[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"langerhans-cell-histiocytosis-lch\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:langerhans-cell-histiocytosis-lch":35},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,5,0,[8,78,107,126,152],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":15,"eligibilityCriteria":16,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":26,"conditions":27,"keywords":47,"overallStatus":65,"whyStopped":4,"lastUpdateSubmitDate":66,"lastUpdatePostDateStruct":67,"startDateStruct":70,"completionDateStruct":72,"leadSponsor":74,"locationsCount":77},"100626796","phase-2-determine-trial-treatment-arm-07-dabrafenib-in-combination-with-trametinib-in-adult-paediatric-and-teenageyoung-adult-patients-with-braf-v600-mutation-positive-cancers-100626796",false,"NCT07440290","DETERMINE Trial Treatment Arm 07: Dabrafenib in Combination With Trametinib in Adult, Paediatric and Teenage\u002FYoung Adult Patients With BRAF V600 Mutation-Positive Cancers.","DETERMINE (Determining Extended Therapeutic Indications for Existing Drugs in Rare Molecularly Defined Indications Using a National Evaluation Platform Trial): An Umbrella-Basket Platform Trial to Evaluate the Efficacy of Targeted Therapies in Rare Adult, Paediatric and Teenage\u002FYoung Adult (TYA) Cancers With Actionable Genomic Alterations, Including Common Cancers With Rare Actionable Alterations. Treatment Arm 07: Dabrafenib in Combination With Trametinib in Adult, Paediatric and TYA Patients With BRAF V600 Mutation-Positive Cancers.","DETERMINE","THE PATIENT MUST FULFIL THE ELIGIBILITY CRITERIA WITHIN THE DETERMINE MASTER PROTOCOL (NCT05722886) AND WITHIN THE TREATMENT ARM 07 (DABRAFENIB AND TRAMETINIB) OUTLINED BELOW\\* \\*When dabrafenib- and trametinib-specific inclusion\u002Fexclusion criteria or precautions below differ from those specified in the Master Protocol, the dabrafenib- and trametinib-specific criteria will take precedence.\n\nInclusion criteria:\n\nA. Confirmed diagnosis of a malignancy harbouring an oncogenic alteration in BRAF V600, including Langerhans cell histiocytosis, using an analytically validated next-generation sequencing method.\n\nB. Patients ≥1 year old and ≥8 kg in body weight.\n\nC. Women of childbearing potential are eligible provided that they meet the following criteria:\n\n• Have a negative serum or urine pregnancy test before enrolment and;\n\n• Agree to use one form of a non-hormonal highly effective contraception method (a method that can achieve a failure rate of \\\u003C1% when used consistently and correctly; the requirement for non-hormonal method is because dabrafenib may decrease the efficacy of oral or any systemic hormonal contraceptives), such as: i. intrauterine device (IUD), ii. bilateral tubal occlusion, bilateral tubal ligation (at least six weeks before taking trial treatment), iii. vasectomised partner, iv. total sexual abstinence. Effective from the first administration of dabrafenib and trametinib (whichever is first), throughout the trial and for two weeks following discontinuation of dabrafenib and for 16 weeks following discontinuation of trametinib (whichever is later).\n\nPatients who are breastfeeding must be willing to discontinue breastfeeding from the start of treatment, throughout the trial and for two weeks following discontinuation of dabrafenib and for 16 weeks following discontinuation of trametinib (whichever is later).\n\nD. Male patients with partners who are women of childbearing potential are eligible provided that they agree to the following, from the first administration of dabrafenib and trametinib (whichever is first), throughout the trial and for two weeks after the last administration of dabrafenib and 16 weeks after the last administration of trametinib (whichever is later):\n\n* Agree to take measures not to father children by using a barrier method of contraception (male condom plus spermicide) or to sexual abstinence.\n* Non-vasectomised male partners with partners who are women of childbearing potential should also be advised of the benefit for their partner of using a highly effective method of contraception, such as:\n\n  i. combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation \\[oral, intravaginal or transdermal\\]), ii. progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable), iii. IUD, iv. intrauterine hormone-releasing system (IUS), v. bilateral tubal occlusion, vi. total sexual abstinence.