Langerhans Cell Histiocytosis (LCH)NCT07431060
Modified LCH-III Regimen With or Without Luvometinib for Multisystem Pediatric Langerhans Cell Histiocytosis
A study testing Prednisone, Vincristine and Mercaptopurine in people with Langerhans Cell Histiocytosis (LCH), run by West China Second University Hospital at 11 sites in China.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 0 to 18 years
- Conditions the study is for
- Langerhans Cell Histiocytosis (LCH)
- What is being tested?
- Prednisone, Vincristine and Mercaptopurine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 11 sitesChina
- Study dates
- 13 Feb 2026to 31 Dec 2030
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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).
Trial locations and contacts
11 sites in 1 country. Contact the study team or a site near you to ask about taking part.
11 sites in 1 country
China11 sites, 11 recruiting
- Recruiting
West China Second Hospital, Sichuan University
Chengdu
XIa Guo, 86+1818609112, guoxkl@163.com
- Recruiting
Affiliated Hospital of Guizhou Medical University
Guiyang
Xiao Yan Yang, 86+18786635712, 469389553@qq.com
- Recruiting
Anhui Provincial Children's Hospital
Hefei
Hong Jun Liu, 86+13515657759, 13515657759@126.com
- Recruiting
The Second Affiliated Hospital of Anhui Medical University
Hefei
Jin Hua Chu, 86+15805602655, 997222161@qq.com
- Recruiting
Jiangxi Provincial Children's Hospital
Jiangxi
Chong Jun Wu, 86+13699560860, wuchongjunmed@163.com
- Recruiting
Kunming Children's Hospital
Kunming
Xin Tian, 86+13668757522, tianxin999@aliyun.com
- Recruiting
The Second Affiliated Hospital of Guangxi Medical University
Nanning
Hong Ying Wei, 86+15977767103, whylhr@qq.com
- Recruiting
The First Affiliated Hospital of Xinjiang Medical University
Ürümqi
MAIMAITI GULIBAHA, 86+13070423745, 156510283@qq.com
- Recruiting
Xi'an Children's Hospital
Xi'an
Hua Wang, 86+18991236496, luoshake0219@163.com
- Recruiting
Xi'an Northwest Women's and Children's Hospital
Xi'an
Hui Liu, 86+15829655607, 15829655607@139.com
- Recruiting
Zunyi Medical University Affiliated Hospital, Guizhou Provincial Children's Hospital
Zunyi
Yan Chen, 86+13985261758, cyz600@163.com
About this study
Official title: 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
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.
Read more
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.
Read the detailed description
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.
- Conditions
- Langerhans Cell Histiocytosis (LCH)
- Being tested
- Prednisone, Vincristine, Mercaptopurine, Luvometinib
- Keywords
- Langerhans Cell Histiocytosis, Luvometinib
- Medical subject headings
- Histiocytosis, Langerhans-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PrednisoneDrug
Corticosteroid administered orally as part of the modified LCH-III regimen
VincristineDrug
Intravenous vinca alkaloid chemotherapy agent used in the modified LCH-III regimen
MercaptopurineDrug
Oral purine analog antimetabolite used in the maintenance phase of therapy for multisystem LCH
LuvometinibDrug
Oral selective MEK1/2 inhibitor added to the experimental arm. Administered daily in combination with modified LCH-III chemotherapy for multisystem Langerhans cell histiocytosis.
| Study group | Role | What they receive |
|---|---|---|
| Modified LCH-III Chemotherapy + Luvometinib (Experimental Arm) | Experimental | Participants receive the same modified LCH-III chemotherapy regimen (prednisone, vinblastine, mercaptopurine) combined with oral luvometinib throughout the treatment period Receives: Drug: Prednisone; Drug: Vincristine; Drug: Mercaptopurine; Drug: Luvometinib |
| Modified LCH-III Chemotherapy Alone (Control Arm) | Active comparator | Participants receive the modified standard LCH-III chemotherapy regimen consisting of prednisone and vincristine. Receives: Drug: Prednisone; Drug: Vincristine; Drug: Mercaptopurine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event-Free survival rate
Event-free survival (EFS) is defined as the time from Day 1 to the first occurrence of any event, including disease reactivation , second primary malignancy, or death from any cause. Events will be assessed by clinical examination, imaging, and laboratory tests. The 2-year EFS rate will be estimated using the Kaplan-Meier method, reported as percentage with 95% confidence interval.
