Clinical trial NCT05803616: Liquid Biopsy to Enable Diagnostics and Monitoring for Immune-mediated Lymphoproliferative Disorders
Official title: Liquid Biopsy-based Genomic Assay to Enable Non-invasive Precision Diagnostics and Monitoring for Immune-mediated Lymphoproliferative Disorders (ILD)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Lymphoproliferative Disorders
Lymphoproliferative Disorder Following Transplantation
Keywords: Immune-related Lymphoproliferative Disorders
Lead sponsor: University Hospital, Geneva
Sponsor class: OTHER
First posted: 2023-04-07
Enrollment: 20
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All patients newly diagnosed or relapsing from an ILD as per World Health Organization (WHO HAEM 5) classification

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.

Eligibility criteria: 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

Primary outcomes:
measure: Predictive value of ctDNA to monitor response in ILD (MRD) using NGS
timeFrame: 2 years
Secondary outcomes:
measure: Characterisation of ILD tumour microenvironment and genetic / epigenetic landscape
timeFrame: 2 years
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: Basel University Hospital
city: Bellinzona
country: Switzerland
facility: Oncology Institute of Southern Switzerland
city: Bern
country: Switzerland
facility: Inselspital
city: Geneva
country: Switzerland
facility: Hôpitaux Universitaires de Genève (HUG)
city: St Gallen
country: Switzerland
facility: Kantonsspital
city: Zürich
country: Switzerland
facility: University Hospital Zürich
Study officials:
affiliation: Geneva Univresity Hospital
name: Noemie Lang, MD
role: PRINCIPAL_INVESTIGATOR
References: