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

NCT06582745 | Recruiting Phase 2 FDA Drug

• 1 other identifier: 2023-058
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Langerhans Cell Histiocytosis

Keywords

LCH; MEK inhibitor; Targeted therapy

Outcome Measures

Primary Outcomes (3)

• 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.

  Up to six years

• 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.

  Up to six years

• 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.

  Up to six years

Secondary Outcomes (2)

• Response Rate

  Up to six years

• Blood HistioTrak Levels in Participants with BRAF V600E Mutations

  Up to six years

Study Arms (2)

Prospective Treatment

EXPERIMENTAL

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.

Drug: Trametinib

Observation Only

NO INTERVENTION

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.

Interventions

Trametinib DRUG

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.

Also known as: Mekinist

Prospective Treatment

Eligibility Criteria

• Age: 1 Year - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosis/disease status:
• 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

You may not qualify if:

• Patients diagnosed with Low-Risk True Skin Only or a Single Bone lesion that does not require treatment and will only be observed will not be eligible, with the exception of CNS-risk lesions/special site disease or functionally critical lesions:
• 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.

Sponsors & Collaborators

• Cook Children's Health Care System: lead

Study Sites (1)

Cook Children's Health Care System

Fort Worth, Texas, 76104, United States

RECRUITING

Related Publications (19)

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MeSH Terms

Conditions

Histiocytosis, Langerhans-Cell

Interventions

trametinib

Condition Hierarchy (Ancestors)

Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Anish Ray, MD

  Cook Children's Health Care System

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Megan Gibbs, BSN, RN

CONTACT

(682) 885-2116; megan.gibbs@cookchildrens.org

Alice Hoeft

CONTACT

(682) 885-8086; alice.hoeft@cookchildrens.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2024
• First Posted: September 3, 2024
• Study Start: June 24, 2024
• Primary Completion (Estimated): June 1, 2039
• Study Completion (Estimated): December 1, 2039
• Last Updated: August 27, 2025

Record last verified: 2024-12

Locations

US (1)