Targeted treatment for Langerhans Cell Histiocytosis using trametinib
Targeted Approach to Langerhans Cell Histiocytosis (LCH) Using MEK Inhibitor, Trametinib
This study is testing if trametinib, a new targeted therapy, can help children with Langerhans Cell Histiocytosis feel better and avoid the harsh side effects of traditional chemotherapy.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 75 (estimated) |
| Ages | 1 Year to 30 Years |
| Sex | All |
| Sponsor | Cook Children's Health Care System Academic / other |
| Drugs / interventions | trametinib, chemotherapy |
| Locations | 1 site (Fort Worth, Texas) |
| Trial ID | NCT06582745 on ClinicalTrials.gov |
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.
Who should consider this trial
Good fit: Ideal candidates include pediatric patients with newly diagnosed or relapsed LCH confirmed by biopsy.
Not a fit: Patients with other forms of histiocytic disorders or those who do not meet the eligibility criteria may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could provide a safer and more effective option for children suffering from LCH.
How similar studies have performed: While there is ongoing research in targeted therapies for LCH, this specific approach using trametinib is relatively novel.
Eligibility criteria
Show full inclusion / exclusion criteria
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 this trial is running
Fort Worth, Texas
- 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
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.