\n* Male patients with pregnant or breastfeeding partners must be advised to use barrier method contraception (male condom) to prevent drug exposure of the foetus or neonate, even if vasectomised.\n* Male patients must refrain from donating sperm for the same period.\n\nE. Patients must be able and willing to undergo a fresh tissue biopsy at baseline and blood samples for translational research. Note that for patients with haematological malignancies or neuroblastomas, blood, bone marrow aspiration and\u002For trephine or lymph node biopsy samples may be taken.\n\nF. Adequate organ function as per haematological and biochemical indices within the ranges defined in the protocol. These measurements should be performed to confirm the patient's eligibility\n\nExclusion criteria:\n\nA. Diagnosis of one of the following BRAF V600E mutation-positive cancers:\n\n* Colorectal cancer in adult (≥18 years) patients;\n* Unresectable or metastatic melanoma in adult (≥18 years) patients;\n* Advanced non-small cell lung cancer in adult (≥18 years) patients;\n* Gliomas harbouring a BRAF V600E mutation in paediatric (1 to \\\u003C16 years) or TYA (16 to \\\u003C18 years) patients.\n\nB. Previous treatment with dabrafenib and trametinib in combination (or other BRAF and MEK inhibitors in combination) for the current indication.\n\nC. Female patients who are pregnant, breastfeeding or planning to become pregnant during the trial or for two weeks following their last dose of dabrafenib or 16 weeks following their last dose of trametinib, whichever is later.\n\nD. Known hypersensitivity to dabrafenib or trametinib or any of the excipients. See the current relevant SmPCs (UK) for the full lists.\n\nE. Patients with a history of retinal vein occlusion.\n\nF. Any impairment of gastrointestinal (GI) function of uncontrolled GI disease that may significantly alter the administration or absorption of dabrafenib and\u002For trametinib (e.g. history of diverticulitis, metastases to the GI tract, uncontrolled Crohn's disease, uncontrolled ulcerative diseases, uncontrolled nausea, vomiting, diarrhoea, malabsorption syndrome or short gut syndrome).\n\nG. Clinically significant cardiac or cerebrovascular disease as defined by:\n\n* Unstable angina within three months prior to screening;\n* Myocardial infarction within three months prior to screening;\n* History of documented congestive heart failure (New York Heart Association functional classification III\u002FIV) etc.\n\nPatients with a cerebrovascular event (including stroke or transient ischaemic attack \\[TIA\\]) within three months prior to screening.\n\n• Patients with primary central nervous system (CNS) tumours may be considered unless intratumoural bleeding has occurred within two weeks prior to the first dose of dabrafenib and trametinib, and patients with punctate CNS haemorrhages \\\u003C3 mm may be considered.\n\nH. Patients who were administered a live, attenuated vaccine within 28 days prior to initiation of treatment, or anticipation of need for such a vaccine during investigational medicinal product (IMP) treatment or within six months after the final dose of dabrafenib and trametinib.\n\nI. Known active infections (bacterial, fungal or viral) that would interfere with the assessment of safety or efficacy of dabrafenib and trametinib including human immunodeficiency virus (HIV) positivity. Patients with history of testing positive for HIV infection are eligible provided that each of the following conditions are met:\n\n* CD4 count ≥350\u002FµL;\n* Undetectable viral load;\n* Receiving antiretroviral therapy (ART) that does not interact with IMP (patients should be on established ART for at least four weeks); and\n* No HIV\u002Facquired immune deficiency syndrome associated opportunistic infection in the last 12 months.