AKT Inhibitor MK-2206 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed AML other than acute promyelocytic leukemia (2008 WHO classification)
• Patients must have persistent or relapsing disease requiring 2nd salvage therapy (e.g. treatment for second or higher relapse or for primary refractory disease after failure of two prior treatment regimens); duration of prior complete remission < 12 months if not refractory disease; patients with prior autologous and allogeneic hematopoietic stem cell transplantation are eligible if patients are off immunosuppression for >1 month and have no evidence of active graft versus host disease (GVHD) except grade 1 skin GVHD
• Patients age >= 60 years with less than two prior treatment regimens not candidates for or have refused standard chemotherapy, excluding subjects with acute promyelocytic leukemia (APL) or with favorable cytogenetic abnormalities [inv16, t(8;21)]
• Patient at the time of enrollment should not be a candidate for allogeneic stem cell transplantation
• ECOG performance status =< 2
• Serum creatinine or calculated creatinine clearance =< 1.5 x upper limit of normal (ULN) OR >= 60 mL/min for patients with creatinine levels > 1.5 x institutional ULN
• Serum total bilirubin =< 2 x ULN OR direct bilirubin =< ULN for patients with total bilirubin levels > 2 x ULN, unless elevation is thought to be due to hepatic infiltration by AML, Gilbert‟s syndrome, or hemolysis
• AST (SGOT) and ALT (SGPT) =< 2.5 x ULN or =< 5 x ULN unless considered to be secondary to leukemic involvement
• Fasting serum glucose =< 150 mg/dl
• HBA1c =< 9%
• Female patient of childbearing potential must have a negative serum or urine pregnancy test beta-hCG within 72 hours prior to receiving the first dose of study medication; the effects of MK-2206 on the developing human fetus at the recommended therapeutic dose are unknown; for this reason women of childbearing potential and men must use two forms of contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, the patient should inform the treatment physician immediately
• Patient, or the patient‟s legal representative, has voluntarily agreed to participate by giving written informed consent
• Patient is able to swallow tablets and has no surgical or anatomical condition that will preclude the patient from swallowing and absorbing oral medications on an ongoing basis

Exclusion Criteria:

• Patients may not be receiving any other investigational agents
• Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1, without complete recovery
• Active uncontrolled infection
• Systemic chemotherapy (with the exception of hydroxyurea) within 14 days (or within 5 half-lives for an investigational agent) prior to first dose of study drug, unless there is evidence of rapidly progressive disease; persistent chronic clinically significant toxicities from prior chemotherapy must not be > grade 1
• Patients with CNS involvement
• Patient has known hypersensitivity to the components of study drug or its analogs
• Uncontrolled congestive heart failure, unstable angina pectoris
• Uncontrolled cardiac arrhythmia
• History or current evidence of a myocardial infarction during the last 6 months
• QTc prolongation > 450 msec (Bazett's Formula)
• Congenitally long QT syndrome, has received any marketed or experimental compound in the last 4 weeks or 5 half lives (whichever is shorter) prior to entering the study with possible or known effects of QT prolongation
• Patient with symptomatic bradycardia, or a history of clinically significant bradyarrhythmias such as sick sinus syndrome, 2nd degree AV block (Mobitz Type 2)
• Patient with uncontrolled hypertension (i.e., i.e., sustained systolic blood pressure >= 160 or diastolic >= 90); patients who are controlled on antihypertensive medication will be allowed to enter the study
• Patient with poorly controlled diabetes defined as HBA1C > 9%
• Patient is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study
• Patient is known to be Human Immunodeficiency Virus (HIV)-positive with history of AIDS defining conditions; or CD4 cells prior to leukemia onset =< 400 cells/mm^3; or patients receiving antiretroviral therapy that affects CYP3A4 such as protease inhibitors, efavirenz, nevirapine, or zidovudine
• Patient has active Hepatitis B or C or active Hepatitis A