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

• Status: Completed
• Trial end date: 2014-04-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)

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