Active clinical trials for "Erdheim-Chester Disease"

The study we propose is a pilot phase II, interventional, treatment, open-label, single-arm, efficacy/safety clinical trial of a 6-month treatment with tocilizumab (8 mg/kg once monthly) in adult patients with extraskeletal Erdheim-Chester disease (ECD). Efficacy will be assessed as the effect of the treatment on the size of the measurable lesions, as evaluated by bidimensional measurements, and by the impact of the treatment on symptom control and on patient quality of life. Safety of the treatment will be determined by the analysis of adverse events and of the relevant safety laboratory parameters. Secondary objectives of the study will be: to better characterize the mechanisms underlying such disease and the possible response to the treatment. In particular: i) we will investigate the immunophenotypic and histomorphologic features of ECD histiocytes; ii) we will gather gene expression data from peripheral blood immune cells to better characterize their functional status, to define their transcriptional fingerprints and their possible modulation as a result of tocilizumab treatment; iii) we will assess the production of soluble mediators and the expression of activation molecules by monocytes derived from ECD patients, as well as after stimulation with selected inflammatory cytokines; iv) we will investigate the ex vivo and in vitro impact of tocilizumab treatment on those markers, for possible use as a predictor or indicator of response to treatment. to investigate the metabolic pattern in ECD patients before and after tocilizumab treatment as evaluated by fluoro-d-glucose positron emission tomography (FDG-PET) and to verify if it can be an indicator of ECD activity.

Erdheim-Chester Diseases (ECD) is a very rare non-Langerhans cell histiocytosis of unknown origin and pathogenesis. It has been reported mainly in adult males over the age of 40 years, although cases have been reported in females as well. Children are rarely affected. Mutation of the BRAF gene, specifically BRAFV600E, has been recently identified in 50% of Erdheim Chester lesions in a French cohort. This somatic mutation is believed to be the driver mutation in positive cases. The clinical characteristics of ECD range from asymptomatic to multisystemic involvement; longitudinal progression and natural history are becoming better understood. ECD commonly affects the bones, kidneys, retroperitoneal space, skin and brain. If untreated, the disease progresses rapidly, causing fatal outcomes due to severe lung disease, chronic renal failure, cardiomyopathy and other complications. The diagnosis of ECD relies upon imaging studies and specific pathologic findings in biopsies of affected organs, i.e., fibrosis and infiltration of tissues with foamy histiocytes, lymphocytes, and plasma cells. Immunohistochemistry reveals cells positive for CD68 and CD163 and negative for CD1a, with 20% positivity to S-100. There is no standard treatment for ECD, although chemotherapy, radiation, stem cell transplantation, alpha-interferon, anakinra, imatinib and sirolimus have been proposed. The recent discovery of the BRAFV600E mutation in several ECD patients has opened a new area for treatment options. Vemurafenib, an FDA approved BRAF inhibitor for the treatment of patients with metastatic or unresectable melanoma with the V600E mutation, binds to this form of mutated BRAF causing protein inactivation. The use of vemurafenib in patients with ECD has been reported in 3 patients who experienced remission of the disease, and is currently being studied in the U.S. and Europe as monotherapy. Tumor/disease resistance to vemurafenib has occurred in melanoma and other cancers, although it has not been reported in patients with ECD. In this protocol, we propose to clinically evaluate ECD patients with the BRAFV600E mutation and administer combination therapy with dabrafenib, a BRAFV600E inhibitor, and trametinib, an inhibitor of MEK, downstream of BRAF. Screening for possible contraindications will be made prior to the administration of the first dose. With this trial, we will determine the safety, tolerability, and efficacy of dabrafenib and trametinib in patients with ECD who harbor the BRAFV600E mutation. Dabrafenib 150mg will be given twice daily p.o.; trametinib 2mg will be given once daily p.o. Patients will be seen 1 week, 1 month, 2 months, 4 months, and 6 months, 8 months, 10 months and 12 months to complete a one-year trial.

