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

PRIMARY OBJECTIVES:

I. Determine the proportion of patients achieving Morphologic Complete Response (CR),
Morphologic CR with incomplete count recovery (CRp) or Partial Response (PR) as best response
within 3 cycles of therapy with MK-2206.

SECONDARY OBJECTIVES:

I. Describe the disease-free survival of patients that achieve CR/CRp.

II. Determine the toxicity profile of single-agent MK-2206 in this patient population.

III. To determine the biologic effects of MK-2206 on leukemia cells.

OUTLINE:

Patients receive AKT inhibitor MK-2206 orally (PO) once weekly. Treatment repeats every 28
days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Inclusion Criteria:

- Patients must have histologically or cytologically confirmed AML other than acute
promyelocytic leukemia (2008 World Health Organization (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

- The Eastern Cooperative Oncology Group (ECOG) performance status =< 2

- Serum creatinine or calculated creatinine clearance =< 1.5 * upper limit of normal
(ULN) OR >= 60 mL/min for patients with creatinine levels > 1.5 * institutional ULN

- Serum total bilirubin =< 2 * ULN OR direct bilirubin =< ULN for patients with total
bilirubin levels > 2 * ULN, unless elevation is thought to be due to hepatic
infiltration by AML, Gilbert's syndrome, or hemolysis

- asparate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT /SGPT) =< 2.5 *
ULN or =< 5 * 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- Human chorionic gonadotropin (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 central nervous system (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

- corrected Q-T interval (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