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Selumetinib in Treating Patients With Recurrent or Refractory Acute Myeloid Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00588809
Recruitment Status : Completed
First Posted : January 9, 2008
Results First Posted : August 5, 2015
Last Update Posted : August 5, 2015
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This phase II clinical trial is studying how well selumetinib works in treating patients with recurrent or refractory acute myeloid leukemia. Selumetinib may stop the growth of cancer by blocking some of the enzymes needed for cell growth

Condition or disease Intervention/treatment Phase
Adult Acute Myeloid Leukemia With t(15;17)(q22;q12) Adult Acute Promyelocytic Leukemia (M3) Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Neoplasms Recurrent Adult Acute Myeloid Leukemia Secondary Acute Myeloid Leukemia Drug: selumetinib Phase 2

Detailed Description:


I. To determine the response rate (includes complete response-CR, complete response with incomplete count recovery CRi, partial response-PR, and minor response-MR) to AZD6244 (selumetinib).


I. To determine the effects of AZD6244 in AML samples on p-ERK and evaluate the potential utility of p-ERK inhibition as a surrogate marker of biologic activity.

II. To correlate the effects of AZD6244 with the presence (or absence) of mutated RAS or FLT-3 at baseline.

III. To assess the safety profile of AZD6244 in patients with AML.


Patients receive selumetinib orally (PO) twice daily (BID) on days 1 -28. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for 52 weeks.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 47 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of AZD6244 in Relapsed or Refractory AML
Study Start Date : December 2007
Actual Primary Completion Date : April 2012
Actual Study Completion Date : December 2012

Arm Intervention/treatment
Experimental: Treatment (selumetinib)
Patients receive selumetinib PO BID on days 1 -28. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.
Drug: selumetinib
Given PO
Other Names:
  • ARRY-142886
  • AZD6244

Primary Outcome Measures :
  1. Response Rate for Subjects Without FLT3 ITD Mutation [ Time Frame: Up to 52 weeks ]

    Responses were defined using standard criteria developed by an International Working Group.

    [Cheson BD, Bennett JM, Kopecky KJ, Buchner T, Willman CL, Estey EH, et al. Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol 2003;21:4642-9.]

    In this primary outcome, we report the proportion of subjects without FLT3 ITD mutation that experienced a complete response (CR), partial response (PR), minor response (MR), or unconfirmed minor response (uMR).

Secondary Outcome Measures :
  1. Proportion of Subjects With Baseline p-ERK Activation [ Time Frame: baseline (0 weeks) ]
    Proportion of subjects with baseline p-ERK activation

  2. Proportion of Subjects With NRAS Mutation [ Time Frame: baseline (0 weeks) ]
    Proportion of Subjects With NRAS Mutation

  3. Proportion of Subjects With KRAS Mutation [ Time Frame: baseline (0 weeks) ]
    Proportion of subjects with KRAS mutation

  4. Proportion of Subjects With FLT3 ITD Mutation [ Time Frame: baseline (0 weeks) ]
    Proportion of subjects with FLT3 ITD mutation

  5. Proportion of Subjects With KIT Mutation [ Time Frame: baseline (0 weeks) ]
    Proportion of subjects with KIT mutation

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically or cytologically confirmed diagnosis of 1 of the following:

    • Relapsed or refractory acute myeloid leukemia (AML)
    • Secondary AML including AML arising from antecedent hematologic diseases (e.g., myelodysplastic syndrome, myeloproliferative disorders, or therapy-related AML)
  • Elderly patients ≥ 60 years of age, previously untreated, and who are not candidates for or have refused standard chemotherapy are eligible for this trial
  • Patients with relapsed acute promyelocytic leukemia (APL) who are FLT3+ and have failed both tretinoin and arsenic therapy are eligible for this trial
  • No known active CNS disease
  • ECOG performance status (PS) 0-2 or Karnofsky PS 60-100%
  • Total bilirubin ≤ 2 mg/dL (unless due to disease, hemolysis, or Gilbert disease)

    • In patients with associated hemolysis or Gilbert disease, a bilirubin of > 2 mg/dL is allowed as a result of predominantly unconjugated hyperbilirubinemia
  • AST/ALT < 3 times upper limit of normal
  • Creatinine < 2 mg/dL
  • Baseline pulse oximetry > 92%
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception prior to, during, and for 4 weeks (16 week for males) after completion of study treatment
  • Recovered from prior therapy
  • At least 2 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) or radiotherapy

    • Hydroxyurea may be administered for the first 7 days of therapy in patients with rapidly rising white count (WBC > 20 K/μL)
  • At least 4 weeks since prior investigational agents
  • No prior MEK inhibitors
  • No concurrent medication that can prolong the QT interval
  • No other concurrent investigational agents
  • No concurrent combination antiretroviral therapy for HIV-positive patients

Exclusion Criteria:

  • History of allergic reactions attributed to compounds of similar chemical or biological composition to AZD6244 or its excipient Captisol®
  • QTc interval > 450 msecs or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, or family history of long QT interval syndrome), including New York Heart Association class III or IV heart failure
  • Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g., inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness or social situations that would limit compliance with study requirements

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00588809

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United States, Illinois
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States, 60637-1470
Sponsors and Collaborators
National Cancer Institute (NCI)
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Principal Investigator: Olatoyosi Odenike University of Chicago Comprehensive Cancer Center

Publications of Results:
Other Publications:
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Responsible Party: National Cancer Institute (NCI) Identifier: NCT00588809    
Other Study ID Numbers: NCI-2009-00250
N01CM62209 ( U.S. NIH Grant/Contract )
N01CM62201 ( U.S. NIH Grant/Contract )
First Posted: January 9, 2008    Key Record Dates
Results First Posted: August 5, 2015
Last Update Posted: August 5, 2015
Last Verified: February 2013
Additional relevant MeSH terms:
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Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia, Promyelocytic, Acute
Myelodysplastic Syndromes
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases