Erdheim-Chester DiseaseLOVENCT02089724
Long-term Outcome After Vemurafenib / BRAF Inhibitors Interruption in Erdheim-chester Disease
An observational study of Erdheim-Chester Disease, run by Groupe Hospitalier Pitie-Salpetriere at 2 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Erdheim-Chester Disease
- How many people
- 20 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Mar 2014to Apr 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Study population description is patients with Erdheim-Chester disease who have been treated with vemurafenib or other BRAF inhibitor
Who may be able to join
- 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
Who cannot join
- 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).
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United States1 site, 1 recruiting
- Recruiting
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Eli L. Diamond, MD, PhD, diamonel@mskcc.org
Eli L. Diamond, MD, PhD
France1 site, 1 recruiting
- Recruiting
AP-HP, Groupe Hospitalier Pitié-Salpêtrière
Paris, 75013
Julien Haroche, MD, PhD, +33 1 42 17 80 37, julien.haroche@psl.aphp.fr
Fleur Cohen Aubart, MD, PhD, +33 1 42 17 82 42, fleur.cohen@psl.aphp.fr
About this study
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.
Read more
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.
Read the detailed description
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. The clinical course mainly depends on the extent and distribution of the disease, and ranges from asymptomatic bone lesions to life-threatening manifestations. The overall mortality remains high (22% of the 100 ECD patients seen at our institution in August 2013).
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
- Erdheim-Chester Disease
- Medical subject headings
- Erdheim-Chester Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| vemurafenib/other BRAF inhibitors | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 6 months (M6)
Secondary outcomes (3)
Specific organ assessment (cardiac, retroperitoneal, neurological)
Measured: Months 6 and Months 12
PET scan
Measured: Months 12
CRp value (mg/liter)
Measured: Months 6 and Months 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2014 (estimated)
- Study startMar 2014
- Primary completionDec 2016 (estimated)
- Study completionApr 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Erdheim-Chester DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Groupe Hospitalier Pitie-Salpetriere
- Sponsor type
- University, hospital or other
- Collaborators
- Memorial Sloan Kettering Cancer Center
- Responsible party
- Principal investigator, Dr Cohen Aubart, Groupe Hospitalier Pitie-Salpetriere
- Investigators
- Julien Haroche, MD, PhD, Principal investigator, Groupe Hospitalier Pitie-SalpetriereFleur Cohen Aubart, MD, PhD, Study director, Groupe Hospitalier Pitie-SalpetriereEli L. Diamond, MD, PhD, Study chair, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02089724
- Sponsor's protocol ID
- medint001
- Acronym
- LOVE
- Status last verified
- Oct 2016
- First submitted
- 15 Mar 2014
- Last updated
- 28 Oct 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 24532298Haroche 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.
PubMed 23258922Haroche 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.
PubMed 22879539
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Long-term Outcome After Vemurafenib / BRAF Inhibitors Interruption in Erdheim-chester Disease
- ClinicalTrials.gov ID
- NCT02089724
- Acronym / sponsor ID
- LOVE / medint001
- Conditions
- Erdheim-Chester Disease
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Groupe Hospitalier Pitie-SalpetriereUniversity, hospital or other
- Collaborators
- Memorial Sloan Kettering Cancer Center
- Study start
- Mar 2014
- Primary completion
- Dec 2016 (estimated)
- Study completion
- Apr 2019 (estimated)
- First posted
- 18 Mar 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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. The clinical course mainly depends on the extent and distribution of the disease, and ranges from asymptomatic bone lesions to life-threatening manifestations. The overall mortality remains high (22% of the 100 ECD patients seen at our institution in August 2013).
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| vemurafenib/other BRAF inhibitors | – | – |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Study population description is patients with Erdheim-Chester disease who have been treated with vemurafenib or other BRAF inhibitor
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (2 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
PET scan response
Time frame: 6 months (M6)
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
3 secondary outcomes
Specific organ assessment (cardiac, retroperitoneal, neurological)
Time frame: Months 6 and Months 12
PET scan
Time frame: Months 12
CRp value (mg/liter)
Time frame: Months 6 and Months 12
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2016.
- Background: PubMed 24532298Haroche 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.
- Background: PubMed 23258922Haroche 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.
- Background: PubMed 22879539Haroche 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Julien Haroche, MD, PhD principal investigator
Groupe Hospitalier Pitie-Salpetriere
Fleur Cohen Aubart, MD, PhD study director
Groupe Hospitalier Pitie-Salpetriere
Eli L. Diamond, MD, PhD study chair
Memorial Sloan Kettering Cancer Center
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Erdheim-Chester Disease, run by Groupe Hospitalier Pitie-Salpetriere at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 28 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Julien Haroche, MD, PhD (+33 1 42 17 80 37, julien.haroche@psl.aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PET scan response (time frame: 6 months (M6)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02089724, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2016.