Measured: From Day 1 until the date of first event or last follow-up, assessed up to 2 years.
Secondary outcomes (3)
Objective response rate
Objective response rate (ORR) is defined as the proportion of participants achieving NAD or ADB at the specified time points. Responses will be assessed by clinical evaluation, imaging, and risk organ function (if involved). ORR will be reported separately at 1 month and 3 months as percentage of participants with NAD or ADB (combined), with exact 95% confidence intervals.
Measured: At 1 month and 3 months post-treatment
Overall survival rate
Overall survival (OS) is defined as Day 1 to death from any cause. Participants alive at last follow-up will be censored. The 2-year OS rate will be estimated using the Kaplan-Meier method and reported as percentage with 95% confidence interval.
Measured: From Day1 until date of death from any cause or last follow-up, assessed up to 2 years.
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Safety and tolerability of the combination regimen (luvometinib added to modified LCH-III chemotherapy: prednisone + Vincristine backbone) will be assessed by the number of participants experiencing treatment-related adverse events (TRAEs), and serious adverse events (SAEs). Events will be graded according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Data will be summarized as: Incidence of any TRAE (percentage of participants) , Incidence by maximum grade (e.g., Grade 3-5) ,Incidence of specific events of interest (e.g., skin rash, hypertriglyceridemia, cytopenias) and Rate of treatment discontinuation due to toxicity
Measured: From Day 1 until through study completion, an average of 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2026
- Study start13 Feb 2026 (estimated)
- Primary completion31 Dec 2030 (estimated)
- Study completion31 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for Langerhans Cell Histiocytosis (LCH)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- West China Second University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Xia Guo, West China Second University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07431060
- Sponsor's protocol ID
- WCSH-NCP-MS-LCH-2026
- Status last verified
- Feb 2026
- First submitted
- 13 Feb 2026
- Last updated
- 24 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: IPD might be shared in the future upon approval by the ethics committee and under a data use agreement.
Publications
Lei J, Wang W, Lin D, Zhu C, Jia W, Weng W, Liu X, Ma Y, Wang Z, Yang L, He X, He Y, Li Y. Vemurafenib combined with chemotherapy achieved sustained remission in pediatric LCH: a multi-center observational study. J Cancer Res Clin Oncol. 2024 Jan 17;150(1):12. doi: 10.1007/s00432-023-05551-y.
PubMed 38231288Evseev D, Osipova D, Kalinina I, Raykina E, Ignatova A, Lyudovskikh E, Baidildina D, Popov A, Zhogov V, Semchenkova A, Litvin E, Kotskaya N, Cherniak E, Voronin K, Burtsev E, Bronin G, Vlasova I, Purbueva B, Fink O, Pristanskova E, Dzhukaeva I, Erega E, Novichkova G, Maschan A, Maschan M. Vemurafenib combined with cladribine and cytarabine results in durable remission of pediatric BRAF V600E-positive LCH. Blood Adv. 2023 Sep 26;7(18):5246-5257. doi: 10.1182/bloodadvances.2022009067.
PubMed 37216396Karri V, Lin H, Velazquez J, Batajoo A, Parekh D, Stanton W, Abhyankar H, El-Mallawany NK, Agrusa J, Eckstein O, Gulati N, Schwartz J, Woods-Swafford W, Boyd J, Saha A, Allen CE, McClain KL. Clinical, radiological and molecular responses to combination chemotherapy with MAPK pathway inhibition in relapsed and refractory Langerhans cell histiocytosis. Br J Haematol. 2024 May;204(5):1882-1887. doi: 10.1111/bjh.19380. Epub 2024 Mar 19.
