A Phase I Open-Label Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Potential Anti-Cancer Activity of the AKT Inhibitor GSK690693 in Subjects With Relapsed or Refractory Hematologic Malignancies
- 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.
- Signed written consent provided.
- At least 18 years of age.
- A woman is eligible to enter and participate in the study if she is of:
Non-childbearing potential , or is post-menopausal .
- A man with a female partner of childbearing potential is eligible to enter and
participate in the study if he has either had a prior vasectomy or agrees to use
adequate contraception (as described above) during the study, and up to 3 months
after last dose of study drug.
- Fasting glucose that is not elevated.
- Laboratory values within ranges defined in the protocol
- Previously diagnosed diabetes mellitus (type 1 or 2), or gestational diabetes.
- Symptomatic or untreated central nervous system (CNS) involvement by the hematologic
malignancy (including primary CNS lymphoma). Subjects who were previously treated
for CNS involvement, and are asymptomatic without anti-epileptic medications or
steroids for at least 2 months are eligible.
- Subjects who have undergone an allogeneic stem cell transplant.
- Unresolved toxicity from previous anti-cancer therapy as agreed to by Medical Monitor
and the Investigator,.
- Major surgery within the past 28 days.
- Chemotherapy, radiotherapy, immunotherapy, or investigational drug therapy within 21
days (or 42 days for prior nitrosoureas or mitomycin C) prior to the first dose of
study medication. For subjects with acute leukemia, anti-cancer chemotherapy
(including corticosteroids) may be administered up to 7 days prior to the first dose
of study medication. Chemotherapy given at a dose and schedule that is not expected
to have delayed toxicity can be given with an interval of 14 days or more from the
first dose. Hydroxyurea may be administered up to 7 days prior to the first dose of
- Current use of oral corticosteroids, with the exception of inhaled or topical
- Evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated
respiratory, hepatic, or renal disease).
- Any female who is pregnant or lactating.
- 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.
- Significant ECG abnormalities.
- Use of medications known to prolong the QTc interval within 14 days (or 5 half-lives)
prior to the first dose of study medication.
- History of myocardial infarction, acute coronary syndromes, unstable angina or
coronary angioplasty/stenting/bypass grafting within the past 6 months.
- Left ventricular ejection fraction (LVEF) less than 50% by echocardiogram (ECHO) or
multiple gated acquisition (MUGA) scanning.
- Use of theophylline within 14 days of the first dose of study medication.
- Current use of warfarin ≥4 mg per day; however, low molecular weight heparin and
prophylactic low-dose warfarin are permitted, if PT/PTT < 1.2 x ULN.
- Concurrent condition that in the Investigator's opinion would jeopardize the
subject's ability to comply with the protocol.
- History of allergic reactions attributed to compounds of similar chemical composition