ClinicalTrials.gov record NCT06582745
Targeted Approach to Langerhans Cell Histiocytosis (LCH) Using MEK Inhibitor, Trametinib
Targeted Approach to Langerhans Cell Histiocytosis (LCH) Using MEK Inhibitor, Trametinib
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
A Phase II study testing the drug trametinib in children and young people with newly diagnosed or relapsed Langerhans cell histiocytosis (LCH). Participants receive daily trametinib and are followed over time; the study also includes an observational chart-review group for people treated with trametinib since January 1, 2020. The trial will track disease outcomes and side effects and use tumor and blood genomic testing.
What it is studying. This study is testing the safety and effectiveness of trametinib given daily to pediatric patients with newly diagnosed or relapsed LCH. Investigators will track adverse events and disease outcomes over time and will evaluate genomic testing (liquid, tumor, and tumor-match next-generation sequencing) as part of assessing disease and response.
What the researchers hope to learn. Establish the safety and effectiveness of trametinib for newly diagnosed or relapsed pediatric LCH. Measure clinical outcomes including time to progression, progression-free survival, overall survival, and response rates. Assess adverse events and toxicities related to trametinib. Evaluate the use and performance of genomic testing (including liquid and tumor-based NGS) and MRD measurement (HistioTrak) in LCH.
What this study is about
The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.
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.
Interventions being studied
Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.
- Drug
- Trametinib
Eligibility
The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.
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.
Study description and what participation involves
The study's detailed description, as published on ClinicalTrials.gov.
Show the detailed description from the registry
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.
AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
If assigned to treatment, participants take trametinib once daily in 28-day cycles (tablets if able to swallow, a liquid concentrate option is available for those who cannot). Treatment is planned for a minimum of two years, with participant follow-up for four years after that two-year period; continuing treatment beyond two years is possible if agreed with the treating physician. Study procedures include confirmation of biopsy diagnosis (if not already done), heart checks (EKG/ECHO), routine blood tests, imaging scans (CT/MRI/PET) to assess disease, and genomic testing using blood and tumor samples. An observational chart-review option tracks people who have been on trametinib since Jan 1, 2020 to follow long-term outcomes; all participants will be monitored for side effects and must meet contraception and consent requirements.
How the study is structured. Open-label, non-randomized Phase II treatment trial with two parallel groups: a prospective treatment arm where participants receive trametinib in 28-day cycles (daily dosing, maximum 2 mg; a liquid formula is available for those who cannot swallow tablets), and an observation-only chart-review arm for patients who have been receiving trametinib since January 1, 2020. Participants in the treatment arm are expected to be treated for a minimum of two years and followed afterward; follow-up and testing include clinical assessments and genomic analyses.
Questions you could ask
These questions are suggestions for a conversation with the study team or your own clinician, not advice.
- The listed sites are in United States. Is any of them reachable for me, and does the study help with travel?
- Which of the eligibility criteria would need to be checked with tests before I could join?
More on Langerhans cell histiocytosis
Important dates
- Study start
- Jun 24, 2024
- Primary completion
- June 2039 (estimated)
- Study completion
- December 2039 (estimated)
- Target enrollment
- 75 participants (estimated)
- Last updated on registry
- Apr 7, 2026
- Data verified
- Oct 10, 2026
Sponsor and research team
The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.
- Lead sponsor
- Cook Children's Health Care System
Central study contact
If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.
- Megan Gibbs, BSN, RN 📞 (682) 885-2116 ✉ megan.gibbs@cookchildrens.org
- Angelica Gonzalez, PhD 📞 (682) 3033120 ✉ angelica.gonzalez@cookchildrens.org
Participating sites (1)
- Cook Children's Health Care SystemRecruiting
Fort Worth, Texas, 76104 · United States
- Megan Gibbs, BSN, RN · 682-885-2116 · Megan.Gibbs@cookchildrens.org
- Anish Ray, MD
Terms used on this page · explanations by MedicalUpdates.ai
- relapsed or refractory
- A condition that has not responded to a treatment. 'Relapsed' means it responded and then came back; 'refractory' means it did not respond in the first place.
- observational
- A study in which researchers do not assign participants to a treatment or other intervention. They observe or measure what happens, which may include study visits, tests, questionnaires or a review of medical records.
- long-term follow-up
- Observation that continues for years after the study treatment, often required for gene and cell therapies.
- cohort
- A group of people who share a characteristic, such as a diagnosis, and are studied together. 'Prospective' means they are followed forward from enrolment; 'retrospective' means existing records are reviewed.
- biopsy
- Removal of a small piece of tissue so it can be examined under a microscope. 'Biopsy-proven' or 'histologically confirmed' means the diagnosis was confirmed by examining tissue under a microscope.
- Echocardiogram
- An ultrasound scan of the heart. A transesophageal echocardiogram is done through a probe passed into the food pipe for a closer view.
- Electrocardiogram
- A recording of the heart's electrical activity. QTc is one measurement from it; some drugs are avoided if it is prolonged.
- Performance status
- A scale from 0 to 5 that describes how a person's condition affects daily activity. 0 means fully active; 1 means restricted in strenuous activity; 2 means able to self-care but unable to work; higher numbers mean more limitation.
- Karnofsky
- A scale from 100 (no complaints) down to 0 that describes how well a person can carry out daily activities. Studies often require a minimum score.
- Absolute Neutrophil count
- The number of neutrophils, a type of white blood cell that fights infection, in a blood sample. Studies often require it to be above a set level.
- ULN
- The highest value of a blood test that a laboratory considers normal. Criteria such as '≤ 3 × ULN' mean the result must be no more than three times that value.
- Women of childbearing potential
- Studies often ask participants who could become pregnant, or could father a child, to use contraception during the study and for a period afterwards, because the effect of the treatment on a pregnancy is unknown.
- Principal Investigator
- The doctor or scientist responsible for running the study at a site or overall.
- legally authorized representative
- A person who is legally allowed to make decisions, including consent to research, on behalf of someone who cannot consent for themselves.
- written informed consent
- The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
- Inclusion Criteria
- The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
- Exclusion Criteria
- The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
- CT
- An X-ray scan that builds detailed cross-section images of the body. 'High-resolution' CT (HRCT) is used to look closely at the lungs.
- MRI
- A scan that uses magnets and radio waves, not X-rays, to make detailed pictures of the inside of the body. Some implants and metal objects mean a person cannot have one.
- PET
- A scan in which a small amount of a radioactive tracer is injected so that activity in tissues can be seen. Often combined with a CT or MRI scan.
- relapsed
- A condition that improved with treatment and has since returned or worsened.
- adverse events
- Any unwanted medical problem that happens during a study, whether or not it was caused by the treatment. A 'serious' adverse event is one that meets specific criteria, such as causing death, being life-threatening, requiring or prolonging hospital admission, causing significant disability, or another medically important outcome.
The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.
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