PubMed 38501390Bigenwald C, Le Berichel J, Wilk CM, Chakraborty R, Chen ST, Tabachnikova A, Mancusi R, Abhyankar H, Casanova-Acebes M, Laface I, Akturk G, Jobson J, Karoulia Z, Martin JC, Grout J, Rafiei A, Lin H, Manz MG, Baccarini A, Poulikakos PI, Brown BD, Gnjatic S, Lujambio A, McClain KL, Picarsic J, Allen CE, Merad M. BRAFV600E-induced senescence drives Langerhans cell histiocytosis pathophysiology. Nat Med. 2021 May;27(5):851-861. doi: 10.1038/s41591-021-01304-x. Epub 2021 May 6.
PubMed 33958797Hogstad B, Berres ML, Chakraborty R, Tang J, Bigenwald C, Serasinghe M, Lim KPH, Lin H, Man TK, Remark R, Baxter S, Kana V, Jordan S, Karoulia Z, Kwan WH, Leboeuf M, Brandt E, Salmon H, McClain K, Poulikakos P, Chipuk J, Mulder WJM, Allen CE, Merad M. RAF/MEK/extracellular signal-related kinase pathway suppresses dendritic cell migration and traps dendritic cells in Langerhans cell histiocytosis lesions. J Exp Med. 2018 Jan 2;215(1):319-336. doi: 10.1084/jem.20161881. Epub 2017 Dec 20.
PubMed 29263218Cao XX, Zhu Q, Cai Z, Ma J, Zhou H, Chang L, Zhong LP, Wu ZL, Wang X, Han P, Lin HM, Wei Z, Guo JY, Zheng Y, Li J. Luvometinib in patients with Langerhans cell histiocytosis, Erdheim-Chester disease, and other histiocytic neoplasms: a single-arm, multicentre, phase 2 study. EClinicalMedicine. 2025 Sep 17;88:103486. doi: 10.1016/j.eclinm.2025.103486. eCollection 2025 Oct.
PubMed 41035796Keam SJ. Luvometinib: First Approval. Drugs. 2025 Sep;85(9):1177-1183. doi: 10.1007/s40265-025-02217-6. Epub 2025 Aug 2.
PubMed 40751881Whitlock JA, Geoerger B, Dunkel IJ, Roughton M, Choi J, Osterloh L, Russo M, Hargrave D. Dabrafenib, alone or in combination with trametinib, in BRAF V600-mutated pediatric Langerhans cell histiocytosis. Blood Adv. 2023 Aug 8;7(15):3806-3815. doi: 10.1182/bloodadvances.2022008414.
PubMed 36884302Cournoyer E, Ferrell J, Sharp S, Ray A, Jordan M, Dandoy C, Grimley M, Roy S, Lorsbach R, Merrow AC, Nelson A, Bartlett A, Picarsic J, Kumar A. Dabrafenib and trametinib in Langerhans cell histiocytosis and other histiocytic disorders. Haematologica. 2024 Apr 1;109(4):1137-1148. doi: 10.3324/haematol.2023.283295.
PubMed 37731389Donadieu J, Larabi IA, Tardieu M, Visser J, Hutter C, Sieni E, Kabbara N, Barkaoui M, Miron J, Chalard F, Milne P, Haroche J, Cohen F, Helias-Rodzewicz Z, Simon N, Jehanne M, Kolenova A, Pagnier A, Aladjidi N, Schneider P, Plat G, Lutun A, Sonntagbauer A, Lehrnbecher T, Ferster A, Efremova V, Ahlmann M, Blanc L, Nicholson J, Lambilliote A, Boudiaf H, Lissat A, Svojgr K, Bernard F, Elitzur S, Golan M, Evseev D, Maschan M, Idbaih A, Slater O, Minkov M, Taly V, Collin M, Alvarez JC, Emile JF, Heritier S. Vemurafenib for Refractory Multisystem Langerhans Cell Histiocytosis in Children: An International Observational Study. J Clin Oncol. 2019 Nov 1;37(31):2857-2865. doi: 10.1200/JCO.19.00456. Epub 2019 Sep 12.
PubMed 31513482Haupt R, Nanduri V, Calevo MG, Bernstrand C, Braier JL, Broadbent V, Rey G, McClain KL, Janka-Schaub G, Egeler RM. Permanent consequences in Langerhans cell histiocytosis patients: a pilot study from the Histiocyte Society-Late Effects Study Group. Pediatr Blood Cancer. 2004 May;42(5):438-44. doi: 10.1002/pbc.20021.
