A Phase I Dose Escalation Study of GSK2879552 in Subjects With Acute Myeloid Leukemia (AML)

Inclusion Criteria:

- Subjects >=18 years of age and provided signed written informed consent.

- Subjects must have relapsed/refractory AML by world health organization (WHO)
classification for which no standard therapies are available or anticipated to result
in a durable remission. French- American- British system (FAB) subtype M3 will be
excluded.

- Subjects >= 60 years of age with AML who are not candidates for or have refused
standard chemotherapy.

- Subjects who have previously received an autologous stem cell transplant are allowed
if a minimum of 3 months has elapsed from the time of transplant and the subject has
recovered from transplant-associated toxicities prior to the first dose of GSK2879552.

- Subjects with a history of allogeneic stem cell transplant are eligible for study
participation provided the following eligibility criteria are met: transplant was >60
days prior to study enrolment; subject has not taken immunosuppressive medications for
at least 1 month; no signs or symptoms of graft versus host disease other than Grade 1
skin involvement; no active infection.

- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

- Subjects must be stable and, in the opinion of the investigator, be expected to
complete 4 week treatment period.

- Able to swallow and retain orally administered medication and does not have any
clinically significant gastrointestinal abnormalities that may alter absorption such
as malabsorption syndrome or major resection of the stomach or bowels.

- All prior treatment-related toxicities must be National Cancer Institute- Common
Toxicity Criteria for Adverse Events (NCI-CTCAE), version 4.0 <=Grade 1 at the time of
enrollment (except for alopecia).

- Adequate baseline organ function.

- Women of childbearing potential must have a negative serum pregnancy test within 7
days of first dose of study treatment and agree to use effective contraception, during
the study and for 7 days (GSK2879552 mono therapy) or 30 days (combination with ATRA),
following the last dose of study treatment.

- Men with a female partner of childbearing potential must have either had a prior
vasectomy or agree to use effective contraception from the administration of the first
dose of study treatment until 3 months after the last dose of study treatment to allow
for clearance of any altered sperm.

Exclusion Criteria:

- Active human immunodeficiency virus (HIV), Hepatitis B Virus (HBV) or hepatitis C
virus (HCV) infections at the time of screening. Subjects with laboratory evidence of
HCV clearance may be enrolled.

- History of or concurrent malignancy of solid tumours, except: subjects who have been
disease-free for 5 years, or subjects with a history of completely resected
non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.
Subjects with second malignancies that are indolent or definitively treated may be
enrolled even if less than 5 years have elapsed since treatment. Consult
GlaxoSmithKline (GSK) Medical Monitor if unsure whether second malignancies meet
requirements specified above.

- Currently receiving cancer therapy. Hydroxyurea will be allowed.

- Received major surgery, radiotherapy, or immunotherapy within 4 weeks of GSK2879552
administration.

- Prior treatment with temozolomide, dacarbazine or procarbazine

- Prior treatment with poly ADP ribose polymerase (PARP) inhibitors (eg., olaparib,
ABT-888)

- Baseline Montreal Cognitive Assessment (MOCA) score of 22 or lower

- Evidence of severe or uncontrolled systemic diseases. Any serious and/or unstable
pre-existing medical, psychiatric disorder, or other conditions that could interfere
with subject's safety, obtaining informed consent or compliance to the study
procedures, in the opinion of the Investigator

- Current active liver or biliary disease.

- Patients at risk of non-AML related major bleeding (e.g. recent gastrointestinal [GI]
hemorrhage or neurosurgery).

- Symptomatic or untreated central nervous system (CNS) leukemia. Subjects are permitted
to enroll if previously treated for CNS disease, free of symptoms at the time of
screening, and have not required intrathecal chemotherapy at least 1 month prior to
study Day 1.

- Cardiac abnormalities

- Administration of an investigational drug within 14 days or 5 half-lives, whichever is
shorter with a minimum of 14 days preceding the first dose of study treatment(s) in
this study.

- Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to GSK2879552 or LSD1 inhibitors that contraindicates their
participation.

- Lactating female.

- Consumption of Seville oranges, grapefruit, grapefruit hybrids, grapefruit juice,
pommelos, or exotic citrus fruits, from 1 day prior to the first dose of study
treatment(s) until the last dose of study drug.

- Current use of a prohibited medication including anticoagulants or platelet inhibitors
or expected to require any of these medications during treatment with the
investigational drug.

- Previous treatment with GSK2879552 For ATRA Combination arm ONLY

- Known hypersensitivity to ATRA, parabens (preservatives in the gelatin capsule) or
other retinoids.

- ATRA capsule contains sorbitol. Subjects with rare hereditary problems of fructose
intolerance are excluded.

- History of seizure within 12 months or brain tumor (primary)

- History of taking mega-dose vitamin A (>25,000 USP U/day) within 3 months from the
dosing start.