A Phase I, Open-Label, Two-Stage Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Oral AKT Inhibitor GSK2110183 in Subjects With Any Hematologic Malignancy
1. Written informed consent is provided.
2. Male or female who is at least 18 years of age or older.
3. Histologically- or cytologically-confirmed diagnosis of a hematologic malignancy -
that has relapsed or is refractory after standard therapy, AND that is not associated
with human immunodeficiency virus (HIV) infection or solid organ transplant,
- chronic lymphocytic leukemia (CLL),
- chronic myelogenous leukemia (CML),
- multiple myeloma (MM),
- non-Hodgkin's lymphoma (NHL),
- Hodgkin's lymphoma, or
- Other hematologic malignancy excluding:
- acute leukemia of any type
- CML blast crisis
- myelodysplastic syndrome (MDS)
4. Performance Status score of 0 and 1 according to the Eastern Cooperative Oncology
Group (ECOG) scale
5. Able to swallow and retain oral medication.
6. Fasting serum glucose < 126 mg/dL (<7 mmol/L).
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
- 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.
9. Adequate organ system function
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.
2. Use of an investigational anti-cancer drug within 28 days or five half-lives,
whichever is longer, preceding the first dose of study drug.
3. Current use of a prohibited medication or requires any of these medications during
treatment with study drug.
4. Current use of anticoagulants at therapeutic levels within seven days prior to the
first dose of study drug, including warfarin, low molecular weight heparin and direct
thrombin inhibitors. Low dose (prophylactic) anticoagulants are permitted provided
that subject's PT and PTT meet entry criteria.
5. Current use of any anti-platelet agent (e.g. dipyridamole, clopidogrel) other than
aspirin (81 mg daily).
6. Presence of active gastrointestinal disease or other condition that could affect
gastrointestinal absorption (e.g. malabsorption syndrome) or predispose subject to
7. Any major surgery within the last four weeks.
8. Unresolved toxicity (except alopecia) Grade 2 from previous anti-cancer therapy
unless agreed to by a Medical Monitor and the Investigator
9. Previously diagnosed diabetes mellitus (Type 1 or 2).
10. Current use of oral corticosteroids, with the exception of inhaled or topical
11. 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.
12. Symptomatic or untreated central nervous system (CNS) involvement by the hematologic
malignancy (including primary CNS lymphoma).
13. Evidence of severe or uncontrolled systemic diseases
14. Known infection with HIV, HBV or HCV.
15. QTc interval ≥ 470 msecs.
16. Other clinically significant ECG abnormalities including 2nd degree (Type II) or 3rd
degree atrioventricular (AV) block.
17. History of myocardial infarction, acute coronary syndromes (including unstable
angina), coronary angioplasty, or stenting or bypass grafting within the past six
18. Class III or IV heart failure as defined by the New York Heart Association (NYHA)
functional classification system.
19. Pregnant or lactating female.
20. Active drug or alcohol abuse.
21. History of sensitivity to heparin or heparin-induced thrombocytopenia.