Status:

COMPLETED

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

Lead Sponsor:

National Cancer Institute (NCI)

Conditions:

Adult Acute Megakaryoblastic Leukemia (M7)

Adult Acute Minimally Differentiated Myeloid Leukemia (M0)

Eligibility:

All Genders

18+ years

Phase:

PHASE2

Brief 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 ...

Detailed Description

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...

Eligibility Criteria

Inclusion

  • 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

  • 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

Key Trial Info

Start Date :

October 1 2010

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

April 1 2014

Estimated Enrollment :

19 Patients enrolled

Trial Details

Trial ID

NCT01253447

Start Date

October 1 2010

End Date

April 1 2014

Last Update

August 27 2018

Active Locations (2)

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Page 1 of 1 (2 locations)

1

UT MD Anderson Cancer Center

Houston, Texas, United States, 77030

2

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, United States, 98109