A Study to Test the Ability of and Safety of GSK2110183 in Treating Langerhans Cell Histiocytosis

Inclusion Criteria

• •1. Written informed consent is provided. Adolescents will provide assent, with consent provided by parent or legal guardian.
• •2. Prior therapy restrictions:
• •* Refractory/reactivation stratum: Age \>= 12 years of age at the time of study enrollment and Tanner Stage \>2. Subjects less than 18 years old must weigh at least 40 kg.
• •* Treatment-naïve stratum (defined as either no prior treatment or intolerant of first-line treatment with cessation prior to first response evaluation): Age \>= 18 years old
• •3. Histologically- or cytologically-confirmed diagnosis of Langerhans Cell Histiocytosis requiring systemic treatment:
• •* SS-LCH with 'CNS-risk' or 'special site' lesions or 'risk organs' (Includes LCH brain lesions or pituitary infiltration provided that disease is evaluable for treatment response. Patients with isolated pulmonary disease should have recent onset (within 3 years) or demonstrate evidence of active disease on PET or other functional imaging. If isolated pulmonary disease without radiographic lesion, then pulmonary function testing must demonstrate vital capacity \<80% predicted, FEV1 \<80% predicted or DLCO, \<70% predicted, and condition is evaluable for treatment response and could not be explained through a diagnosis of asthma.)
• •* SS-LCH with multifocal bone or skin disease
• •* MS-LCH with or without involvement of 'risk organs'
• •4. Archival tumor available for central confirmation of LCH and biomarker analysis or willingness to undergo biopsy.
• •5. If 18 years or older, performance status score of 0, 1, and 2 according to the Eastern Cooperative Oncology Group (ECOG) scale. If age \>=12 and \<18, performance status score of \>50 according to the Karnofsky performance status (KPS) scale.
• •6. Able to swallow and retain oral medication.
• •7. Male subjects with a female partner of childbearing potential must have had a prior vasectomy or agree to use adequate contraception from the time of the first dose of study drug until three months after the last dose of study drug.
• •8. A female subject is eligible to participate if she is of:
• •* Non-childbearing potential (i.e., physiologically incapable of becoming pregnant) defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \> 40 MlU/mL and estradiol \< 40 pg/mL (\<140 pmol/L) is confirmatory\]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods defined in the protocol if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment. For most forms of HRT, at least two to four weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.
• •* Child-bearing potential, has a negative serum pregnancy test during the screening period, and agrees to use adequate contraception from screening until four weeks after the last dose of study drug.
• •Note: Oral contraceptives are not reliable due to potential drug-drug interaction.
• •9. Adequate organ-systems function.