Langerhans cell histiocytosis
Conditions
Interventions
Test group:Torametinib + vemurafenibv
Sponsors
Shanghai Sixth People's Hospital
Eligibility
Sex/Gender
All
Age
12 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. The patient voluntarily joined this study and signed the informed consent form; 2. Age >=12 years old, gender not limited; 3. Histologically confirmed Langerhans cell histiocytosis (LCH); 4. Relapsed/refractory LCH 5. Patients involving multiple systems (more than one system) or multiple lesions involving a single system (more than one lesion); 6. The previous genetic test results showed positive BRAF mutation. 7. Have failed systemic standard chemotherapy in the past; 8. ECOG score: 0-2 points; 9. According to RECISTv1.1 assessment, there is at least one assessable lesion; 10. Expected survival > 12 weeks; 11. Normal functions of major organs and bone marrow: • Blood routine: Hemoglobin >=90 g/L (no blood transfusion within 14 days); The absolute neutrophil count was >=1.5×10^9/L; Platelet count >=100×10^9/L; • Liver function: Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) =30 g/L; • Renal function: Serum creatinine 60 mL/ minute; • Cardiac function: Echocardiography showed that the left ventricular ejection fraction (LVEF) was >=55%; The QTcF of the electrocardiogram is <=480ms; Creatine kinase (CK) <=1×ULN, troponin/hypersensitive troponin <=1×ULN; • Coagulation function: The International normalized ratio (INR) of prothrombin time <=1.5×ULN; Activated partial thromboplastin time (APTT) <=1.5×ULN; 12. Women of childbearing age must have a negative result of the pregnancy test (serum or urine) within 14 days before enrollment, and voluntarily adopt appropriate contraceptive methods during the observation period and within 3 months after the last administration of the study drug; For men, surgical sterilization should be performed or consent should be given to use appropriate contraceptive methods during the observation period and within 3 months after the last administration of the study drug.
Exclusion criteria
Exclusion criteria: 1. Have previously received BRAF inhibitors or MEK inhibitors; 2. Receive any other anti-cancer treatment (such as chemotherapy, other targeted therapy, other investigational drugs, radiotherapy, traditional Chinese medicine treatment, etc.) other than that in this study within 2 weeks before the first use of the study drug; 3. Impaired cardiac function or clinically significant cardiovascular and cerebrovascular diseases, including but not limited to any of the following: • Acute coronary syndrome occurred within 6 months before the start of treatment, including acute myocardial infarction, unstable angina pectoris, coronary artery bypass grafting, coronary angioplasty and stent implantation; • Symptomatic congestive heart failure (New York Heart Association [NYHA] grade =II); There is evidence of clinically significant arrhythmia and/or conduction abnormalities within 6 months before the start of treatment or at present; • Poorly controlled hypertension (systolic blood pressure >=140 and/or diastolic blood pressure >=90 mmHg under drug control); • Abnormal morphology of heart valves recorded by echocardiography (>= grade 2) Note: Patients with abnormal morphology of grade 1 heart valves (such as mild regurgitation/stenosis) are allowed to be enrolled, but patients with moderate valve thickening are prohibited from being enrolled. • Have a history of congenital long QT syndrome; Or those who take drugs known to prolong the QT interval and cannot guarantee drug withdrawal during the study period; 4. Previous or screened retinal diseases, such as: retinal vein occlusion (RVO), retinal artery occlusion, retinal vasculitis, diabetic retinopathy, hypertensive retinopathy, retinal telangiectasia (cost disease), retinal pigment epithelial detachment (RPED), etc. There are risk factors for RVO during screening (for example, uncontrolled glaucoma or a history of high intraocular pressure, high viscosity or hypercoagulable syndrome); Retinal diseases such as RPED; 5. Interstitial lung disease or interstitial pneumonia, including patients with clinically significant radiation pneumonitis (i.e., those that affect daily living activities or require intervention treatment); 6. Positive for human immunodeficiency virus (HIV) antibody, positive for syphilis antibody (Anti-TP), positive for hepatitis C virus (HCV) antibody and positive for HCV RNA, positive for hepatitis B virus surface antigen (HBsAg) and positive for HBV DNA (HBsAg positive requires further testing for HBV DNA) HBV DNA>=200 IU/ml, or >=10^3 copy number /ml; 7. History of allogeneic bone marrow transplantation or organ transplantation; 8. Within 2 weeks before the first administration, there is an uncontrollable active infectious disease (such as: requiring intravenous infusion of antibiotics, antifungal or antiviral drugs), or an unexplained fever >38.5°C occurs during the screening period/before the first administration; 9. Uncorrectable electrolyte abnormalities (hypokalemia, hypomagnesemia, and hypocalcemia detected by blood biochemical tests); 10. There have been or are currently neuromuscular diseases related to elevated CK (such as inflammatory myopathy, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy, rhabdomyolysis syndrome); 11. Arterial/venous thrombosis events that occurred within 6 months before the first medication, such as cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thro
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective response rate;Determine the recommended dose for adolescent subjects in Phase II;Pharmacokinetic characteristics; | — |
Secondary
| Measure | Time frame |
|---|---|
| Duration of relief;Disease control rate;Progression-free survival; | — |
Countries
China
Contacts
Public ContactHaiyan Hu
Shanghai Sixth People's Hospital
Outcome results
None listed