoproliferative Disorder Following Transplantation
• Interventions: Diagnostic Test: Liquid biopsy

• Registration Number: NCT05803616
• Lead Sponsor: University Hospital, Geneva

Brief 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.

Detailed 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.

Study Timeline

• Study Start: 2022-05-23
• Study First Submitted: 2023-03-09
• Study First Submitted QC: 2023-03-24
• Status Verified: 2023-04
• Study First Posted: 2023-04-07
• Last Update Submitted: 2023-04-21
• Last Update Posted: 2023-04-25
• Primary Completion: 2023-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
ILD group	Liquid biopsy	All patients newly diagnosed or relapsing from an ILD could be enrolled in this observational study

Primary Outcome Measures

Name	Time	Method
Predictive value of ctDNA to monitor response in ILD (MRD) using NGS	2 years	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.

Secondary Outcome Measures

Name	Time	Method
Characterisation of ILD tumour microenvironment and genetic / epigenetic landscape	2 years	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.

Trial Locations

Locations (6)

Inselspital; 🇨🇭 Bern, Switzerland

Oncology Institute of Southern Switzerland; 🇨🇭 Bellinzona, Switzerland

University Hospital Zürich; 🇨🇭 Zürich, Switzerland

Basel University Hospital; 🇨🇭 Basel, Switzerland

Hôpitaux Universitaires de Genève (HUG); 🇨🇭 Geneva, Switzerland

Kantonsspital; 🇨🇭 St Gallen, Switzerland