\n\nJ. Any clinically significant concomitant disease or condition (or its treatment) that could interfere with the conduct of the trial (including absorption of oral medications) that would, in the opinion of the Investigator, pose an unacceptable risk to the patient in this trial.","ALL","1 Year",{"count":20,"type":21},30,"ESTIMATED","INTERVENTIONAL",[24,25],"PHASE2","PHASE3","This clinical trial is looking at two drugs called dabrafenib and trametinib. Dabrafenib and trametinib are approved as standard of care treatment for adult patients with melanoma (a type of skin cancer) or lung cancer and in children with glioma (a type of brain tumour). This means they have gone through clinical trials and been approved by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK. Dabrafenib and trametinib work in patients with a particular mutation in their cancer known as BRAF V600.\n\nInvestigators now wish to find out if they will be useful in treating patients with other cancer types which have the same mutation. If the results are positive, the study team will work with the NHS and the Cancer Drugs Fund to see if these drugs can be routinely accessed for patients in the future.\n\nThis trial is part of a trial programme called DETERMINE. The programme will also look at other anti-cancer drugs in the same way, through matching the drug to rare cancer types or ones with specific mutations.",[28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46],"Haematological Malignancy","Malignant Neoplasm","Lymphoproliferative Disorders","Neoplasms by Histologic Type","Neoplasms by Site","Gastrointestinal Cancer","Non-Melanoma Skin Cancer (NMSC)","Langerhans Cell Histiocytosis (LCH)","Cancer","Erdheim-Chester Disease","Thyroid Carcinoma, Papillary","Ovarian Neoplasms","Colorectal Neoplasms","Laryngeal Neoplasms","Carcinoma, Non-Small Cell-Lung","Glioma","Multiple Myeloma","Thyroid Carcinoma, Anaplastic","Solid Tumour",[48,49,36,50,51,52,53,54,55,56,32,57,58,59,60,61,62,63,64],"Adult","Antineoplastic Agents","Child","Dabrafenib","Malignancy","Malignant Neoplasms","Molecular Targeted Therapy","Mutation","Neoplasms by Histologic Site","Paediatric","Precision Medicine","Proto-Oncogene Proteins B-raf","Protein Kinase Inhibitors","Rare","Trametinib","Tumour-Agnostic","Young adult","NOT_YET_RECRUITING","2026-02-23",{"date":68,"type":69},"2026-02-27","ACTUAL",{"date":71,"type":21},"2026-02",{"date":73,"type":21},"2029-10",{"name":75,"class":76},"Cancer Research UK","OTHER",27,{"id":79,"slug":80,"hasResults":11,"nctId":81,"briefTitle":82,"officialTitle":83,"acronym":4,"eligibilityCriteria":84,"healthyVolunteers":11,"sex":17,"minAge":85,"maxAge":86,"enrollmentInfo":87,"targetDuration":4,"studyType":22,"phases":89,"briefSummary":91,"conditions":92,"keywords":93,"overallStatus":96,"whyStopped":4,"lastUpdateSubmitDate":97,"lastUpdatePostDateStruct":98,"startDateStruct":100,"completionDateStruct":102,"leadSponsor":104,"locationsCount":106},"100626086","modified-lch-iii-regimen-with-or-without-luvometinib-for-multisystem-pediatric-langerhans-cell-histiocytosis-100626086","NCT07431060","Modified LCH-III Regimen With or Without Luvometinib for Multisystem Pediatric Langerhans Cell Histiocytosis","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","Inclusion Criteria:\n\n1. Children aged 0-18 years, of either sex.\n2. Pathologically confirmed diagnosis of Langerhans cell histiocytosis (LCH) with positive staining for CD1a and\u002For CD207 (Langerin), and no prior treatment specifically directed against LCH.\n3. Multisystem involvement of LCH, as determined by clinical and imaging evaluation.\n4. Provision of written informed consent (by parent\u002Flegal guardian and, where appropriate, assent from the child), with willingness to comply with the study treatment regimen and follow-up assessments.\n\nExclusion Criteria:\n\n1. 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.\n2. History of a second (secondary) malignancy.\n3. QTcF interval \\> 0.47 seconds on electrocardiogram performed prior to enrollment.\n4. 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.\n5. 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.\n6. Refusal or inability to provide written informed consent (or assent, as applicable).","0 Years","18 Years",{"count":88,"type":21},120,[90],"NA","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.\n\nMild (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.