Selumetinib in Treating Patients With Recurrent or Refractory Acute Myeloid Leukemia

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00588809
First received: December 21, 2007
Last updated: April 10, 2013
Last verified: February 2013
  Purpose

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 Intervention 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
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of AZD6244 in Relapsed or Refractory AML

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Response rate (CR, CR with incomplete count recovery, partial response, and minor response) to AZD6244 [ Time Frame: Up to 52 weeks ] [ Designated as safety issue: No ]
    A Simon, optimal two-stage design will be employed in cohort A. For Cohort B, we will determine the response rate and provide an exact 90% confidence interval using the binomial distribution. The response rate in these patients will be compared to that observed in the main cohort using Fisherâs exact test.


Secondary Outcome Measures:
  • Response rates in patients with and without a mutation in RAS genes [ Time Frame: Up to 52 weeks ] [ Designated as safety issue: No ]
    Fisher's exact test will be utilized to compare response rates in those with and without a mutation in RAS genes.

  • Changes in p-ERK [ Time Frame: From baseline to 1 month ] [ Designated as safety issue: No ]
    Wilcoxon nonparametric rank test will be utilized to assess changes in p-ERK from baseline to 1 week and baseline to 1 month.


Estimated Enrollment: 45
Study Start Date: December 2007
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

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).

SECONDARY OBJECTIVES:

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.

OUTLINE:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00588809

Locations
United States, Illinois
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States, 60637-1470
Sponsors and Collaborators
Investigators
Principal Investigator: Olatoyosi Odenike University of Chicago Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00588809     History of Changes
Other Study ID Numbers: NCI-2009-00250, 15455B, N01CM62209, N01CM62201
Study First Received: December 21, 2007
Last Updated: April 10, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia, Promyelocytic, Acute
Myelodysplastic Syndromes
Preleukemia
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions

ClinicalTrials.gov processed this record on July 23, 2014