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Study of MLN4924 Plus Azacitidine in Treatment-Naïve Patients With Acute Myelogenous Leukemia (AML) Who Are 60 Years or Older

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: NCT01814826
Recruitment Status : Completed
First Posted : March 20, 2013
Last Update Posted : August 17, 2018
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Brief Summary:
This study is an open-label, multicenter, phase 1b, dose-escalation study of MLN4924 in combination with azacitidine in adult patients with AML. The patient population will consist of patients 60 years of age or older, previously diagnosed with World Health Organization(WHO)-defined AML, who are unlikely to benefit from standard induction therapy and who have not received definitive treatment for AML or prior treatment with azacitidine or decitabine.

Condition or disease Intervention/treatment Phase
Acute Myelogenous Leukemia Drug: MLN4924 and azacitidine Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 64 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b, Open-Label, Dose-Escalation Study of MLN4924 Plus Azacitidine in Treatment-Naïve Patients With Acute Myelogenous Leukemia Who Are 60 Years or Older
Actual Study Start Date : April 15, 2013
Actual Primary Completion Date : May 3, 2016
Actual Study Completion Date : April 8, 2018

Arm Intervention/treatment
Experimental: MLN4924 and azacitidine Drug: MLN4924 and azacitidine

MLN4924 (IV) and azacitidine (IV) in AML patients to determine maximum tolerated dose (MTD) on a 28-day cycle:

  • Azacitidine Days 1, 2, 3, 4, 5, 8, 9 in Cycle 1 and for all subsequent cycles
  • MLN4924 on Days 1, 3, and 5 for Cycle 1 and all subsequent cycles
  • Both agents given on Days 1, 3, and 5 of Cycle 1 and all subsequent cycles

Primary Outcome Measures :
  1. Number of Adverse events [ Time Frame: Recorded from the first dose of any study drug through 30 days (+ 10 days) after the last dose of study drug ]
    To assess the safety and tolerability of MLN4924 in combination with azacitidine.

Secondary Outcome Measures :
  1. Pharmacokinetic parameters including but not limited to AUC, Cmax, Systemic Clearance, Volume of Distribution, Elimination of Half-Life [ Time Frame: Days 1 and 5 of Cycle 1 ]
  2. Disease response rate [ Time Frame: Cycle 1 Day 22 and assessment of treatment-emergent resistance at Cycle 2 & Cycle 4 any time between Day 20 & Day 28. After Cycle 4, bone marrow assessments will be performed after completion of every third cycle (ie, Cycle 7, Cycle 10, etc.). ]
  3. Thirty-day mortality rate [ Time Frame: 30 days after the first dose of study drug on Cycle 1 ]
  4. 60 Day Mortality Rate [ Time Frame: 60 days after the first dose of study drug on Cycle 1 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   60 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients with WHO-defined AML, 60 years of age or older, who are unlikely to benefit from standard induction therapy, defined as having at least 1 of the following:

    1. Greater than or equal to 75 years of age
    2. Antecedent hematologic disease
    3. Known adverse cytogenetic risk
    4. Eastern Cooperative Oncology Group (ECOG) PS = 2
  • Patient must not have received definitive treatment for AML, defined as any prior chemotherapy with antileukemic activity
  • ECOG PS 0 to 2
  • Expected survival longer than 3 months from enrollment in the study
  • Female patients who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or agree to practice true abstinence
  • Male patients who agree to practice effective barrier contraception or agree to practice true abstinence
  • Voluntary written consent must be given before performance of any study-related procedure
  • Suitable venous access for the study-required blood sampling
  • Adequate clinical laboratory values during the screening period as specified in the protocol
  • Able to undergo bone marrow aspiration and biopsy at screening

Exclusion Criteria:

  • Previous treatment with azacitidine or decitabine
  • Known favorable cytogenetic risk
  • Any serious medical or psychiatric illness
  • Treatment with any investigational products
  • Known hypersensitivity to azacitidine or mannitol
  • Acute promyelocytic leukemia as diagnosed by morphologic examination of bone marrow, by fluorescent in situ hybridization or cytogenetics of peripheral blood or bone marrow, or by other accepted analysis
  • Active uncontrolled infection or severe infectious disease
  • Major surgery within 14 days before the first dose of study drug
  • Life-threatening illness unrelated to cancer
  • Clinically uncontrolled central nervous system (CNS) involvement
  • Known human immunodeficiency virus (HIV) positive
  • Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection
  • Known hepatic cirrhosis or severe pre-existing hepatic impairment
  • Known cardiac/cardiopulmonary disease
  • Left ventricular ejection fraction
  • Known moderate to severe chronic obstructive pulmonary disease, interstitial lung disease, and pulmonary fibrosis
  • Body mass index > 40 kg/m²
  • Treatment with CYP3A inducers within 14 days before the first dose of MLN4924
  • Systemic antineoplastic therapy or radiotherapy within 14 days before the first dose of study drug, except for hydroxyurea
  • Patients who are unwilling or unable to refrain from using hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitors (statins) starting 5 days before the initial study drug administration and throughout the study will not be permitted to enroll

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): NCT01814826

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United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, California
Stanford University
Stanford, California, United States, 94305-5826
United States, Colorado
Hospital Corporation of America-HealthOne, LLC
Denver, Colorado, United States, 80218
United States, Florida
Mayo Clinic - Jacksonville, FL
Jacksonville, Florida, United States, 32224
University of Miami School of Medicine
Miami, Florida, United States, 33136
United States, North Carolina
UNC-Chapel Hill School of Medicine
Chapel Hill, North Carolina, United States, 27599
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
United States, Texas
Methodist Hospital
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
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Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Millennium Pharmaceuticals, Inc. Identifier: NCT01814826     History of Changes
Other Study ID Numbers: C15009
First Posted: March 20, 2013    Key Record Dates
Last Update Posted: August 17, 2018
Last Verified: August 2018
Keywords provided by Takeda ( Millennium Pharmaceuticals, Inc. ):
Additional relevant MeSH terms:
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Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors