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

Related Clinical Trial
Combination Chemotherapy and Dasatinib in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia Decitabine as Maintenance Therapy After Standard Therapy in Treating Patients With Previously Untreated Acute Myeloid Leukemia Donor Stem Cell Transplant in Treating Patients With Acute Myeloid Leukemia in Remission S0432 Tipifarnib in Treating Older Patients With Acute Myeloid Leukemia Reduced Intensity Donor Peripheral Blood Stem Cell Transplant in Treating Patients With De Novo or Secondary Acute Myeloid Leukemia in Remission Combination Chemotherapy With or Without Valspodar in Treating Patients With Previously Untreated Acute Myeloid Leukemia Tipifarnib in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Tipifarnib and Etoposide in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia Alvocidib, Cytarabine, and Mitoxantrone in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia Bortezomib, Daunorubicin, and Cytarabine in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia Vorinostat and Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia Comparing Three Different Combination Chemotherapy Regimens in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Tipifarnib and Etoposide in Treating Older Patients With Newly Diagnosed, Previously Untreated Acute Myeloid Leukemia Flavopiridol, Cytarabine, and Mitoxantrone in Treating Patients With Relapsed or Refractory Acute Leukemia AKT Inhibitor MK-2206 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Early Discharge and Outpatients Care in Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia Previously Treated With Intensive Chemotherapy Bortezomib, Mitoxantrone, Etoposide, and Cytarabine in Relapsed or Refractory Acute Myeloid Leukemia Vorinostat, Azacitidine, and Gemtuzumab Ozogamicin for Older Patients With Relapsed or Refractory AML Trebananib With or Without Low-Dose Cytarabine in Treating Patients With Acute Myeloid Leukemia Cholecalciferol in Treating Patients With Acute Myeloid Leukemia Undergoing Intensive Induction Chemotherapy Alvocidib, Cytarabine, and Mitoxantrone Hydrochloride or Cytarabine and Daunorubicin Hydrochloride in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia Cyclosporine, Pravastatin Sodium, Etoposide, and Mitoxantrone Hydrochloride in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Metformin+Cytarabine for the Treatment of Relapsed/Refractory AML Arsenic Trioxide in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Sirolimus, Idarubicin, and Cytarabine in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia Lithium Carbonate and Tretinoin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Ixazomib (MLN9708) in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Omacetaxine Mepesuccinate, Cytarabine, and Decitabine in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia CPX-351 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome Lenalidomide and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Choline Magnesium Trisalicylate and Combination Chemotherapy in Treating Patients With Acute Myeloid Leukemia AML Therapy With Irradiated Allogeneic Cells Decitabine, Cytarabine, and Daunorubicin Hydrochloride in Treating Patients With Acute Myeloid Leukemia Busulfan, Fludarabine Phosphate, and Anti-Thymocyte Globulin Followed By Donor Stem Cell Transplant and Azacitidine in Treating Patients With High-Risk Myelodysplastic Syndrome and Older Patients With Acute Myeloid Leukemia Azacitidine and Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia Tipifarnib in Treating Patients With Acute Myeloid Leukemia in Remission Genetic and Molecular Characteristics of Mexican Adults With Acute Myeloid Leukemia: a Prospective Multicentric Study. Cytarabine With or Without SCH 900776 in Treating Adult Patients With Relapsed Acute Myeloid Leukemia Tipifarnib in Treating Older Patients With Acute Myeloid Leukemia Studying Biomarkers in Samples From Younger Patients With Acute Myeloid Leukemia Central Nervous System (CNS) Involvement in Acute Myeloid Leukemia (AML)

Brief Title

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

Official Title

A Phase 2 Study of the AKT Kinase Inhibitor MK-2206 in Patients With Relapsed Refractory Acute Myelogenous Leukemia

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 cells by blocking some of the enzymes needed for cell growth.
    

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
      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.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Number of Participants With a Response of CR, CRp, or PR

Secondary Outcome

 Maximum Percentage Change in Apoptosis

Condition

Adult Acute Megakaryoblastic Leukemia (M7)

Intervention

Akt inhibitor MK2206

Study Arms / Comparison Groups

 Treatment (Akt inhibitor MK2206)
Description:  Akt inhibitor MK2206 200 mg orally once a week for each 28 day treatment cycle

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

19

Start Date

October 2010

Completion Date

April 2014

Primary Completion Date

October 2013

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
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Marina Konopleva, MD, PHD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT01253447

Organization ID

NCI-2010-02186

Secondary IDs

NCI-2010-02186

Responsible Party

Sponsor

Study Sponsor

National Cancer Institute (NCI)


Study Sponsor

Marina Konopleva, MD, PHD, Principal Investigator, UT MD Anderson Cancer Center


Verification Date

July 2018