The rare histiocytic disorders (RHDs) are characterized by the infiltration of one or more organs by non-LCH histiocytes. They can range from localized disease that resolves spontaneously, to progressive disseminated forms that can be sometimes life-threatening. Since they are extremely rare, there is limited understanding of their causes and best treatment options. Physicians, patients and parents of children with RHDs frequently consult members of the Histiocyte Society regarding the best management of these disorders. Very often, no specific recommendation can be made due to the lack of prospective outcome data, or even large retrospective case series. The creation of an international rare histiocytic disorders registry (IRHDR) could facilitate a uniform diagnosis of the RHDs, as well as the collection and analysis of the clinical, epidemiological, treatment and survival data of patients with RHD. The registry may also lead to future therapeutic recommendations, provide a framework for future clinical trials and create excellent research opportunities.

This phase II trial studies the side effects and how well dabrafenib and trametinib work in treating patients with Erdheim Chester disease that have BRAF V600 gene mutations. Dabrafenib and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Background: - Erdheim Chester Disease (ECD) is a very rare disease in which abnormal white blood cells start growing and affect the bones, kidneys, skin, and brain. ECD can cause severe lung disease, kidney failure, heart disease, and other complications that lead to death. Because ECD is a rare disease, found mostly in men over 40 years of age, there is no standard treatment for it. More information is needed to find out what genes can cause ECD and how best to treat it. Objectives: - To collect study samples and medical information on people with Erdheim Chester Disease. Eligibility: - Individuals 2 to 80 year of age who have been diagnosed with Erdheim Chester Disease. Design: Participants will be screened with a physical exam and medical history. Participants will have a study visit to provide samples for study, including blood, urine, and skin tissue samples. Participants will also have lung, heart, and muscle function tests; imaging studies of the brain, chest, and whole body; a treadmill running stress test; an eye exam; and other tests as needed by the study doctors. Participants will be asked to return for a similar set of tests every 2 years, and to remain in contact for possible treatment options.

The primary objective of this study is to establish the natural history of Farber disease (acid ceramidase deficiency) through the collection and analysis of retrospective and prospective data on patients diagnosed with Farber disease. All patients diagnosed with Farber disease are eligible, including both those who have and have not undergone hematopoietic stem cell transplantation (HSCT). Additionally, data and records from deceased patients will provide valuable retrospective data for this study. The secondary objective of the study is to establish a set of clinical data, laboratory data (biomarkers), and functional data potentially useful for: Assessing the efficacy of HSCT and the efficacy of potential future therapies (for example with RVT-801, recombinant human acid ceramidase) in Farber disease Characterizing changes in symptoms of patients over time Characterizing distinct groups (phenotypes) within the patient population Documenting the disease histories of individual patients to serve as intra-subject control data for those who may enroll in any future clinical studies with therapies for Farber disease The exploratory objectives of the study are: To explore the relationship between patient disease activity or phenotype and specific ceramide levels or specific immunologic markers (cytokines/chemokines) in blood To evaluate a standardized tool, the Farber Disease Natural History Instrument (FDNI), to be used for the collection of patient history information, data from clinical, laboratory, genetic, and functional studies, and data from review of medical records

The main purpose of this study is to discover how 18F-cholineFCH distributes in the body, and see if it can distinguish active histiocytes (tumor) from inflammatory (non- tumor) cells. This tracer has the potential to give the investigators' team more information when trying to identify the tumor cells that are most important to collect with biopsy. In addition, the study will measure levels of 18F-cholineFCH in the biopsy tissue.

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis. Diagnosis of ECD is based on clinical symptoms, imaging and histology with infiltration of tissues by foamy CD68 positive CD1a negative histiocytes. Because half of the ECD patients carry a BRAFV600E mutation, we recently proposed vemurafenib, an inhibitor of mutant BRAF, as a possible targeted therapy. We have treated more than10 patients with refractory ECD with life-threatening manifestations associated with the BRAFV600E mutation and observed a short and long term efficacy. However, vemurafenib may have several side effects and long term administration of this drug has not been evaluated. In other diseases such as melanoma, duration of administration is usually shorter, due to bad prognosis of the disease and progression despite treatment. As in long-term follow-up, ECD patients with vemurafenib seem to have a stable disease, we want to evaluate the possibility of treatment interruption as this is what we do in our current practice. Other BRAF inhibitors, such as dabrafenib, have recently been proposed for treating BRAF mutated histiocytoses. Other BRAF inhibitor interruption treatment should also be prospectively evaluated.

Development of a new mass spectrometry-based biomarker for the early and sensitive diagnosis of Farber disease from the blood