PubMed 15049016Parekh D, Lin H, Batajoo A, Peckham-Gregory E, Karri V, Stanton W, Scull B, Fleishmann R, El-Mallawany N, Eckstein OS, Prudowsky ZD, Gulati N, Agrusa JE, Ahmed AZ, Chu R, Dietz MS, Goldman SC, Hogarty MD, Imran H, Intzes S, Kim JM, Kopp LM, Levy CF, Neff P, Pillai PM, Sisk BA, Schiff DE, Trobaugh-Lotrario AD, Walkovich K, McClain KL, Allen CE. Clofarabine monotherapy in aggressive, relapsed and refractory Langerhans cell histiocytosis. Br J Haematol. 2024 May;204(5):1888-1893. doi: 10.1111/bjh.19376. Epub 2024 Mar 19.
PubMed 38501389Lin H, Batajoo A, Peckham-Gregory E, Zinn D, Eckstein OS, El-Mallawany NK, Gulati N, Prudowsky ZD, Scull B, Velazquez J, Abhyankar H, Simko SJ, Vakula D, Fleischmann R, Karri V, Hicks MJ, Fisher KE, Curry CV, Roy A, Schiff D, Heym KM, Scheurer ME, Parsons DW, Merad M, Man TK, McClain KL, Picarsic J, Allen CE. BRAF V600E-positive mononuclear cells in blood at diagnosis portend treatment failure and neurodegeneration in pediatric LCH. Blood. 2025 Jul 10;146(2):206-218. doi: 10.1182/blood.2024026671.
PubMed 40167581Rodriguez-Galindo C, Allen CE. Langerhans cell histiocytosis. Blood. 2020 Apr 16;135(16):1319-1331. doi: 10.1182/blood.2019000934.
PubMed 32106306
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07431060
- Acronym / sponsor ID
- WCSH-NCP-MS-LCH-2026
- Conditions
- Langerhans Cell Histiocytosis (LCH)
- Keywords
- Langerhans Cell Histiocytosis, Luvometinib
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- West China Second University HospitalUniversity, hospital or other
- Study start
- 13 Feb 2026 (estimated)
- Primary completion
- 31 Dec 2030 (estimated)
- Study completion
- 31 Dec 2030 (estimated)
- First posted
- 24 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Modified LCH-III Chemotherapy + Luvometinib (Experimental Arm) | Experimental | Drug: Prednisone, Drug: Vincristine, Drug: Mercaptopurine, Drug: LuvometinibParticipants receive the same modified LCH-III chemotherapy regimen (prednisone, vinblastine, mercaptopurine) combined with oral luvometinib throughout the treatment period |
| Modified LCH-III Chemotherapy Alone (Control Arm) | Active comparator | Drug: Prednisone, Drug: Vincristine, Drug: MercaptopurineParticipants receive the modified standard LCH-III chemotherapy regimen consisting of prednisone and vincristine. |
Who may qualify
- Ages
- 0 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PrednisoneCorticosteroid administered orally as part of the modified LCH-III regimen | Drug | Modified LCH-III Chemotherapy + Luvometinib (Experimental Arm), Modified LCH-III Chemotherapy Alone (Control Arm) |
| VincristineIntravenous vinca alkaloid chemotherapy agent used in the modified LCH-III regimen | Drug | Modified LCH-III Chemotherapy + Luvometinib (Experimental Arm), Modified LCH-III Chemotherapy Alone (Control Arm) |
| MercaptopurineOral purine analog antimetabolite used in the maintenance phase of therapy for multisystem LCH | Drug | Modified LCH-III Chemotherapy + Luvometinib (Experimental Arm), Modified LCH-III Chemotherapy Alone (Control Arm) |
| LuvometinibOral selective MEK1/2 inhibitor added to the experimental arm. Administered daily in combination with modified LCH-III chemotherapy for multisystem Langerhans cell histiocytosis. | Drug | Modified LCH-III Chemotherapy + Luvometinib (Experimental Arm) |
Primary outcome
Event-Free survival rate
Time frame: From Day 1 until the date of first event or last follow-up, assessed up to 2 years.
