Optimization of the Time and Dosage of Vemurafenib in BRAF Positive Juvenile Patients With Refractory Histiocytosis

Inclusion Criteria: 1. The presence of mutations in the BRAF gene in tumor tissues and/or in circulating tumor DNA (ctDNA) at any stage of treatment or follow-up. 2. Failure of the treatment (at least one of below needs to apply in order for this requirement to be satisfied): 1. Progression on the I and/or II line treatment, including at least one risk organ; prior treatment should include a minimum of 6 weeks of weekly Vinblastine with a minimum of 28 days prednisolone or minimum 2 cycles of Cytosine Arabinoside in 4-day cycles and/or Cladribine in 5-day cycles as a 2nd line treatment, minimum 2 cycles, or other second-line treatment or 2. Disease reactivation after an initial response to treatment with Vimblastine and prednisolone as the first line and/or no response to second line treatment using one of two drugs: Cytosine Arabinoside in 4-day cycles and/or Cladribine in 5-day cycles, minimum 2 cycles, or other I/ II line treatment or occurrence of involvement of at least one risk organ or 3. Third or subsequent reactivation of disease with or without risk organ involvement, or 4. Reactivation of disease after Vemurafenib therapy has been completed, or 5. The appearance of signs of neurodegenerative disorder (ND) in MRI of the central nervous system (CNS). 3. Signing of informed consent for trial participation (including for Vemurafenib treatment) according with current legal regulations. 4. Consent to the use of effective contraception throughout the Vemurafenib administration period and a minimum of 1 year after discontinuation in patients at puberty and sexual maturity. 5. Participation in HISTIOGEN trial. Exclusion Criteria: 1. Lack of inclusion criteria. 2. Pregnancy and breastfeeding . 3. Hypersensitivity to the study drug or any of its ingredients. 4. Iritis, uveitis, obstruction of the retinal veins. 5. Simultaneous treatment with other drugs which might interact with Vemurafenib. 6. Persistent toxicity related to prior therapy, making it impossible to treat with Vemurafenib. 7. Diagnosis of other malignancies before study inclusion. 8. Other acute or persistent disorders, behaviors or abnormal laboratory test results, which might increase the risk related to the participation in this clinical trial or to taking the study drug, or which might influence the interpretation of the study results, or which, in the investigator's opinion, disqualify a patient from participating in the trial.