\n\nMore 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\u002Frefractory 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.\n\nNo MAPK inhibitors were previously approved specifically for LCH. In 2025, luvometinib (developed by Fosun Pharma, China; a selective MEK1\u002F2 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.\n\nLaboratory 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.\n\nSmall 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.\n\nThis 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.",[35],[94,95],"Langerhans Cell Histiocytosis","Luvometinib","RECRUITING","2026-02-20",{"date":99,"type":69},"2026-02-24",{"date":101,"type":21},"2026-02-13",{"date":103,"type":21},"2030-12-31",{"name":105,"class":76},"West China Second University Hospital",11,{"id":108,"slug":109,"hasResults":11,"nctId":110,"briefTitle":111,"officialTitle":112,"acronym":4,"eligibilityCriteria":113,"healthyVolunteers":11,"sex":17,"minAge":85,"maxAge":86,"enrollmentInfo":114,"targetDuration":4,"studyType":22,"phases":116,"briefSummary":117,"conditions":118,"keywords":4,"overallStatus":96,"whyStopped":4,"lastUpdateSubmitDate":119,"lastUpdatePostDateStruct":120,"startDateStruct":122,"completionDateStruct":124,"leadSponsor":125,"locationsCount":106},"100621481","luvometinib-in-pediatric-ss-lch-with-special-site-singlemultifocal-bone-lesions-100621481","NCT07371182","Luvometinib in Pediatric SS-LCH With Special-site Single\u002FMultifocal Bone Lesions","A Multi-center, Open-label, Single-arm Study of Luvometinib Monotherapy in Pediatric Langerhans Cell Histiocytosis With Single-system Special-site Single and Multifocal Bone Involvement","Inclusion Criteria:\n\n1. Children aged 0-18 years, both sexes.\n2. Pathologically confirmed diagnosis of LCH (CD1a+ and\u002For CD207+), with no prior treatment specific to LCH.\n3. Patients assessed as having single-system multifocal bone involvement, single-site bone involvement at central nervous system risk sites (central nervous system risk sites include craniofacial region \\[excluding parietal, occipital, and frontal bones\\], orbital, ear, and oral regions), or single-site vertebral bone involvement with intraspinal space-occupying lesion compressing the spinal cord.\n4. Signed informed consent, willing to receive treatment according to this protocol and undergo follow-up.\n\nExclusion Criteria:\n\n1. Patients with other underlying diseases, such as primary immunodeficiency, heart failure, renal insufficiency, hepatitis virus infection, HIV infection, post-organ transplantation, etc.\n2. Secondary malignancy.\n3. QTcF \\> 0.47 seconds on electrocardiogram prior to enrollment.\n4. Ophthalmologic screening prior to enrollment reveals retinal vein occlusion, retinal pigment epithelial detachment, or other ocular diseases.\n5. Patients with LCH carrying category 3 MEK mutations, specifically the following mutation sites: L98\\_I103del, L98\\_K104del, P105\\_A106del, P105\\_I107delinsL, L101\\_I103delinsF, E102\\_I103delinsF, E102\\_I103del, E102\\_I103delinsV, E102\\_I103delinsVN, E102\\_K104delinsQ, I103\\_A106del.\n6. Refusal to sign the informed consent form.",{"count":115,"type":21},62,[90],"Langerhans cell histiocytosis (LCH) is the most common type of histiocytic disorder in children, affecting about 2.6 to 8.9 out of every million kids each year. It can look very different from one child to another-some cases get better on their own-but when it affects special bones (like the base of the skull, temporal bone, eye socket, or spine) or when there are multiple bone lesions in one system, children often face a higher risk of long-term complications and the disease coming back.Current guidelines in China and around the world recommend treating these children with whole-body therapy, usually a chemotherapy combination of vinblastine and prednisone. However, even with longer treatment courses, about 27.6% of children with multiple bone lesions still have the disease return, and less than 70% stay free of events after 5 years. Some even develop lasting nerve system problems.