Trametinib and Akt Inhibitor GSK2141795 in Treating Patients With Acute Myeloid Leukemia

Exclusion Criteria

• •History of another malignancy; exception: patients who have been disease-free for 3 years, or patients with a history of completely resected non-melanoma skin cancer and/or patients with indolent secondary malignancies, are eligible; consult the Cancer Therapy Evaluation Program (CTEP) Medical Monitor if unsure whether second malignancies meet the requirements specified above
• •History of interstitial lung disease or pneumonitis
• •Any major surgery, extensive radiotherapy, chemotherapy with delayed toxicity, biologic therapy, or immunotherapy within 21 days prior to randomization; daily or weekly chemotherapy (with the exception of hydroxyurea) without the potential for delayed toxicity within 14 days prior to randomization unless there is evidence of rapidly progressive disease
• •Use of other investigational drugs within 28 days (or five half-lives, whichever is shorter; with a minimum of 14 days from the last dose) preceding the first dose of trametinib/GSK2141795 and during the study
• •Symptomatic or untreated leptomeningeal disease or brain metastases or spinal cord compression
• •Patients with abnormal fasting glucose values (\> 150 mg/dl) at screening will be excluded; in addition, patients with type 1 diabetes will also be excluded; however, patients with type 2 diabetes will be allowed if diagnosed \>= 6 months prior to enrollment, and if presenting with regular hemoglobin A1C (HbA1C) =\< 8% at screening
• •Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to trametinib or excipients or to dimethyl sulfoxide (DMSO) or GSK2141795
• •Current use of a prohibited medication; the following medications or non-drug therapies are prohibited:
• •* Other anti-cancer therapy while on study treatment; (Note: megestrol \[Megace\] if used as an appetite stimulant is allowed)
• •* Concurrent treatment with bisphosphonates is permitted; however, treatment must be initiated prior to the first dose of study therapy; prophylactic use of bisphosphonates in patients without bone disease is not permitted, except for the treatment of osteoporosis
• •* The concurrent use of all herbal supplements is prohibited during the study (including, but not limited to, St. John's wort, kava, ephedra \[ma huang\], gingko biloba, dehydroepiandrosterone \[DHEA\], yohimbe, saw palmetto, or ginseng)
• •* Note: for proliferative disease, hydroxyurea will be allowed during weeks 1 and 2 of cycle 1 of study; hydroxyurea may be started or the dose changed during that 2-week period if it is clinically indicated; if a subject not previously on a stable dose of hydroxyurea needs to begin hydroxyurea or a subject on a stable dose needs to have their dose increased during the first 2 weeks, the investigator will notify the clinical team that this has been initiated
• •Drugs that potently inhibit cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) should either be prohibited or used with caution; drugs which are strong inducers of cytochrome P450 family 3, subfamily A (CYP3A) should also be prohibited; drugs that are substrates of CYP3A4 or cytochrome P450 family 2, subfamily C, polypeptide 8 (CYP2C8) with a narrow therapeutic index may be prohibited; drugs that are sensitive substrates of CYP3A4 or CYP2C8 should be used with caution; it is important to regularly consult a frequently-updated list; medical reference texts such as the Physicians' Desk Reference may also provide this information; as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
• •History or current evidence/risk of retinal vein occlusion (RVO)
• •History or evidence of cardiovascular risk including any of the following:
• •* LVEF \< institutional LLN or \< 50%
• •* A QT interval corrected for heart rate using the Bazett's formula QTcB \>= 480 msec
• •* History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for \> 30 days prior to randomization are eligible)
• •* History or evidence of current clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for \> 30 days prior to study dose are eligible)
• •* Patient with symptomatic bradycardia, or a history of clinically significant bradyarrhythmias such as sick sinus syndrome, second (2nd) degree atrioventricular (AV) block (Mobitz type 2)
• •* History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to study dose
• •* History or evidence of current \>= class II congestive heart failure as defined by the New York Heart Association (NYHA) functional classification system
• •* Treatment-refractory hypertension defined as a blood pressure of systolic \> 140 mmHg and/or diastolic \> 90 mmHg which cannot be controlled by anti-hypertensive therapy
• •* Patients with intra-cardiac defibrillators
• •* Known cardiac metastases