Biomarkers for Diagnostic, Prognostic and of Response to Treatment in Adult Langerhans Cell Histiocytosis

NCT ID: NCT06197204

Last Updated: 2024-07-17

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 570 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-03-25
• Study Completion Date: 2034-03-25

Brief Summary

Adult Langerhans histiocytosis (LCH) is a rare disease of unknown etiology, characterized by the activation of the MAPK (Mitogen-activated protein kinases) pathway, driven by various somatic mutations in the specific lesions of involved organs/tissues. LCH is currently classified as myeloid neoplasia with an inflammatory component. In patients with active systemic LCH, MAPK mutations may also be identified in plasma free cell DNA in patients. In contrast, circulating MAPK mutations seem more rarely detected in patients with LCH limited to a single organ/tissue (single system disease), but this has not been accurately assessed in a large series of patients.

The clinical presentation of LCH is very diverse, the prognosis variable, and the evolution marked by the occurrence of flares of the disease. A definitive diagnosis of LCH warrants histological confirmation obtained by a biopsy of an involved organ. In case of Pulmonary Langerhans cell histiocytosis (PLCH), a presumptive diagnosis is often acceptable when lung-computed tomography (CT) shows a nodulo-cystic pattern after excluding alternative diagnoses. In contrast, in case of purely cystic lung CT pattern, PLCH may be difficult to differentiate from other diffuse cystic lung diseases (mainly lymphangioléiomyomatose (LAM) and BHD (Birt-Hogg-Dubé syndrom), and eventually other rare disorders). Advanced PLCH may even be misdiagnosed as pulmonary emphysema that also occurs in smokers. In these situations, confirmation of PLCH warrants lung tissue, obtained most often by surgical lung biopsy that comprises significant morbidity or is not feasible in patients with altered lung function. Thus, the identification of specific blood biomarkers of cystic PLCH would be very useful.

On another hand, personalized management of adult patients with LCH is limited given the absence of predictive factors for prognosis or response to treatment.

The aim of this prospective study is to describe precisely the clinical phenotype at diagnosis and during follow-up of a large cohort of adult LCH patients and to seek for blood biomarkers eventually associated with prognosis or response to specific treatment. For patients with cystic PLCH specific markers for non-invasive diagnosis will also be investigated.

In the subgroup of patients with Single system (SS) LCH and specific driver MAPK mutation in tissue lesions, we will also look for the identification of this mutation in plasma free DNA at the time of a flare of the disease.

Conditions

Histiocytosis, Langerhans-Cell

Study Design

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

Study Groups

LCH patients

Blood sampling

Intervention Type: OTHER

• at first visit in the reference center
• at each follow-up visit ( once a year)
• before and after specific treatment
• in case of flare

Biopsy

Intervention Type: OTHER

In case of flare

Control group

• diffuse lung cystic disease
• pulmonary emphysema
• healthy smokers

Blood sampling

Intervention Type: OTHER

Once at inclusion visit

Interventions

Blood sampling

• at first visit in the reference center
• at each follow-up visit ( once a year)
• before and after specific treatment
• in case of flare

Intervention Type: OTHER

Biopsy

In case of flare

Intervention Type: OTHER

Blood sampling

Once at inclusion visit

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

LCH patients :

• Age ≥ 18 years
• All confirmed LCH seen at the reference center whatever the clinical presentation

Controls :

• Age ≥ 18 years
• Patients with diffuse lung cystic disease, pulmonary emphysema and healthy smokers

All :

• Signing an informed consent
• Patients with health insurance

Exclusion Criteria

• Persons under guardianship or curatorship, or deprived of freedom by a judicial or administrative decision.
• People benefiting from Medical Aid from the State (AME)
• Pregnant women, parturient and mothers who are breastfeeding.
• Persons subject to psychiatric care and persons admitted to a health or social establishment for purposes other than research
• Persons unable to express their consent

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Hopital Saint Louis

Paris, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Abdellatif Tazi, Pr

Role: CONTACT

abdellatif.tazi@aphp.fr

+33142499618

Jérôme Lambert, Pr

Role: CONTACT

jerome.lambert@u-paris.fr

+33142499742

Facility Contacts

Abdellatif Tazi, Pr

Role: primary

Other Identifiers

APHP230748

Identifier Type: -

Identifier Source: org_study_id