\n\nIn recent years, researchers discovered that nearly all children with LCH have overactive MAPK signaling pathways in their cells. This discovery opened the door to using MAPK inhibitors as a new treatment. Studies have shown that these drugs work well and are safe for children with relapsed or hard-to-treat LCH. Even better, in some kids with single-system bone disease, the disease did not come back after stopping the drug-suggesting it might even cure certain cases.\n\nLuvometinib (also called FCN-159), a new MAPK inhibitor developed by Fosun Pharma in Shanghai, was approved in 2025 for treating adult LCH. A Phase II clinical study showed very encouraging results: 82.8% of patients saw their disease improve or disappear, and 74.4% stayed free of progression after 12 months. The drug was well tolerated, with side effects that were mild and manageable-no serious problems forced anyone to stop treatment.Compared to traditional chemotherapy, luvometinib has fewer and milder side effects, does not weaken the immune system, and lets children continue normal daily life and school. It is a simple oral pill taken once a day, so there's no need for intravenous lines or hospital stays, making treatment much easier and improving quality of life for both the child and the family.",[35],"2026-01-18",{"date":121,"type":69},"2026-01-27",{"date":123,"type":21},"2026-06-19",{"date":103,"type":21},{"name":105,"class":76},{"id":127,"slug":128,"hasResults":11,"nctId":129,"briefTitle":130,"officialTitle":131,"acronym":4,"eligibilityCriteria":132,"healthyVolunteers":11,"sex":17,"minAge":133,"maxAge":4,"enrollmentInfo":134,"targetDuration":4,"studyType":22,"phases":136,"briefSummary":137,"conditions":138,"keywords":4,"overallStatus":96,"whyStopped":4,"lastUpdateSubmitDate":142,"lastUpdatePostDateStruct":143,"startDateStruct":145,"completionDateStruct":147,"leadSponsor":149,"locationsCount":151},"100527854","phase-2-mirdametinib-in-histiocytic-disorders-100527854","NCT06153173","Mirdametinib in Histiocytic Disorders","A Phase II Trial of the MEK Inhibitor Mirdametinib in Histiocytic Disorders","Inclusion Criteria:\n\n1. Subjects must be ≥ 2 years of age AND have a diagnosis of a histiocytic disorder that requires systemic therapy\n\n   * If patient has had a diagnostic biopsy, biopsy must be reviewed and confirmed by CCHMC pathologist as feasible\n   * If patient has had a biopsy but has not had molecular testing done, must have tissue available for mutational analysis\n   * If patient has isolated pituitary\u002FCNS disease or situations where biopsy is not feasible, positive ddPCR blood test for mutation associated with histiocytic neoplasm with clinical features of histiocytosis is sufficient\n2. Must have measurable disease on PET scan or brain MRI\n3. Subjects must demonstrate adequate organ function as defined:\n\n   * Renal: maximum serum creatinine 2x the upper limit of normal (ULN) OR a creatinine clearance or radioisotope GFR ≥ 70ml\u002Fmin\u002F1.73 m2\n   * Liver: ALT ≤ 3x ULN AND normal INR (≤ 1.5)\n   * Hematologic: Hematology: Albumin ≥ 2.8 g\u002FdL; Absolute neutrophil count ≥ 1.5 x 109\u002FL; Platelets ≥ 100 x 109\u002FL; Hemoglobin ≥ 9.0 g\u002FdL\n   * Patients with organ function abnormalities outside of these thresholds deemed to be the result of histiocytic disease will be considered eligible\n\nExclusion Criteria:\n\n1. Prior therapy with stipulations as described:\n\n   * Myelosuppressive Chemotherapy: Must not have received any cytotoxic chemotherapy which impacts the growth and development of cells in the bone marrow within 14 days of enrollment onto this study (i.e. cytarabine, cladribine, clofarabine, mercaptopurine, methotrexate, vinblastine)\n   * MEK Inhibitors: Must not have received a MEK inhibitor within 30 days (or 5 half-lives, whichever is longer) of enrollment, NOR have had disease progression on MEK inhibitor\n   * Steroids: Due to the increased risk of an ocular event, the use of systemic oral, inhaled, or ocular glucocorticoid therapy is prohibited within 14 days prior to first dose of mirdametinib. Throughout the treatment period, short term glucocorticoid treatment (30 days or less) is permitted. Any patients requiring long-term steroid use (more than 30 consecutive days) are not eligible. The exception to this rule is subjects with endocrine deficiencies who require physiologic steroids\n   * Radiation: Must not have received radiation within 14 