Targeted treatment for Langerhans Cell Histiocytosis using trametinib

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This Phase II clinical trial aims to evaluate the safety and effectiveness of trametinib, a targeted therapy, for pediatric patients newly diagnosed or relapsed with Langerhans Cell Histiocytosis (LCH). The study will involve a biopsy for diagnosis and utilize imaging techniques like CT, MRI, and PET to assess disease extent. The goal is to establish trametinib as a new treatment option, moving away from traditional cytotoxic chemotherapy that often leads to serious side effects and relapses.

Why it matters

Who can join: the full rules

Inclusion Criteria:

* 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
  * 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:

* 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.

Where it's running

• Cook Children's Health Care System
  Fort Worth, Texas, United States Recruiting

Study contacts

• Principal investigator: Anish Ray, MD — Cook Children's Health Care System
• Study coordinator: Megan Gibbs, BSN, RN
• Email: megan.gibbs@cookchildrens.org
• Phone: (682) 885-2116

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

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• Gefitinib, trametinib, disulfiram, and sunitinib added to standard chemotherapy for metastatic osteosarcoma

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• Dabrafenib and trametinib for rare cancers with BRAF V600 mutations

  This arm tests whether dabrafenib and trametinib can help adults, children, and teens with cancers that have a BRAF V600 mutation.

  Recruiting at 15 sites Phase 2/3 Cancer Research UK · Belfast and 26 other locations · NCT07440290

• Low-dose cytarabine combined with thalidomide for adults with newly diagnosed LCH

  This trial tests whether combining low-dose cytarabine with thalidomide is safe and effective for adults newly diagnosed with multisystem or multifocal Langerhans cell histiocytosis.

  Recruiting Phase 2 Cancer Institute and Hospital, Chinese Academy of Medical Sciences · Beijing · NCT07187193

• Dabrafenib and trametinib dose-reduction for BRAF V600 low-grade glioma

  This trial tries to see if stopping or slowly lowering dabrafenib and trametinib after about 12–24 months works for people with BRAF V600–mutant low-grade glioma.

  Recruiting at 12 sites Phase 2 University of California, San Francisco · Birmingham, Alabama and 11 other locations · NCT07110246

• Dabrafenib or Trametinib plus Clofarabine for high-risk or relapsed pediatric Langerhans cell histiocytosis

  This treatment will test whether adding a MAPK inhibitor (dabrafenib or trametinib) to the chemotherapy drug clofarabine helps children and teens (0–18) with high-risk, recurrent, or refractory Langerhans cell histiocytosis.

  Recruiting Phase 2 West China Second University Hospital · Chengdu, Sichuan · NCT07022834

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.