ClinicalTrials.gov record NCT07431060

Modified LCH-III Regimen With or Without Luvometinib for Multisystem Pediatric Langerhans Cell Histiocytosis

Record copied from ClinicalTrials.gov: Oct 10, 2026AI summaries generated: Jul 27, 2026

Modified LCH-III Regimen Versus Modified LCH-III Regimen Combined With Luvometinib in the Treatment of Multisystem Pediatric Langerhans Cell Histiocytosis: A Multicenter, Open-Label, Randomized Controlled Clinical Trial

StatusRecruitingThe study is currently enrolling participants. Only the study team can say whether a particular person can join.
Study typeInterventionalA study in which researchers assign participants to one or more interventions, such as a drug, procedure, device, behavioural programme or other approach, to measure their effects.
AgeUnder 1 month old to 18 years old
SexAll
LocationChina
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.

This randomized, open-label trial assigns children with multisystem LCH to modified LCH-III chemotherapy alone or the same regimen combined with oral luvometinib. The study compares event-free survival, short-term response, and safety between the two groups, with outcomes assessed up to two years. Treatment uses standard LCH-III drugs (prednisone, vincristine, mercaptopurine) and, in the experimental arm, daily oral luvometinib.

What it is studying. The study tests whether adding the oral MEK1/2 inhibitor luvometinib to a modified LCH-III chemotherapy regimen changes 2-year event-free survival, objective response rates at early time points, and the safety profile in children with multisystem LCH.

What the researchers hope to learn. Compare 2-year event-free survival between the chemotherapy-only and combination arms; measure objective response rates at 1 and 3 months; estimate 2-year overall survival; and assess the frequency and severity of treatment-related adverse events and serious adverse events.

What this study is about

The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.

Langerhans cell histiocytosis (LCH) is the most common histiocytic disorder in children, caused by excessive proliferation and accumulation of Langerhans cells (a type of immune cell) in various body tissues. The annual incidence is about 2.6-8.9 cases per million children.Clinical presentation varies widely. Mild (low-risk) cases may resolve spontaneously or cause minimal issues with excellent outcomes. Severe multisystem LCH involves multiple organs, particularly high-risk sites such as liver, spleen, or bone marrow, leading to poorer prognosis and potential life-threatening complications without appropriate treatment.Standard first-line therapy for many children is prednisone (a corticosteroid) plus vinblastine (chemotherapy). Trials like LCH-III show near-100% survival in low-risk disease, but long-term survival drops to ~80% in high-risk cases. Reactivation occurs in ~37% of low-risk patients post-treatment, and ~50% of children eventually develop resistance, resulting in progression or relapse. Treatment failure heightens risks of long-term sequelae, including growth retardation, endocrine dysfunction, and neurological damage, severely impacting quality of life. More than half of LCH cases harbor the BRAF V600E mutation, activating the MAPK pathway abnormally. This has driven development of targeted MAPK inhibitors (e.g., vemurafenib, dabrafenib, trametinib), which demonstrate strong efficacy and acceptable safety (mainly manageable skin rash) in relapsed/refractory pediatric cases, with no reported secondary malignancies to date. These agents provide rapid symptom relief and durable control, though monotherapy often fails to eradicate abnormal cells in multisystem disease, leading to relapse after discontinuation. No MAPK inhibitors were previously approved specifically for LCH. In 2025, luvometinib (developed by Fosun Pharma, China; a selective MEK1/2 inhibitor) received approval in China for adult LCH and histiocytic neoplasms. Adult studies showed ~83% objective response rate and ~74% progression-free at ≥12 months, with mostly mild side effects (skin issues, hypertriglyceridemia) and no discontinuations due to serious toxicity. Laboratory evidence indicates MAPK overactivation confers apoptosis resistance to LCH cells; combining MAPK inhibitors with chemotherapy may enhance cell killing and leverage chemotherapy-induced immune microenvironment changes for better clearance. Small studies and real-world data in refractory LCH support this: combination regimens yielded low relapse rates (especially with prolonged therapy), 100% responses in some pediatric cohorts with sustained remission and no added severe toxicity, and notably lower relapse (20% vs 75% with inhibitor alone) in our center's early experience with LCH-III backbone plus MAPK inhibitor. This multicenter randomized trial will enroll children with multisystem LCH, assigning them to modified standard LCH-III chemotherapy alone or the same regimen combined with luvometinib, to evaluate whether adding this targeted agent improves outcomes.

Interventions being studied

Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.

Drug
  • Prednisone
  • Vincristine
  • Mercaptopurine
  • Luvometinib

Eligibility

The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.

Inclusion criteria

  • Children aged 0-18 years, of either sex.
  • Pathologically confirmed diagnosis of Langerhans cell histiocytosis (LCH) with positive staining for CD1a and/or CD207 (Langerin), and no prior treatment specifically directed against LCH.
  • Multisystem involvement of LCH, as determined by clinical and imaging evaluation.
  • Provision of written informed consent (by parent/legal guardian and, where appropriate, assent from the child), with willingness to comply with the study treatment regimen and follow-up assessments.

