Biomarkers in Systemic Histiocytosis

NCT ID: NCT07157683

Last Updated: 2025-09-05

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Total Enrollment: 500 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-10-01
• Study Completion Date: 2040-10-01

Brief Summary

Systemic histiocytoses in adults (Langerhans cell histiocytosis, Erdheim-Chester disease, and Rosai-Dorfman disease) are rare inflammatory disorders in which recent discoveries have identified a clonal origin, with activating mutations in the MAP kinase pathway, enabling access to targeted therapies. However, the mechanism by which these mutations induce an inflammatory profile in tissue histiocytes remains largely unknown.

Despite these advances, there is a clear need to refine diagnostic and prognostic classification, to identify the biological mechanisms involved in the onset and progression of these diseases, to develop new targeted strategies, and to establish minimally invasive monitoring methods (liquid biopsies).

This project aims to make a decisive contribution toward these goals.

Detailed Description

Systemic histiocytoses are rare diseases with a clinical spectrum ranging from mild forms to severe, life-threatening multi-organ involvement. Numerous recent studies have identified somatic mutations in the MAP kinase pathway in tissue-infiltrating histiocytes, providing a better understanding of the disease pathophysiology and enabling access to more effective targeted therapies. However, due to the extreme rarity of these diseases, many unknowns remain.

These mutations do not appear to induce a proliferative oncogenic process, as seen in cancers where similar mutations have been identified. Instead, they seem to trigger a pro-inflammatory and pro-fibrotic immune response, ultimately leading to organ damage. The immune mechanisms induced by these mutations in histiocytes remain unexplored.

There are also currently no reliable data to accurately predict disease progression, including survival, treatment response, remission, or organ involvement.

It is therefore essential to establish patient cohorts to improve disease understanding and to identify effective diagnostic, prognostic, and predictive biomarkers-whether for standard treatment response or as potential theranostic markers (actionable by a specific treatment).

Conditions

Systemic Histiocytosis (Disorder)

Study Design

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

Interventions

Biospecimen collection

If a blood sample is drawn as part of standard care, up to six additional EDTA tubes (42 mL max) will be collected for research.

In addition, the following optional samples may be collected, depending on investigator assessment and/or patient preference:

• Saliva sample (if no blood draw is performed)
• Urine sample
• Stool sample"

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Age ≥ 18 years
• Patient followed for systemic histiocytosis in Internal Medicine Department 2 at Pitié-Salpêtrière Hospital
• Non-opposition to participation in the study

Exclusion Criteria

• Pregnant or breastfeeding women
• Patients without French social security or covered by State Medical Aid (AME)
• Patients deprived of liberty by judicial or administrative decision, or under legal protection

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Internal Medicine Department 2 at Pitié-Salpêtrière Hospital

Paris, , France

Countries

France

Facility Contacts

Matthias PAPO, MD,PhD

Role: primary

matthias.papo@aphp.fr

1 84 82 81 73 ext. +33

Julien HAROCHE, MD,PhD

Role: backup

julien.haroche@aphp.fr

1 84 82 62 25 ext. +33

Other Identifiers

APHP250660

Identifier Type: -

Identifier Source: org_study_id