Status:
RECRUITING
Targeted Approach to Langerhans Cell Histiocytosis (LCH) Using MEK Inhibitor, Trametinib
Lead Sponsor:
Cook Children's Health Care System
Conditions:
Langerhans Cell Histiocytosis
Eligibility:
All Genders
1-30 years
Phase:
PHASE2
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 Histiocytos...
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 ...
Eligibility Criteria
Inclusion
- 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
- 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.
Key Trial Info
Start Date :
June 24 2024
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
December 1 2039
Estimated Enrollment :
75 Patients enrolled
Trial Details
Trial ID
NCT06582745
Start Date
June 24 2024
End Date
December 1 2039
Last Update
August 27 2025
Active Locations (1)
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1
Cook Children's Health Care System
Fort Worth, Texas, United States, 76104