days of study enrollment or have received radiation to the orbit at any time\n2. Risk factors for retinal vein occlusion (RVO) are listed. Exclusion should be considered by clinical discretion if they have any of the following risk factors for RVO at screening:\n\n   * Intraocular pressure (IOP) \\> 21 mmHg; if IOP is unable to be obtained (eg age, cooperation, tolerability), ophthalmologist's exam findings and overall assessment will be utilized. If in the ophthalmologist's assessment there are no signs of raised IOP, the subject will be considered eligible for this parameter\n   * Glaucoma or any significant abnormality (≥ grade 2) on ophthalmologic exam that is uncontrolled with intervention\n   * Serum cholesterol \\> 300 mg\u002FdL\n   * Serum triglycerides \\> 300 mg\u002FdL\n   * Hyperglycemia (either fasting blood glucose \\> 125 mg\u002FdL OR random blood glucose \\> 200 mg\u002FdL)\n   * Uncontrolled hypertension (participants ≤ 12 years of age with a blood pressure ≥ 95th percentile for age + 12 mmHg; participants ≥ 13 years of age with a blood pressure ≥ 140\u002F90 mm Hg) unresolved on repeat measurement\n3. LVEF \\\u003C 55% at screening OR history of clinically significant cardiac disease, unless deemed to be the direct result of disease\n4. Subjects who are pregnant or breastfeeding, or are at risk of pregnancy or fathering a baby and are unable to use acceptable methods of birth control during the length of the study","2 Years",{"count":135,"type":21},40,[24],"The purpose of this study is to see if treatment with mirdametinib in patients with Langerhans cell histiocytosis (LCH) or other histiocytic disorders will be better than current treatments and with fewer side effects.",[35,139,140,141],"Juvenile Xanthogranuloma (JXG)","Rosai-Dorfman Disease (RDD)","Histiocytic Disorders","2025-09-10",{"date":144,"type":69},"2025-09-16",{"date":146,"type":69},"2024-02-05",{"date":148,"type":21},"2031-03",{"name":150,"class":76},"Children's Hospital Medical Center, Cincinnati",1,{"id":153,"slug":154,"hasResults":11,"nctId":155,"briefTitle":156,"officialTitle":157,"acronym":4,"eligibilityCriteria":158,"healthyVolunteers":11,"sex":17,"minAge":85,"maxAge":86,"enrollmentInfo":159,"targetDuration":4,"studyType":22,"phases":161,"briefSummary":162,"conditions":163,"keywords":4,"overallStatus":96,"whyStopped":4,"lastUpdateSubmitDate":164,"lastUpdatePostDateStruct":165,"startDateStruct":167,"completionDateStruct":169,"leadSponsor":171,"locationsCount":151},"100594698","phase-2-real-world-study-of-darafenib-or-trametinib-and-clofarabine-for-high-riskrecurrentrefractory-langerhans-cell-histiocytosis-in-children-100594698","NCT07022834","Real-world Study of Darafenib or Trametinib and Clofarabine for High-risk\u002FRecurrent\u002FRefractory Langerhans Cell Histiocytosis in Children","A Real-world Investigation of the Combination of Darafenib or Trametinib and Clofarabine in the Treatment of High-risk, Recurrent, or Refractory Pediatric Patients With Langerhans Cell Histiocytosis.","Inclusion Criteria:\n\n1. Children aged 0-18 with LCH (CD1a+\u002FCD207+);\n2. Initial LCH diagnosis with hematopoietic, liver, or spleen involvement;\n3. LCH patients with disease progression or reactivation after chemotherapy (e.g., prednisone, vincristine, cytarabine, clarithromycin) or targeted therapy;\n4. Consent to treatment and follow-up;\n5. ECOG score ≥ 2, Lansky score ≥ 50, organ function suitable for chemotherapy.\n\nExclusion Criteria:\n\n1. Other underlying diseases (e.g., primary immunodeficiency, heart\u002Fkidney failure, hepatitis, HIV, organ transplant);\n2. Secondary tumor;\n3. Recent chemotherapy, radiotherapy, or MAPK inhibitor use with lingering adverse effects;\n4. Ongoing nephrotoxic drug use;\n5. Refusal to consent.