The purpose of this Phase II clinical trial is to establish the safety and effectiveness of trametinib, a targeted therapy, for the treatment of newly or recently diagnosed Langerhans Cell Histiocytosis (LCH) among pediatric patients.
Patients with newly diagnosed Langerhans cell histiocytosis (LCH) OR
Patients with relapsed or refractory disease OR
Patients with newly diagnosed or relapsed/refractory disease who are receiving the liquid formula of trametinib OR
Patients who have been receiving trametinib as a treatment for LCH since January 1, 2020 may be included in the observational chart review to track long-term follow-up. Eligibility for chart review cohort will include receiving trametinib as treatment.
CNS-risk/special site includes: Sphenoid, Mastoid, Orbital, zygomatic, ethmoid, maxillary, or temporal bones, the cranial fossa, pituitary gland or neurodegenerative disease, odontoid peg, vertebral lesion with intraspinal soft tissue extension
Functionally critical: A single lesion not described above which may cause "functionally critical anatomic abnormality" wherein attempts at local therapy would cause unacceptable morbidity. This can be at the discretion of the Principal Investigator.
I103_K104del
E102_I103del
Parallel
Trametinib
DrugParticipants will be given trametinib as a single agent once a day dosing, with a maximum dose of 2kg. Participants who are able to swallow pills will be given oral tablets. Participants unable to swallow pills will be dispensed the liquid formula concentrate at 0.05mg/mL with dosing of 0.015mg/kg.
Time to Progression (TTP)
TTP defined for each participant as the period of time from start of treatment to the manifestation of objective progression, but excluding occurrences of death.
Progression-free Survival (PFS)
PFS defined for each participant as the time from start of treatment to disease progression (recurrence) or death by any cause in the absence of progression.
Overall Survival (OS)
OS defined for each participant as the time from the date of first administration until the date of death from any cause. Participants not having an event at the time of analysis will be censored at the date they were last known to be alive.
Response Rate
The response rate will be defined as the percentage of patients with Complete Response (the disappearance of all signs of LCH in response to treatment), Stable Disease (neither increasing nor decreasing in extent or severity), Partial Response (at least a 30% decrease in the signs of LCH), and Progressive Disease (at least a 20 percent growth in the signs of LCH since the beginning of treatment).
Blood HistioTrak Levels in Participants with BRAF V600E Mutations
The HistioTrak test is a highly sensitive droplet digital PCR (ddPCR)-based molecular assay designed to measure MRD in patients with BRAF V600E-driven histiocytic and other neoplasms.
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