Modified LCH-III chemotherapy with or without luvometinib for multisystem pediatric LCH

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

This trial will test whether adding luvometinib to a modified LCH-III chemotherapy plan helps children (ages 0–18) with multisystem Langerhans cell histiocytosis stay in remission longer.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 0 Years to 18 Years
• Sex: All
• Sponsor: West China Second University Hospital (Academic / other)
• Drugs / interventions: trametinib, luvometinib, chemotherapy, prednisone
• Locations: 11 sites (Chengdu and 10 other locations)
• Trial ID: NCT07431060 on ClinicalTrials.gov

What this trial studies

This randomized, multicenter interventional trial will assign children with newly diagnosed multisystem LCH to receive a modified LCH-III chemotherapy backbone with or without the MAPK pathway inhibitor luvometinib. Treatment includes prednisone, vincristine, and mercaptopurine with scheduled dosing per the modified regimen, and luvometinib is given concurrently in the experimental arm. Investigators will compare response, relapse rates, and safety between the two arms over defined follow-up periods. The rationale is that MAPK inhibition may sensitize LCH cells to chemotherapy and reduce relapse by altering the tumor immune environment.

Who should consider this trial

Good fit: Children aged 0–18 with pathologically confirmed multisystem LCH (CD1a and/or CD207 positive) who have not received prior LCH-directed therapy and whose parents/guardians can provide informed consent are ideal candidates.

Not a fit: Children with single-system or low-risk LCH, those with significant excluded comorbidities, prior second malignancy, or who cannot safely receive the protocol drugs (for example due to QTc prolongation) are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, adding luvometinib could reduce relapse rates and increase durable remission in children with multisystem high-risk LCH.

How similar studies have performed: Small studies and real-world series combining MAPK inhibitors with chemotherapy have reported high response rates and lower relapse in difficult-to-treat LCH, but large randomized evidence is still limited.

Eligibility criteria

Inclusion Criteria:

1. Children aged 0-18 years, of either sex.
2. 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.
3. Multisystem involvement of LCH, as determined by clinical and imaging evaluation.
4. 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:

1. 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.
2. History of a second (secondary) malignancy.
3. QTcF interval \> 0.47 seconds on electrocardiogram performed prior to enrollment.
4. 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.
5. 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.
6. Refusal or inability to provide written informed consent (or assent, as applicable).

Where this trial is running

Chengdu and 10 other locations

• West China Second Hospital, Sichuan University — Chengdu, China (Recruiting)
• Affiliated Hospital of Guizhou Medical University — Guiyang, China (Recruiting)
• Anhui Provincial Children's Hospital — Hefei, China (Recruiting)
• The Second Affiliated Hospital of Anhui Medical University — Hefei, China (Recruiting)
• Jiangxi Provincial Children's Hospital — Jiangxi, China (Recruiting)
• Kunming Children's Hospital — Kunming, China (Recruiting)
• The Second Affiliated Hospital of Guangxi Medical University — Nanning, China (Recruiting)
• The First Affiliated Hospital of Xinjiang Medical University — Ürümqi, China (Recruiting)
• Xi'an Children's Hospital — Xi'an, China (Recruiting)
• Xi'an Northwest Women's and Children's Hospital — Xi'an, China (Recruiting)
• Zunyi Medical University Affiliated Hospital, Guizhou Provincial Children's Hospital — Zunyi, China (Recruiting)

Study contacts

• Study coordinator: Xue Tang

Conditions Langerhans Cell Histiocytosis; Luvometinib