Langerhans Cell Histiocytosis (LCH)
Conditions
Brief summary
Langerhans cell histiocytosis (LCH) is the most common type of histiocytic disorder in children, affecting about 2.6 to 8.9 out of every million kids each year. It can look very different from one child to another-some cases get better on their own-but when it affects special bones (like the base of the skull, temporal bone, eye socket, or spine) or when there are multiple bone lesions in one system, children often face a higher risk of long-term complications and the disease coming back.Current guidelines in China and around the world recommend treating these children with whole-body therapy, usually a chemotherapy combination of vinblastine and prednisone. However, even with longer treatment courses, about 27.6% of children with multiple bone lesions still have the disease return, and less than 70% stay free of events after 5 years. Some even develop lasting nerve system problems. In recent years, researchers discovered that nearly all children with LCH have overactive MAPK signaling pathways in their cells. This discovery opened the door to using MAPK inhibitors as a new treatment. Studies have shown that these drugs work well and are safe for children with relapsed or hard-to-treat LCH. Even better, in some kids with single-system bone disease, the disease did not come back after stopping the drug-suggesting it might even cure certain cases. Luvometinib (also called FCN-159), a new MAPK inhibitor developed by Fosun Pharma in Shanghai, was approved in 2025 for treating adult LCH. A Phase II clinical study showed very encouraging results: 82.8% of patients saw their disease improve or disappear, and 74.4% stayed free of progression after 12 months. The drug was well tolerated, with side effects that were mild and manageable-no serious problems forced anyone to stop treatment.Compared to traditional chemotherapy, luvometinib has fewer and milder side effects, does not weaken the immune system, and lets children continue normal daily life and school. It is a simple oral pill taken once a day, so there's no need for intravenous lines or hospital stays, making treatment much easier and improving quality of life for both the child and the family.
Interventions
DRUGLuvometinib
5 mg/m² orally once daily for 1 year
Sponsors
West China Second University Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
0 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
1. Children aged 0-18 years, both sexes. 2. Pathologically confirmed diagnosis of LCH (CD1a+ and/or CD207+), with no prior treatment specific to LCH. 3. Patients assessed as having single-system multifocal bone involvement, single-site bone involvement at central nervous system risk sites (central nervous system risk sites include craniofacial region \[excluding parietal, occipital, and frontal bones\], orbital, ear, and oral regions), or single-site vertebral bone involvement with intraspinal space-occupying lesion compressing the spinal cord. 4. Signed informed consent, willing to receive treatment according to this protocol and undergo follow-up.
Exclusion criteria
1. Patients with other underlying diseases, such as primary immunodeficiency, heart failure, renal insufficiency, hepatitis virus infection, HIV infection, post-organ transplantation, etc. 2. Secondary malignancy. 3. QTcF \> 0.47 seconds on electrocardiogram prior to enrollment. 4. Ophthalmologic screening prior to enrollment reveals retinal vein occlusion, retinal pigment epithelial detachment, or other ocular diseases. 5. Patients with LCH carrying category 3 MEK mutations, specifically the following mutation sites: L98\_I103del, L98\_K104del, P105\_A106del, P105\_I107delinsL, L101\_I103delinsF, E102\_I103delinsF, E102\_I103del, E102\_I103delinsV, E102\_I103delinsVN, E102\_K104delinsQ, I103\_A106del. 6. Refusal to sign the informed consent form.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Event-free survival rate | 2-year |
Secondary
| Measure | Time frame |
|---|---|
| Objective response rate | 1 month and 3 month |
| Overall survival rate | 2-year |
| Safety of luvometinib | 1-year |
| Quality of life assessment in children | Before therapy，1month，3months，6months， 12months |
| Survey on satisfaction with drug treatment in children | Before therapy，1month，3months，6months， 12months |
Countries
China
Contacts
CONTACTXue Tang
Outcome results
None listed