\n\nExit Criteria:\n\n1. Allergies to dabrafenib or trametinib and clofarabine；\n2. Disease progression after 3 months on dabrafenib or trametinib；\n3. Severe toxic side effects from clofarabine (grade 4 non-infectious non-hematological toxicity, SIRS, capillary leak syndrome)； 4）The doctor recommends halting the current treatment plan for the patient's benefit.",{"count":160,"type":21},20,[24],"Langerhans cell histiocytosis (LCH) is the most common histiocytosis in children, with an incidence of 2.6-8.9 per million. It is an inflammatory myeloid tumor with varied symptoms. Mild cases often resolve spontaneously, while severe cases can affect multiple organs and be life-threatening. LCH affecting the liver, spleen, or hematopoietic system has a poor prognosis and is high-risk group. The LCH-III study showed that low-risk children respond well to prednisone and vinblastine, with nearly 100% survival, but high-risk children's survival is about 80%, with a 30% reactivation rate.Long-term studies reveal that about 50% of patients are resistant to prednisone and vinblastine, leading to progression and recurrence.\n\nExcept combination of prednisone and vinblastine, cladribine (introduced in 1998) and MAPK inhibitors (introduced in 2014), have lowered the mortality rate of LCH in children. Cladribine, a nucleoside analogue, is used for treating recurrent acute myeloid leukemia in children by disrupting DNA synthesis. In the LCH-98-S regimen, low-risk children with LCH responded well to moderate doses of cladribine, but 44% of high-risk children still faced disease progression. Later studies showed that high-dose cladribine with medium-dose cytarabine increased survival in refractory LCH from 30% to 85%, but also raised chemotherapy toxicity, with some cases experiencing severe hematological toxicity and half of the deaths resulting from chemotherapy complications. Clofarabine, a nucleoside analogue, inhibits ribonucleotide reductase and DNA polymerase, offering stronger anti-tumor effects and fewer side effects than cladribine and fludarabine in treating refractory leukemia. Case reports show that LCH patients unresponsive to cladribine improve with clofarabine treatment at moderate doses (25mg\u002Fm2\u002Fday). A retrospective study of 58 LCH patients using clofarabine (25mg\u002Fm2\u002Fday) showed an 87% progression-free survival rate after one year. While the main side effect was grade 3 or higher hematological toxicity, 98.3% of patients tolerated it and completed treatment. Further prospective studies are needed to determine the optimal dose, duration, long-term efficacy, and complications of clofarabine in children with LCH.\n\nResearch indicates that childhood LCH is often linked to mutations in MAPK pathway genes, with over half of cases involving BRAFV600E mutations. MAPK inhibitors, like vemurafenib, dabrafenib and trametinib, are effective for relapsed and refractory LCH, but they don't eliminate malignant clones, leading to disease reactivation after stopping treatment. Some BRAF-deficient mutation LCH patients resist vemurafenib and dabrafenib, but trametinib can manage the disease in these cases. Activation of the MAPK pathway increases BCL2L1 expression in LCH cells, and rapamycin fails to induce apoptosis in BRAFV600E+ LCH cells, enhancing resistance to cell death. MAPK inhibitors combined with chemotherapy are theoretically more effective at inducing apoptosis in LCH cells and resetting the immune environment to eliminate malignant clones. Two clinical studies confirm their safety and efficacy in treating refractory recurrent LCH. In a follow-up of 10 LCH cases treated with nucleotide analogues and MAPK inhibitors, only 2 patients relapsed after a short treatment duration. Additionally, 19 children with BRAFV600E mutation LCH were treated with cladribine, cytarabine, and vemurafenib, achieving a 100% response rate. Nearly 80% completed treatment without recurrence, and no increase in side effects was observed.\n\nSince 2020, our center treated nearly 40 LCH patients with MAPK inhibitors, including 14 combined with LCH-III chemotherapy. Follow-ups show no severe toxic side effects, aligning with literature. However, most high-risk patients, especially those who stopped oral MAPK inhibitors, had disease reactivation. Two high-risk patients with liver involvement achieved complete liver lesion regression with cladribine. This clinical study aims to assess the efficacy and safety of dabrafenib or trametinib and clofarabine for high-risk\u002Frecurrent\u002Frefractory LCH in children.",[35],"2025-06-07",{"date":166,"type":69},"2025-06-15",{"date":168,"type":69},"2025-06-01",{"date":170,"type":21},"2030-06-01",{"name":105,"class":76}]