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

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ClinicalTrials.gov Identifier: NCT01253447
Recruitment Status : Completed
First Posted : December 3, 2010
Results First Posted : January 7, 2015
Last Update Posted : August 27, 2018
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions 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
Interventions Drug: Akt inhibitor MK2206
Other: laboratory biomarker analysis
Enrollment 19
Recruitment Details Recruitment Period: October 27, 2010 to October 30, 2012. All recruitment done in medical clinics, either UT MD Anderson Cancer Center or Fred Hutchinson Cancer Research Center.
Pre-assignment Details  
Arm/Group Title Treatment (Akt Inhibitor MK2206)
Hide Arm/Group Description Akt inhibitor MK2206 200 mg orally once a week for each 28 day treatment cycle
Period Title: Overall Study
Started 19
Completed 17
Not Completed 2
Reason Not Completed
Adverse Event             2
Arm/Group Title Treatment (Akt Inhibitor MK2206)
Hide Arm/Group Description Akt inhibitor MK2206 200 mg orally once a week for each 28 day treatment cycle
Overall Number of Baseline Participants 19
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 19 participants
72
(31 to 86)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants
Female
7
  36.8%
Male
12
  63.2%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants
American Indian or Alaska Native
0
   0.0%
Asian
1
   5.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
1
   5.3%
White
16
  84.2%
More than one race
0
   0.0%
Unknown or Not Reported
1
   5.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 19 participants
19
1.Primary Outcome
Title Number of Participants With a Response of CR, CRp, or PR
Hide Description Responses defined by International Working Group (IWG) 2003 Response Criteria: Morphologic Complete Response (CR): Peripheral blood counts: No circulating blasts, Neutrophil count >/= 1.0 x10^9/L, Platelet count >/= 100 x10^9/L; Bone marrow aspirate and biopsy: </= 5% blasts, No detectable Auer rods, No extramedullary leukemia. Partial Response (PR): No circulating blasts, Neutrophil count >/=1.0 x10^9/L, Platelet count >/= 100 x10^9/L, >/= 50 % reduction in bone marrow blast to 6% to 25%, or blasts </= 5% if Auer rods are present. Morphologic CR with incomplete count recovery (CRp): All criteria for CR except for residual neutropenia (<1x10^9/L) or thrombocytopenia (<100 x10^9/L).
Time Frame 12 weeks of treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
No participant was not evaluable for response.
Arm/Group Title Treatment (Akt Inhibitor MK2206)
Hide Arm/Group Description:
Akt inhibitor MK2206 200 mg orally once a week for each 28 day treatment cycle
Overall Number of Participants Analyzed 18
Measure Type: Number
Unit of Measure: participants
CR 0
CRp 1
PR 0
2.Primary Outcome
Title Number of Participants With Treatment-related Non-hematological Toxicity
Hide Description Toxicity assessed using the NIH-NCI Common Terminology Criteria for Adverse Events, version 4.0 (CTCAEv4.0)
Time Frame Up to 30 days post-treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Akt Inhibitor MK2206)
Hide Arm/Group Description:

Akt inhibitor MK2206 200 mg orally once a week for each 28 day treatment cycle

Akt inhibitor MK2206: 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.

