A Phase 2a, Open Label, Multicenter Study to Assess the Efficacy and Safety of the Oral AKT Inhibitor GSK2110183 in Subjects With 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.

Exclusion Criteria:

1. Chemotherapy, radiotherapy, or immunotherapy within 28 days (or 42 days for prior
nitrosoureas or mitomycin C) prior to the first dose of study drug. Corticosteroids
may be administered up to seven days prior to the first dose of study drug.
Chemotherapy regimens given continuously or on a weekly basis with limited potential
for delayed toxicity (in the medical opinion of the investigator) are permitted, if
administered at least 14 days prior to the first dose of study drug.

2. Use of an investigational anti-cancer drug within 28 days or five half-lives,
whichever is longer, preceding the first dose of GSK2110183.

3. Current use of a prohibited medication or requires any of these medications during
treatment with GSK2110183.

4. Presence of active gastrointestinal disease or other condition that could affect
gastrointestinal absorption (e.g. malabsorption syndrome) or predispose subject to
gastrointestinal ulceration.

5. Any major surgery within the last four weeks (excluding diagnostic biopsy).

6. Unresolved toxicity (except alopecia) >= Grade 2 from previous therapy, except where
the Investigator considers that the ongoing toxicity will not introduce additional
risk factors and will not interfere with the study procedures.

7. Fasting serum glucose >126 mg/dL (7 mmol/L), or for known diabetic patients with
stable disease, fasting serum glucose >250 mg/dL (14 mmol/L) and Hemoglobin A1c > 9%.

8. Current use of oral corticosteroids, with the exception of stress dose hydrocortisone
(20 mg BID). Inhaled steroids permitted if patient is currently on a stable
dose/regimen. Topical steroids are permitted; however, they should not be used as
concurrent treatment for LCH skin disease.

9. Any serious or unstable pre-existing medical, psychiatric, or other condition
(including lab abnormalities) that could interfere with subject safety or with
obtaining informed consent.

10. Evidence of LCH-related neurodegenerative disease if patient has CNS SS-LCH, however,
subjects with CNS SS-LCH who were previously treated for CNS involvement, and are
currently asymptomatic without anti-epileptic medications or steroids for at least
two months are eligible.

11. Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated
respiratory, hepatic, renal, or cardiac disease).

12. Known infection with HIV, HBV or HCV.

13. QTc interval >= 470 msecs.

14. History of myocardial infarction, acute coronary syndromes (including unstable
angina), coronary angioplasty, or stenting or bypass grafting within the past six
months.

15. Class III or IV heart failure as defined by the New York Heart Association (NYHA)
functional classification system.

16. Pregnant or lactating female.

17. History of previous treatment with a small molecule AKT inhibitor (this does not
include perifosine), PI3K inhibitors, or mTOR inhibitors.

18. Other associated conditions which in the opinion of the investigator could
significantly impair the ability to evaluate the impact of treatment on the clinical
course of the disease.