Event-free survival (EFS) is defined as the time from Day 1 to the first occurrence of any event, including disease reactivation , second primary malignancy, or death from any cause. Events will be assessed by clinical examination, imaging, and laboratory tests. The 2-year EFS rate will be estimated using the Kaplan-Meier method, reported as percentage with 95% confidence interval.
3 secondary outcomes
Objective response rate
Time frame: At 1 month and 3 months post-treatment
Overall survival rate
Time frame: From Day1 until date of death from any cause or last follow-up, assessed up to 2 years.
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time frame: From Day 1 until through study completion, an average of 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2026.
- Results publication: PubMed 38231288Lei J, Wang W, Lin D, Zhu C, Jia W, Weng W, Liu X, Ma Y, Wang Z, Yang L, He X, He Y, Li Y. Vemurafenib combined with chemotherapy achieved sustained remission in pediatric LCH: a multi-center observational study. J Cancer Res Clin Oncol. 2024 Jan 17;150(1):12. doi: 10.1007/s00432-023-05551-y.
- Results publication: PubMed 37216396Evseev D, Osipova D, Kalinina I, Raykina E, Ignatova A, Lyudovskikh E, Baidildina D, Popov A, Zhogov V, Semchenkova A, Litvin E, Kotskaya N, Cherniak E, Voronin K, Burtsev E, Bronin G, Vlasova I, Purbueva B, Fink O, Pristanskova E, Dzhukaeva I, Erega E, Novichkova G, Maschan A, Maschan M. Vemurafenib combined with cladribine and cytarabine results in durable remission of pediatric BRAF V600E-positive LCH. Blood Adv. 2023 Sep 26;7(18):5246-5257. doi: 10.1182/bloodadvances.2022009067.
- Results publication: PubMed 38501390Karri V, Lin H, Velazquez J, Batajoo A, Parekh D, Stanton W, Abhyankar H, El-Mallawany NK, Agrusa J, Eckstein O, Gulati N, Schwartz J, Woods-Swafford W, Boyd J, Saha A, Allen CE, McClain KL. Clinical, radiological and molecular responses to combination chemotherapy with MAPK pathway inhibition in relapsed and refractory Langerhans cell histiocytosis. Br J Haematol. 2024 May;204(5):1882-1887. doi: 10.1111/bjh.19380. Epub 2024 Mar 19.
- Results publication: PubMed 33958797Bigenwald C, Le Berichel J, Wilk CM, Chakraborty R, Chen ST, Tabachnikova A, Mancusi R, Abhyankar H, Casanova-Acebes M, Laface I, Akturk G, Jobson J, Karoulia Z, Martin JC, Grout J, Rafiei A, Lin H, Manz MG, Baccarini A, Poulikakos PI, Brown BD, Gnjatic S, Lujambio A, McClain KL, Picarsic J, Allen CE, Merad M. BRAFV600E-induced senescence drives Langerhans cell histiocytosis pathophysiology. Nat Med. 2021 May;27(5):851-861. doi: 10.1038/s41591-021-01304-x. Epub 2021 May 6.
- Results publication: PubMed 29263218Hogstad B, Berres ML, Chakraborty R, Tang J, Bigenwald C, Serasinghe M, Lim KPH, Lin H, Man TK, Remark R, Baxter S, Kana V, Jordan S, Karoulia Z, Kwan WH, Leboeuf M, Brandt E, Salmon H, McClain K, Poulikakos P, Chipuk J, Mulder WJM, Allen CE, Merad M. RAF/MEK/extracellular signal-related kinase pathway suppresses dendritic cell migration and traps dendritic cells in Langerhans cell histiocytosis lesions. J Exp Med. 2018 Jan 2;215(1):319-336. doi: 10.1084/jem.20161881. Epub 2017 Dec 20.
- Results publication: PubMed 41035796Cao XX, Zhu Q, Cai Z, Ma J, Zhou H, Chang L, Zhong LP, Wu ZL, Wang X, Han P, Lin HM, Wei Z, Guo JY, Zheng Y, Li J. Luvometinib in patients with Langerhans cell histiocytosis, Erdheim-Chester disease, and other histiocytic neoplasms: a single-arm, multicentre, phase 2 study. EClinicalMedicine. 2025 Sep 17;88:103486. doi: 10.1016/j.eclinm.2025.103486. eCollection 2025 Oct.
