Long-term Outcome After Vemurafenib / BRAF Inhibitors Interruption in Erdheim-chester Disease

NCT02089724 | Unknown DMC

• 1 other identifier: medint001
• Study Type: observational
• Target: 20
• Locations: 2 countries
• Sites: 2

Brief Summary

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.

Conditions

Erdheim-Chester Disease

Outcome Measures

Primary Outcomes (1)

• PET scan response

  Modification of SUVmax between M0 and M6 will be used as the main evaluation criteria for each lesion. As assessed by PERCIST criteria, patients will be classified as complete metabolic responders (CMR; complete resolution of pathologic 18F-FDG uptake), partial metabolic responders (PMR; reduction of a minimum of 30% in activity of target lesions), stable metabolic disease (SMD; not CMR, PMR, or progressive metabolic disease (PMD; increase of a minimum of 30% in activity of target lesions or presentation of a new lesion). In contrast to the PERCIST suggestions, tumor SUVmax rather than peak SUV will be measured. Target lesion will be defined by the most active lesion on FDG-PET/CT study before treatment and, for each patient, one or two secondary target lesions among the most active lesions will also be studied. Side-by-side image review and analysis will be performed to ascertain that the SUVmax is derived from the same lesions on baseline and follow-up scans

  6 months (M6)

Secondary Outcomes (3)

• Specific organ assessment (cardiac, retroperitoneal, neurological)

  Months 6 and Months 12

• PET scan

  Months 12

• CRp value (mg/liter)

  Months 6 and Months 12

Study Arms (1)

vemurafenib/other BRAF inhibitors

Eligibility Criteria

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

Study Population

Study population description is patients with Erdheim-Chester disease who have been treated with vemurafenib or other BRAF inhibitor

You may qualify if:

• Age superior or equal to 18 years
• Clinical and radiological presentation concordant with ECD
• Presence of histological proof of ECD
• Treatment with vemurafenib or other BRAF inhibitor
• Agreement to participate

You may not qualify if:

• Pregnancy
• 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).

Sponsors & Collaborators

• Groupe Hospitalier Pitie-Salpetriere: lead
• Memorial Sloan Kettering Cancer Center: collaborator

Study Sites (2)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

AP-HP, Groupe Hospitalier Pitié-Salpêtrière

Paris, 75013, France

RECRUITING

Related Publications (3)

• 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.

  PMID: 24532298 BACKGROUND

• 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.

  PMID: 23258922 BACKGROUND

• 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.

  PMID: 22879539 BACKGROUND

MeSH Terms

Conditions

Erdheim-Chester Disease

Condition Hierarchy (Ancestors)

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

Study Officials

• Julien Haroche, MD, PhD

  Groupe Hospitalier Pitié-Salpêtrière

  PRINCIPAL INVESTIGATOR

• Fleur Cohen Aubart, MD, PhD

  Groupe Hospitalier Pitié-Salpêtrière

  STUDY DIRECTOR

• Eli L. Diamond, MD, PhD

  Memorial Sloan Kettering Cancer Center

  STUDY CHAIR

Central Study Contacts

Julien Haroche, MD, PhD

CONTACT

+33 1 42 17 80 37; julien.haroche@psl.aphp.fr

Fleur Cohen Aubart, PD, PhD

CONTACT

+33 1 42 17 82 42; fleur.cohen@psl.aphp.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr Cohen Aubart

Study Record Dates

• First Submitted: March 15, 2014
• First Posted: March 18, 2014
• Study Start: March 1, 2014
• Primary Completion: December 1, 2016
• Study Completion: April 1, 2019
• Last Updated: October 28, 2016

Record last verified: 2016-10

Locations

US (1); FR (1)