Exclusion criteria

  • Presence of any other significant underlying medical condition, including but not limited to primary immunodeficiency disorders, congestive heart failure, renal insufficiency, chronic viral hepatitis, HIV infection, or status post solid organ transplantation.
  • History of a second (secondary) malignancy.
  • QTcF interval > 0.47 seconds on electrocardiogram performed prior to enrollment.
  • Ophthalmologic screening prior to enrollment revealing retinal vein occlusion, retinal pigment epithelial detachment, or other clinically significant ocular abnormalities that, in the opinion of the investigator, contraindicate participation.
  • LCH harboring Class 3 MEK pathway mutations, specifically the following alterations: L98_I103del, L98_K104del, P105_A106del, P105_I107delinsL, L101_I103delinsF, E102_I103delinsF, E102_I103del, E102_I103delinsV, E102_I103delinsVN, E102_K104delinsQ, or I103_A106del.
  • Refusal or inability to provide written informed consent (or assent, as applicable).

Study description and what participation involves

The study's detailed description, as published on ClinicalTrials.gov.

Show the detailed description from the registry

Lab studies show that when the MAPK pathway is overactive, it makes LCH cells harder to kill (more resistant to dying naturally). Combining an MAPK inhibitor with chemotherapy might make the abnormal cells easier to destroy. Chemotherapy also changes the immune environment in the body, which could help clear out the bad cells more completely. Several small studies and real-world experiences have already tested this idea in children and adults with hard-to-treat LCH: One study combined MAPK inhibitors with certain chemotherapy drugs and saw very few relapses, especially when treatment lasted longer. Another study using a similar approach achieved 100% response in a group of children (including some as first treatment), with most staying in remission afterward, and no extra serious side effects from the combination. A Chinese study using prednisone, another chemo drug, plus an MAPK inhibitor showed good results with low relapse after stopping. Early data from our own center found that children who got an MAPK inhibitor together with the standard LCH-III treatment had much lower relapse rates (only 20%) compared to those who got the inhibitor alone (75% relapse). Based on this growing evidence, this study plans to run a large, carefully designed trial at multiple hospitals. It will randomly assign children with multisystem LCH to receive either the improved (modified) version of the standard LCH-III chemotherapy alone, or the same chemotherapy combined with luvometinib. The goal is to compare how well each approach works and to learn more about whether adding this targeted drug to chemotherapy can improve treatment for children with this disease.

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.

Participants are randomly assigned to receive the modified LCH‑III chemotherapy regimen (prednisone, vincristine, mercaptopurine) either alone or combined with daily oral luvometinib. Care involves regular clinic visits with physical exams, blood tests and imaging to monitor disease and side effects; ECG and eye examinations are performed before enrollment; additional tests during treatment are done if indicated. Study treatment and follow-up assessments are recorded over about two years to track response, events (reactivation, second malignancy, or death), and treatment-related adverse events. Parents or legal guardians must sign informed consent, and children provide assent when appropriate.

How the study is structured. Children are randomly assigned to one of two open-label groups: modified LCH-III chemotherapy alone or the same chemotherapy plus daily oral luvometinib. The trial is multicenter, parallel-group, randomized, and unblinded. Participants receive chemotherapy (prednisone, vincristine, mercaptopurine) and those in the experimental arm also take oral luvometinib; outcomes are followed and assessed for up to two years.

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 China. 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

Clinical trials20 trials listed for Langerhans cell histiocytosisEvery trial the registry lists for Langerhans cell histiocytosis, with recruitment status, phase and sites, updated from ClinicalTrials.gov.See all trials →Research updatesWhat changed in Langerhans cell histiocytosis researchLatest monthly update: September 2026. Includes: Adult routine care. New research summarized each month in plain language, with links to every source paper.Read the latest update →

Important dates

Study start
Feb 13, 2026 (estimated)
Primary completion
Dec 31, 2030 (estimated)
Study completion
Dec 31, 2030 (estimated)
Target enrollment
120 participants (estimated)
Last updated on registry
Feb 24, 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
West China Second University Hospital
Principal investigator
Xia Guo, Professor of Pediatrics
West China Second University Hospital

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.

Participating sites (11)

Terms used on this page · explanations by MedicalUpdates.ai

prednisone
Steroid medicines, such as prednisone, that reduce inflammation. Studies often require a stable dose at entry or measure whether the study treatment allows the dose to be reduced.
relapse
A condition that improved with treatment and has since returned or worsened.
relapsed/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.
randomized
Participants are assigned to the study groups by chance, like a coin toss, rather than chosen by the doctor or the participant. This is done so the groups are comparable.
prior treatment
Treatment a person has already had for the condition. A 'line of therapy' is one course of treatment; studies often require, or limit, the number of prior lines.
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.
legal guardian
A person who is legally allowed to make decisions, including consent to research, on behalf of someone who cannot consent for themselves.
assent
A child's or dependent adult's agreement to take part, given alongside the formal consent of a parent or legal representative.
follow-up
The period after treatment or enrolment during which participants are observed or contacted, for example to record side effects or outcomes.
QTcF
A recording of the heart's electrical activity. QTc is one measurement from it; some drugs are avoided if it is prolonged.
enrollment
The number of participants a study plans to include, or has included. 'Estimated' means the planned number; 'actual' means the number who joined.
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.

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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