Long-term Outcome After Vemurafenib / BRAF Inhibitors Interruption in Erdheim-chester Disease
| Status: | Recruiting |
|---|---|
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 8/12/2016 |
| Start Date: | March 2014 |
| End Date: | April 2019 |
| Contact: | Julien Haroche, MD, PhD |
| Email: | julien.haroche@psl.aphp.fr |
| Phone: | +33 1 42 17 80 37 |
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.
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.
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.
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.
Inclusion Criteria:
- 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 for at least 6 months
- Agreement to participate
Exclusion Criteria:
- 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).
We found this trial at
2
sites
1275 York Ave
New York, New York 10021
New York, New York 10021
(212) 639-2000
Principal Investigator: Eli L. Diamond, MD, PhD
Memorial Sloan Kettering Cancer Center Memorial Sloan Kettering Cancer Center — the world's oldest and...
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Paris, 75013
Principal Investigator: Julien Haroche, MD, PhD
Phone: +33 1 42 17 80 37
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