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

NCT06197204 | Recruiting

• 1 other identifier: APHP230748
• Study Type: observational
• Target: 570
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Description of the clinical phenotype at diagnosis and the outcome of adult LCH patients

  Up to 10 years

Secondary Outcomes (4)

• Evaluation of the prognostic performance of blood biomarkers for adult LCH patients

  Up to 10 years

• Evaluation of the predictive performance of blood biomarkers for the therapeutic response

  Up to 10 years

• Evaluation of the diagnostic performance of blood biomarkers for patients with purely cystic Pulmonary Langerhans cell histiocytosis

  Up to 10 years

• 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

  Up to 10 years

Study Arms (2)

LCH patients

Other: Blood sampling; Other: Biopsy

Control group

* diffuse lung cystic disease * pulmonary emphysema * healthy smokers

Other: Blood sampling

Interventions

Blood sampling 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

LCH patients

Biopsy OTHER

In case of flare

LCH patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Hopital Saint Louis

Paris, France

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood sampling

MeSH Terms

Conditions

Histiocytosis, Langerhans-Cell

Interventions

Blood Specimen Collection; Biopsy

Condition Hierarchy (Ancestors)

Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical

Central Study Contacts

Abdellatif Tazi, Pr

CONTACT

+33142499618; abdellatif.tazi@aphp.fr

Jérôme Lambert, Pr

CONTACT

+33142499742; jerome.lambert@u-paris.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 26, 2023
• First Posted: January 9, 2024
• Study Start: March 25, 2024
• Primary Completion (Estimated): March 25, 2034
• Study Completion (Estimated): March 25, 2034
• Last Updated: July 17, 2024

Record last verified: 2024-07

Locations

FR (1)