Clinical trial NCT06197204: Biomarkers for Diagnostic, Prognostic and of Response to Treatment in Adult Langerhans Cell Histiocytosis
Official title: Biomarqueurs Diagnostiques, Pronostiques et de réponse au Traitement Dans l'Histiocytose Langerhansienne de l'Adulte
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Histiocytosis, Langerhans-Cell
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2024-01-09
Enrollment: 570
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All adult patients with LCH seen at the French reference center for histiocytoses.

For the study on the diagnostic performance of blood biomarkers for cystic PLCH, a comparative group of patients with diffuse lung cystic diseases, pulmonary emphysema and healthy smokers will be included.

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.


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

Primary outcomes:
measure: Description of the clinical phenotype at diagnosis and the outcome of adult LCH patients
timeFrame: Up to 10 years
Secondary outcomes:
measure: Evaluation of the prognostic performance of blood biomarkers for adult LCH patients
timeFrame: Up to 10 years
measure: Evaluation of the predictive performance of blood biomarkers for the therapeutic response
timeFrame: Up to 10 years
measure: Evaluation of the diagnostic performance of blood biomarkers for patients with purely cystic Pulmonary Langerhans cell histiocytosis
timeFrame: Up to 10 years
measure: Evaluation of the presence of MAPK tissue mutation in plasma cell free DNA for patients with Single System LCH at the time of a flare of the disease
timeFrame: Up to 10 years
Other outcomes:
Locations:
city: Paris
country: France
facility: Hopital Saint Louis
Study officials:
References: