Targeted Approach to Langerhans Cell Histiocytosis (LCH) Using MEK Inhibitor, Trametinib
NCT ID: NCT06582745
Last Updated: 2025-08-27
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE2
75 participants
INTERVENTIONAL
2024-06-24
2039-12-31
Brief Summary
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Detailed Description
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This trial is designed to evaluate treatment of newly diagnosed or relapsed LCH patients with targeted therapy (trametinib). The investigators hypothesize that this will help establish a new treatment for these patients who have historically been treated with cytotoxic chemotherapy that can potentially be associated with serious adverse effects as well as relapse which have typically been noted within two years, therefore justifying the rationale to treat for minimum of two years. This clinical trial will provide an opportunity to assess for adverse events and toxicities associated with trametinib for the treatment of LCH among pediatric patients. Additionally, the investigators will critically analyze the effectiveness of genomic cancer testing through the use of liquid, tumor, and tumor-match next-generation sequencing (NGS) in patients with an LCH diagnosis.
Conditions
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Prospective Treatment
Trametinib will be administered in 28-day cycles, given once daily or adjusted as per clinical judgment of the treating physician, with a maximum dosage of 2mg daily. Patients will be followed for 4 years after receiving treatment for two years. Patients may continue on the same treatment beyond two years if they and their treating physicians agree to do so in the best interest of the patient.
Trametinib
Participants 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.
Observation Only
Patients who have been receiving trametinib as a treatment for LCH since January 1, 2020 may be included in an observational chart review to track long-term follow-up.
No interventions assigned to this group
Interventions
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Trametinib
Participants 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.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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.
* Diagnosis confirmed with biopsy prior to start of treatment
* Patient must have adequate cardiac function evident through Echocardiogram (ECHO) and Electrocardiogram (EKG) within 30 days of starting treatment.
* Shortening fraction of ≥ 27% by echocardiogram or
* Ejection fraction of ≥ 50% by gated radionuclide study
* QTC \< 480 msec
* Performance status: Patients must have a performance status corresponding to ECOG scores of 0, 1, or 2. Use Karnofsky ≥ 50% for patients \> 16 years of age and Lansky ≥50% for patients ≤16 years of age.
* Adequate organ and marrow function as defined below:
* Absolute Neutrophil count ≥ 1,500/μL
* Platelets ≥ 100x103/μL
* Total bilirubin ≤ 1.5X ULN for age
* AST/ALT ≤ 2.5 X ULN for age
* Serum creatinine based on age/gender
* Hemoglobin ≥ 8 g/dL
* Patients with bone marrow disease must have hemoglobin ≥ 8 g/dL with transfusion support allowed
* Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 4 months after the last dose. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
* Ability to understand study procedures and to comply with them for the entire length of the study.
Exclusion Criteria
* 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.
* Patients whose genetic testing reveals a class 3 MAP2K1 mutation:
* I103\_K104del
* E102\_I103del
* L98\_K104delinsQ
* L98\_I103del
* I99\_K104del
* Patients who present with jaundice at diagnosis.
* Patients who are pregnant or breastfeeding are not eligible. Women of childbearing potential must receive a negative pregnancy test within 14 days of starting treatment or the patient will not be eligible.
* Patients who are allergic to trametinib
* Current drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
* Inability or unwillingness of patient or parent/legally authorized representative to give written informed consent.
1 Year
30 Years
ALL
No
Sponsors
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Cook Children's Health Care System
OTHER
Responsible Party
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Principal Investigators
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Anish Ray, MD
Role: PRINCIPAL_INVESTIGATOR
Cook Children's Health Care System
Locations
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Cook Children's Health Care System
Fort Worth, Texas, United States
Countries
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Central Contacts
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Facility Contacts
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References
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Stalemark H, Laurencikas E, Karis J, Gavhed D, Fadeel B, Henter JI. Incidence of Langerhans cell histiocytosis in children: a population-based study. Pediatr Blood Cancer. 2008 Jul;51(1):76-81. doi: 10.1002/pbc.21504.
Badalian-Very G, Vergilio JA, Fleming M, Rollins BJ. Pathogenesis of Langerhans cell histiocytosis. Annu Rev Pathol. 2013 Jan 24;8:1-20. doi: 10.1146/annurev-pathol-020712-163959. Epub 2012 Aug 6.
Allen CE, Ladisch S, McClain KL. How I treat Langerhans cell histiocytosis. Blood. 2015 Jul 2;126(1):26-35. doi: 10.1182/blood-2014-12-569301. Epub 2015 Mar 31.
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Other Identifiers
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2023-058
Identifier Type: -
Identifier Source: org_study_id
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