- Results publication: PubMed 40751881Keam SJ. Luvometinib: First Approval. Drugs. 2025 Sep;85(9):1177-1183. doi: 10.1007/s40265-025-02217-6. Epub 2025 Aug 2.
- Results publication: PubMed 36884302Whitlock JA, Geoerger B, Dunkel IJ, Roughton M, Choi J, Osterloh L, Russo M, Hargrave D. Dabrafenib, alone or in combination with trametinib, in BRAF V600-mutated pediatric Langerhans cell histiocytosis. Blood Adv. 2023 Aug 8;7(15):3806-3815. doi: 10.1182/bloodadvances.2022008414.
- Results publication: PubMed 37731389Cournoyer E, Ferrell J, Sharp S, Ray A, Jordan M, Dandoy C, Grimley M, Roy S, Lorsbach R, Merrow AC, Nelson A, Bartlett A, Picarsic J, Kumar A. Dabrafenib and trametinib in Langerhans cell histiocytosis and other histiocytic disorders. Haematologica. 2024 Apr 1;109(4):1137-1148. doi: 10.3324/haematol.2023.283295.
- Results publication: PubMed 31513482Donadieu J, Larabi IA, Tardieu M, Visser J, Hutter C, Sieni E, Kabbara N, Barkaoui M, Miron J, Chalard F, Milne P, Haroche J, Cohen F, Helias-Rodzewicz Z, Simon N, Jehanne M, Kolenova A, Pagnier A, Aladjidi N, Schneider P, Plat G, Lutun A, Sonntagbauer A, Lehrnbecher T, Ferster A, Efremova V, Ahlmann M, Blanc L, Nicholson J, Lambilliote A, Boudiaf H, Lissat A, Svojgr K, Bernard F, Elitzur S, Golan M, Evseev D, Maschan M, Idbaih A, Slater O, Minkov M, Taly V, Collin M, Alvarez JC, Emile JF, Heritier S. Vemurafenib for Refractory Multisystem Langerhans Cell Histiocytosis in Children: An International Observational Study. J Clin Oncol. 2019 Nov 1;37(31):2857-2865. doi: 10.1200/JCO.19.00456. Epub 2019 Sep 12.
- Results publication: PubMed 15049016Haupt R, Nanduri V, Calevo MG, Bernstrand C, Braier JL, Broadbent V, Rey G, McClain KL, Janka-Schaub G, Egeler RM. Permanent consequences in Langerhans cell histiocytosis patients: a pilot study from the Histiocyte Society-Late Effects Study Group. Pediatr Blood Cancer. 2004 May;42(5):438-44. doi: 10.1002/pbc.20021.
- Results publication: PubMed 38501389Parekh D, Lin H, Batajoo A, Peckham-Gregory E, Karri V, Stanton W, Scull B, Fleishmann R, El-Mallawany N, Eckstein OS, Prudowsky ZD, Gulati N, Agrusa JE, Ahmed AZ, Chu R, Dietz MS, Goldman SC, Hogarty MD, Imran H, Intzes S, Kim JM, Kopp LM, Levy CF, Neff P, Pillai PM, Sisk BA, Schiff DE, Trobaugh-Lotrario AD, Walkovich K, McClain KL, Allen CE. Clofarabine monotherapy in aggressive, relapsed and refractory Langerhans cell histiocytosis. Br J Haematol. 2024 May;204(5):1888-1893. doi: 10.1111/bjh.19376. Epub 2024 Mar 19.
- Individual participant dataSharing planned: No. IPD might be shared in the future upon approval by the ethics committee and under a data use agreement.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Prednisone, Vincristine and Mercaptopurine in people with Langerhans Cell Histiocytosis (LCH), run by West China Second University Hospital at 11 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 24 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Xue Tang (86+18280145819, txily0912@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Event-Free survival rate (time frame: From Day 1 until the date of first event or last follow-up, assessed up to 2 years.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07431060, which also lists 14 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2026.