AKT Inhibitor MK-2206 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia
Condition: Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Monocytic, Acute; Leukemia, Myelomonocytic, Acute; Leukemia, Megakaryoblastic, Acute; Leukemia, Erythroblastic, Acute
Intervention: Akt inhibitor MK2206; laboratory biomarker analysis
Intervention description: 200 mg orally (PO) once weekly. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.; Correlative studies
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 19.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well AKT inhibitor MK-2206 works in treating patients
      with relapsed or refractory acute myeloid leukemia (AML). AKT inhibitor MK-2206 may stop the
      growth of cancer cells by blocking some of the enzymes needed for cell growth.
    

Eligibility criteria:

        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