NCT06582745

Targeted Approach to Langerhans Cell Histiocytosis (LCH) Using MEK Inhibitor, Trametinib

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 75 (estimated)
• Sponsor: Cook Children's Health Care System · Academic / Other
• Sex: All
• Age: 1 Year – 30 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

Langerhans cell histiocytosis (LCH) is a rare histiocytic disease derived from the mononuclear phagocytic system, affecting between 2 and 10 cases per one million children under 15 years. Controversy exists as to whether it is a true malignancy or a cancer-like disease, given that the BRAFV600E mutation frequently found in LCH has been found in several cancers as well as in benign nevi. Regardless, among histiocytic disorders, LCH is well-known to result from clonal proliferation of immature cells that can affect a single organ (single system LCH) which may be unifocal or multifocal; or LCH may involve multiple organs which may be limited or widespread. Notably, involvement of specific organs such as the liver, spleen, and bone marrow is typically considered high risk. A biopsy is a critical element for diagnosis as histiocytes with surface expression of CD207 (langerin) and CD1a are a defining characteristic of LCH. In addition to a biopsy of either skin lesion, lymph node, or tumor, standard imaging such as CT, MRI, and PET will be used to assess the extent of disease. 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

• Langerhans Cell Histiocytosis

Interventions

Type	Name	Description
DRUG	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.

Timeline

• Start date: 2024-06-24
• Primary completion: 2039-06-01
• Completion: 2039-12-01
• First posted: 2024-09-03
• Last updated: 2026-04-07

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study