laboratory biomarker analysis: Correlative studies

Overall Number of Participants Analyzed 18
Measure Type: Count of Participants
Unit of Measure: Participants
Neutropenic Fever
2
  11.1%
Documented infection
6
  33.3%
Pneumonia
2
  11.1%
Fever of Unknown Origin
2
  11.1%
QTc Prolongation
4
  22.2%
Maculopapular Rash
10
  55.6%
Hyperglycemia
12
  66.7%
Posterior reversible encephalopathy (PRES Syndrome
1
   5.6%
3.Secondary Outcome
Title Maximum Percentage Change in Apoptosis
Hide Description Peripheral blood Acute Myeloid Leukemia (AML) cells (total 2 x 10^6) used to determine induction of apoptosis in AML stem cells by 4-color flow cytometry assay (CD34/CD38/CD123/annexin). Two-sample t-test conducted to compare changes between the responders and non-responders. Responders are participants who obtain a CR, CRp, or PR, with or without cytogenetic response.
Time Frame Baseline to 12 courses
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The Assay did not work so no comparison can be made.
Arm/Group Title Treatment (Akt Inhibitor MK2206)
Hide Arm/Group Description:
Akt inhibitor MK2206 200 mg orally once a week for each 28 day treatment cycle
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Participants followed for up to a total of 12 cycles (up to 36 weeks), with serious adverse events captured from consent until 30 days after last dose of drug. Overall adverse events were collected from January 26, 2011 to October 22, 2012.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Treatment (Akt Inhibitor MK2206)
Hide Arm/Group Description Akt inhibitor MK2206 200 mg orally once a week for each 28 day treatment cycle
All-Cause Mortality
Treatment (Akt Inhibitor MK2206)
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Treatment (Akt Inhibitor MK2206)
Affected / at Risk (%) # Events
Total   12/19 (63.16%)    
Blood and lymphatic system disorders   
Leukocytosis  2  1/19 (5.26%)  1
Neutrophil count decreased  2  1/19 (5.26%)  1
Platelet count decreased  2  1/19 (5.26%)  1
Cardiac disorders   
Myocardial infarction  2  1/19 (5.26%)  1
General disorders   
Fatigue  2  3/19 (15.79%)  3
Infections and infestations   
Anorectal infection  1  1/19 (5.26%)  1
Febrile neutropenia  2  5/19 (26.32%)  6
Infections  2 [1]  2/19 (10.53%)  2
Sepsis  2  3/19 (15.79%)  3
Soft Tissue Infection (cellulitis)  2  1/19 (5.26%)  1
Investigations   
Pain in extremity  2  1/19 (5.26%)  1
Metabolism and nutrition disorders   
Hyperglycemia  2  5/19 (26.32%)  6
Hyperkalemia  2  1/19 (5.26%)  1
Hypertension  2  1/19 (5.26%)  1
Musculoskeletal and connective tissue disorders   
Back pain  2  1/19 (5.26%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Neoplasms  2 [2]  1/19 (5.26%)  1
Nervous system disorders   
Reversible posterior leukoencephalopathy syndrome  2  1/19 (5.26%)  1
Respiratory, thoracic and mediastinal disorders   
Hypoxia  2  1/19 (5.26%)  1
Lung infection  2  1/19 (5.26%)  1
Bilateral carck in lungs  2  1/19 (5.26%)  1
Skin and subcutaneous tissue disorders   
Pruritus  2  1/19 (5.26%)  1
Rash acneiform  2  1/19 (5.26%)  1
Rash maculo-papular  2  4/19 (21.05%)  4
Mucor fungal infection  2  1/19 (5.26%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
2
Term from vocabulary, CTCAE (4.0)
[1]
Lung, Sepsis
[2]
Symptoms skin lesions
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Treatment (Akt Inhibitor MK2206)
Affected / at Risk (%) # Events
Total   19/19 (100.00%)    
Blood and lymphatic system disorders   
Edema limbs  1  3/19 (15.79%)  3
Cardiac disorders   
Electrocardiogram QT corrected interval prolonged  1  1/19 (5.26%)  1
Sinus tachycardia  1  1/19 (5.26%)  1
Ear and labyrinth disorders   
Hearing impaired  1  1/19 (5.26%)  1
Endocrine disorders   
Hidradenitis  1  1/19 (5.26%)  1
Eye disorders   
Periorbital edema  1  1/19 (5.26%)  1
Gastrointestinal disorders   
Anorexia  1  2/19 (10.53%)  2
Diarrhea  1  10/19 (52.63%)  11
Poor Appetitue, Gastrointestinal  1  1/19 (5.26%)  1
Hemorrhoids  1  1/19 (5.26%)  1
Mucositis oral  1  2/19 (10.53%)  2
Nausea  1  2/19 (10.53%)  2
Oral hemorrhage  1  1/19 (5.26%)  1
Sore throat  1  1/19 (5.26%)  1
Vomiting  1  2/19 (10.53%)  2
General disorders   
Epistaxis  1  3/19 (15.79%)  3
Fatigue  1  8/19 (42.11%)  8
Infections and infestations   
Throat Yeast infection  1  1/19 (5.26%)  1
Injury, poisoning and procedural complications   
Fall  1  1/19 (5.26%)  1
Investigations   
Chills  1  1/19 (5.26%)  1
Fever  1  3/19 (15.79%)  3
Pancytopenia  1  1/19 (5.26%)  1
Metabolism and nutrition disorders   
Creatinine increased  1  1/19 (5.26%)  1
Hyperglycemia  1  13/19 (68.42%)  26
Hypokalemia  1  1/19 (5.26%)  1
Musculoskeletal and connective tissue disorders   
Arthralgia  1  1/19 (5.26%)  1
Back Pain  1  1/19 (5.26%)  1
Bone Pain  1  1/19 (5.26%)  1
Gait disturbance  1  1/19 (5.26%)  1
Generalized muscle weakness  1  1/19 (5.26%)  1
Pain  1  2/19 (10.53%)  5
Nervous system disorders   
Dizziness  1  1/19 (5.26%)  1
Headache  1  3/19 (15.79%)  3
Intracranial hemorrhage  1  1/19 (5.26%)  1
Tremor  1  1/19 (5.26%)  1
Psychiatric disorders   
Anxiety  1  1/19 (5.26%)  1
Depression  1  1/19 (5.26%)  1
Insomnia  1  2/19 (10.53%)  2
Irritability  1  1/19 (5.26%)  1
Renal and urinary disorders   
Hematuria  1  1/19 (5.26%)  1
acute renal insufficiency, elevated creatinine  1  1/19 (5.26%)  1
Urinary frequency  1  1/19 (5.26%)  1
Urinary tract pain  1  1/19 (5.26%)  1
Respiratory, thoracic and mediastinal disorders   
Cough  1  4/19 (21.05%)  4
Dyspnea  1  10/19 (52.63%)  11
Laryngitis  1  1/19 (5.26%)  1
Skin and subcutaneous tissue disorders   
Bruising  1  2/19 (10.53%)  2
Dry skin  1  1/19 (5.26%)  1
Flushing  1  1/19 (5.26%)  1
Hyperhidrosis  1  1/19 (5.26%)  1
Pruritus  1  4/19 (21.05%)  4
Rash maculo-papular  1  5/19 (26.32%)  6
Night Sweats  1  1/19 (5.26%)  1
Petechiae  1  1/19 (5.26%)  1
Skin ulceration  1  3/19 (15.79%)  3
Leukemia Cutis  1  1/19 (5.26%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (4.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Marina Konopleva, MD, PHD / Professor
Organization: The University of Texas (UT) MD Anderson Cancer Center
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01253447     History of Changes
Obsolete Identifiers: NCT01654978
Other Study ID Numbers: NCI-2010-02186
NCI-2010-02186 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2010-0243 ( Other Identifier: M D Anderson Cancer Center )
8731 ( Other Identifier: CTEP )
N01CM00039 ( U.S. NIH Grant/Contract )
First Submitted: December 1, 2010
First Posted: December 3, 2010
Results First Submitted: December 23, 2014
Results First Posted: January 7, 2015
Last Update Posted: August 27, 2018