Long-term Outcome After Vemurafenib / BRAF Inhibitors Interruption in Erdheim-chester Disease
NCT ID: NCT02089724
Last Updated: 2016-10-28
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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UNKNOWN
20 participants
OBSERVATIONAL
2014-03-31
2019-04-30
Brief Summary
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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.
Detailed Description
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Due to the rare nature of the disease (500 cases worldwide have been reported since 1930) no prospective therapeutic trial has been performed. Interferon alpha (IFN alpha), in its standard or pegylated forms, is the first line therapy for ECD. However, long-term IFN alpha treatment can lead to severe side effects. Moreover, some patients with CNS and/or cardiovascular infiltrations, the two lethal organ involvement, develop secondary resistance to high doses of IFN alpha. For refractory patients, anakinra, cladribine, tyrosine kinase inhibitors, or infliximab have been proposed as second line treatments. The optimal second line therapeutic strategy remains however to be defined, mostly because these treatments have been evaluated in only small numbers of patients.
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 10 patients with refractory ECD with life-threatening manifestations associated with the BRAFV600E mutation and observed a short and long term efficacy (median follow-up 9 months).
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.
Conditions
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Study Design
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COHORT
PROSPECTIVE
Study Groups
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vemurafenib/other BRAF inhibitors
No interventions assigned to this group
Eligibility Criteria
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Inclusion Criteria
* Clinical and radiological presentation concordant with ECD
* Presence of histological proof of ECD
* Treatment with vemurafenib or other BRAF inhibitor
* Agreement to participate
Exclusion Criteria
* Patients who exceed the safe weight limit of the PET/CT bed (220 kg) or who cannot fit through the PET/CT bore (diameter 70 cm).
18 Years
ALL
No
Sponsors
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Memorial Sloan Kettering Cancer Center
OTHER
Groupe Hospitalier Pitie-Salpetriere
OTHER
Responsible Party
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Dr Cohen Aubart
Dr Cohen Aubart
Principal Investigators
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Julien Haroche, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Groupe Hospitalier Pitié-Salpêtrière
Fleur Cohen Aubart, MD, PhD
Role: STUDY_DIRECTOR
Groupe Hospitalier Pitié-Salpêtrière
Eli L. Diamond, MD, PhD
Role: STUDY_CHAIR
Memorial Sloan Kettering Cancer Center
Locations
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Memorial Sloan Kettering Cancer Center
New York, New York, United States
AP-HP, Groupe Hospitalier Pitié-Salpêtrière
Paris, , France
Countries
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Central Contacts
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Facility Contacts
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Eli L. Diamond, MD, PhD
Role: primary
Julien Haroche, MD, PhD
Role: primary
Fleur Cohen Aubart, MD, PhD
Role: backup
References
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Haroche J, Arnaud L, Cohen-Aubart F, Hervier B, Charlotte F, Emile JF, Amoura Z. Erdheim-Chester disease. Curr Rheumatol Rep. 2014 Apr;16(4):412. doi: 10.1007/s11926-014-0412-0.
Haroche J, Cohen-Aubart F, Emile JF, Arnaud L, Maksud P, Charlotte F, Cluzel P, Drier A, Hervier B, Benameur N, Besnard S, Donadieu J, Amoura Z. Dramatic efficacy of vemurafenib in both multisystemic and refractory Erdheim-Chester disease and Langerhans cell histiocytosis harboring the BRAF V600E mutation. Blood. 2013 Feb 28;121(9):1495-500. doi: 10.1182/blood-2012-07-446286. Epub 2012 Dec 20.
Haroche J, Charlotte F, Arnaud L, von Deimling A, Helias-Rodzewicz Z, Hervier B, Cohen-Aubart F, Launay D, Lesot A, Mokhtari K, Canioni D, Galmiche L, Rose C, Schmalzing M, Croockewit S, Kambouchner M, Copin MC, Fraitag S, Sahm F, Brousse N, Amoura Z, Donadieu J, Emile JF. High prevalence of BRAF V600E mutations in Erdheim-Chester disease but not in other non-Langerhans cell histiocytoses. Blood. 2012 Sep 27;120(13):2700-3. doi: 10.1182/blood-2012-05-430140. Epub 2012 Aug 9.
Other Identifiers
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medint001
Identifier Type: -
Identifier Source: org_study_id