{"entity":{"id":"lch-iii","kind":"trial","name":"LCH-III","aka":[],"tldr":"The Histiocyte Society's third international trial showed that treating multisystem Langerhans cell histiocytosis for a full year, rather than six months, roughly halves the chance of the disease coming back, while adding methotrexate added nothing but toxicity.","summary":"International randomised trial (Gadner et al., Blood 2013), more than 400 patients randomised. In risk-organ-positive disease, adding methotrexate to vinblastine and prednisone did not change response, survival or reactivation; but 12 months of therapy gave 5-year survival of 84% against 62% and 69% in the identically stratified predecessor trials LCH-I and LCH-II, and reduced 5-year reactivation to 27% from 55% and 44%. In risk-organ-negative disease, 12 months of vinblastine-prednisone lowered 5-year reactivation to 37% versus 54% with 6 months (P = 0.03). One year of vinblastine-prednisone became the international standard and the backbone of LCH-IV, which tests further prolongation and the addition of 6-mercaptopurine. The trial predates the discovery that most LCH carries BRAF V600E or other MAPK mutations, which now drive targeted therapy for refractory disease.","status":"positive","asOf":"2026-09-10","links":[{"label":"ClinicalTrials.gov NCT00276757","url":"https://clinicaltrials.gov/study/NCT00276757"},{"label":"Gadner et al., Blood 2013","url":"https://doi.org/10.1182/blood-2012-09-455774"},{"label":"Histiocyte Society: LCH-IV","url":"https://histiocytesociety.org/LCH-IV"}],"tags":["nci-coverage","paediatric","histiocytosis"],"related":[],"cancers":["langerhans-cell-histiocytosis","lch-multisystem","lch-single-system"],"sections":[],"technologies":["cytotoxic-chemotherapy"],"targets":["braf"],"drugs":["vinblastine","methotrexate"],"companies":[],"institutions":["histiocyte-society"],"pathways":["ras-mapk"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT00276757","phase":"3","setting":"Multisystem Langerhans cell histiocytosis in children: risk-organ-positive patients randomised to vinblastine-prednisone with or without methotrexate (12 months total); risk-organ-negative responders randomised to 6 vs 12 months of vinblastine-prednisone","sponsor":"Histiocyte Society","result":"12 vs 6 months of vinblastine-prednisone: 5-year reactivation 37% vs 54% in risk-organ-negative disease; methotrexate added no benefit.","started":"2001-04","yearReported":2013,"enrolled":376,"enrolledBasis":"registry","outcomes":[{"endpoint":"5-year reactivation rate, risk-organ-negative","primary":true,"unit":"%","arms":[{"name":"12 months vinblastine-prednisone","value":37},{"name":"6 months vinblastine-prednisone","value":54}],"p":"0.03","source":"https://doi.org/10.1182/blood-2012-09-455774"},{"endpoint":"5-year reactivation rate, risk-organ-positive (both arms, 12 months)","unit":"%","arms":[{"name":"LCH-III","value":27},{"name":"LCH-I (historical, 6 months)","value":55},{"name":"LCH-II (historical, 6 months)","value":44}],"source":"https://doi.org/10.1182/blood-2012-09-455774"}],"replication":"Historical comparison with LCH-I and LCH-II for the risk-organ-positive stratum; LCH-IV (NCT02205762) is testing 12 vs 24 months."},"route":"/trials/lch-iii/","neighbours":{"cancer":[{"id":"langerhans-cell-histiocytosis","kind":"cancer","name":"Langerhans cell histiocytosis (LCH)","route":"/cancers/langerhans-cell-histiocytosis/"},{"id":"lch-multisystem","kind":"cancer","name":"Multisystem Langerhans cell histiocytosis (with or without risk-organ involvement)","route":"/cancers/lch-multisystem/"},{"id":"lch-single-system","kind":"cancer","name":"Single-system Langerhans cell histiocytosis (bone, skin or one other organ)","route":"/cancers/lch-single-system/"}],"technology":[{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"}],"target":[{"id":"braf","kind":"target","name":"BRAF","route":"/targets/braf/"}],"drug":[{"id":"methotrexate","kind":"drug","name":"Methotrexate","route":"/drugs/methotrexate/"},{"id":"vinblastine","kind":"drug","name":"Vinblastine","route":"/drugs/vinblastine/"}],"institution":[{"id":"histiocyte-society","kind":"institution","name":"Histiocyte Society","route":"/institutions/histiocyte-society/"}],"pathway":[{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"}],"paper":[{"id":"paper-lch-iii-therapy-prolongation-multisystem-lch-blood-2013","kind":"paper","name":"LCH-III: therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis","route":"/key-papers/paper-lch-iii-therapy-prolongation-multisystem-lch-blood-2013/"}]}}