GSK200200 - LSD1: This phase I trial is assessing an oral drug (GSK2879552) in patients with relapsed Acute Myeloid Leukaemia (AML)A Phase I Open-label, Dose Escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of GSK2879552 Given Orally in Subjects With Relapsed/Refractory Acute Myeloid Leukemia

Exclusion

• 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.