ECD-Score: a Study on Erdheim-Chester Disease

NCT07454343 | Recruiting

• 1 other identifier: ECD-Score
• Study Type: observational
• Target: 1,000
• Locations: 4 countries
• Sites: 7

Brief Summary

Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis that primarily affects adults but may also occur in pediatric patients. It is characterized by the accumulation of foamy histiocytes with a distinctive immunophenotype in multiple anatomical sites, most commonly the long bones, retroperitoneal and perirenal tissues, the heart, the central nervous system, and the pituitary gland. The disease shows marked clinical heterogeneity, ranging from localized and asymptomatic forms to severe manifestations with multiorgan involvement. From a pathogenetic perspective, ECD is mainly driven by gain-of-function mutations affecting the MAPK and PI3K-AKT pathways, particularly the BRAFV600E mutation, leading to aberrant activation of the MAPK and mTOR signaling pathways. The release of pro-inflammatory cytokines and chemokines plays a key role in systemic inflammation and tissue damage, resulting in significant complications and disability depending on the organs involved. Despite the significant efforts of international research in recent years, particularly given the extreme rarity of the disease (incidence below 5 cases per 10,000,000 adults per year), substantial knowledge gaps remain, especially with regard to the prediction of long-term outcomes, both in terms of survival and disability. Although some prognostic factors associated with survival have already been identified (such as central nervous system involvement), to date only limited-scale studies have systematically evaluated the prognosis of patients with ECD, focusing in particular on factors influencing organ-specific complications. Moreover, in clinical practice, several aspects that significantly affect patients' quality of life tend to be underestimated, partly due to the time required to perform comprehensive assessments using detailed questionnaires designed to quantify disease-related consequences, such as chronic disability, depression, and cognitive impairment. Nevertheless, there is a growing need for and interest in these parameters, commonly referred to as patient-reported outcomes. In light of these considerations, the development and implementation of a comprehensive prognostic score aimed at predicting survival and long-term disease outcomes could improve the overall assessment of patients and provide more accurate and clinically meaningful prognostic information.

Conditions

Erdheim-Chester Disease (ECD)

Outcome Measures

Primary Outcomes (8)

• Overall survival

  The time from the patient's enrollment in the study until death or the last available follow-up

  5 years

• Association between belonging to a clinical cluster and survival

  Clinical cluster of ECD

  5 years

• Association between organ damage and survival

  organ damage related to the disease (e.g., chronic kidney failure)

  5 years

• Association between the treatment used (relative to the historical period) and survival

  treatment received

  5 years

• Association between response to treatment and survival

  complete response rate, partial response, stable disease, progression

  5 years

• Association between treatment toxicity and survival

  incidence and severity of adverse events (classified according to CTCAE v6.0)

  5 years

• Association between comorbidities and survival

  presence of malignant tumors and other chronic diseases

  5 years

• Association between geographical origin and survival

  geographical origin

  at enrollment

Secondary Outcomes (2)

• Incidence of comorbidities secondary to the disease or treatment (e.g., secondary malignancies)

  5 years

• Association between disease and quality of life

  5 years

Study Arms (1)

patients with Erdheim-Chester disease (ECD)

Patients with ECD will be recruited and will attend outpatient visits at the study coordination center at the Meyer IRCCS University Hospital (Florence) and other participating centers. The patients to be enrolled will be "prevalent" and "incident" patients during the 5-year study period. Patients undergoing follow-up at their respective centers will be involved in the study, as well as those who receive a new diagnosis of ECD during the study period. Clinical data will be collected from all patients included, focusing primarily on organ involvement and response to treatment. They will also be asked to complete questionnaires on quality of life and other specific outcomes. Epidemiological data will also be considered, in particular the geographical origin of patients, and survival rates will also be evaluated.

Eligibility Criteria

• Age: 7 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients with ECD will be recruited and will attend outpatient visits at the study coordination center at the Meyer IRCCS University Hospital (Florence) and other participating centers. The patients to be enrolled will be "prevalent" and "incident" patients during the 5-year study period. Patients undergoing follow-up at their respective centers will be involved in the study, as well as those who receive a new diagnosis of ECD during the study period.

You may qualify if:

• informed consent signed by the patient or, for minors, by a parent or legal guardian
• confirmed diagnosis of ECD according to the latest international guidelines (Goyal G, Blood 2020)
• availability of clinical, molecular, treatment and response to therapy data
• a minimum follow-up period of one year.

You may not qualify if:

• lack of diagnostic or follow-up data
• refusal or inability to sign the informed consent form

Sponsors & Collaborators

• Meyer Children's Hospital IRCCS: lead

Study Sites (7)

National Institute of Health

Bethesda, Maryland, 20892, United States

NOT YET RECRUITING

Mayo Clinic

Rochester, Minnesota, 55902, United States

NOT YET RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

NOT YET RECRUITING

Hopital Pitiè-Salpetriere

Paris, France

NOT YET RECRUITING

Meyer Children's Hospital IRCCS, Firenze

Florence, Fi, 50134, Italy

RECRUITING

San Raffaele Hospital

Milan, Italy, Italy

NOT YET RECRUITING

Newcastle Upon Tyne Hospitals NHS Foundation Trust

Newcastle, Newcastel, United Kingdom

NOT YET RECRUITING

MeSH Terms

Conditions

Erdheim-Chester Disease

Condition Hierarchy (Ancestors)

Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Augusto Vaglio, Medical Doctor

  Meyer Children's Hospital IRCCS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Augusto Vaglio, Medical Doctor

CONTACT

055 5662905; augusto.vaglio@meyer.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 2, 2026
• First Posted: March 6, 2026
• Study Start: December 23, 2024
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: March 6, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3); FR (1); GB (1); IT (2)