To test the safety, efficacy and tolerability of a drug called trametinib and determine the duration of treatment in children with histiocytic cell hyperplasia refractory to conventional therapy.

You may be able to join if

• Lack of mutations in the BRAF gene in tumor tissues and/or ctDNA at any stage of treatment or follow-up, or failure of Vemurafenib treatment in BRAF positive patients.
• Failure of the treatment (at least one of below needs to apply in order for this requirement to be satisfied): a. 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 secondline treatment or b. 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 c. Third or subsequent reactivation of disease with or without risk organ involvement, or d. Progression during Vemurafenib therapy, or e. Reactivation of disease after Vemurafenib therapy has been completed, or f. The appearance of signs of neurodegenerative disorder (ND) in MRI of the CNS.
• Signing of informed consent for trial participation (including for Trametinib treatment) according with current legal regulations.
• Consent to the use of effective contraception throughout the Trametinib administration period and a minimum of 1 year after discontinuation in patients at puberty and sexual maturity.
• Participation in HISTIOGEN trial.