Study of MLN4924 Plus Azacitidine in Treatment-naive Participants With Acute Myelogenous Leukemia (AML) Who Are 60 Years or Older
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
2 other identifiers
interventional
64
1 country
8
Brief Summary
The purpose of this study is to establish the maximum tolerated dose (MTD), and to assess the safety and tolerability of MLN4924 (pevonedistat) in combination with azacitidine in treatment naive participants with AML who were 60 years of age or older.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Apr 2013
Longer than P75 for phase_1
8 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 18, 2013
CompletedFirst Posted
Study publicly available on registry
March 20, 2013
CompletedStudy Start
First participant enrolled
April 10, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 3, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
April 8, 2018
CompletedResults Posted
Study results publicly available
March 3, 2020
CompletedMarch 3, 2020
February 1, 2020
3.1 years
March 18, 2013
December 5, 2019
February 18, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Baseline up to 30 days after the last dose of study drug (up to 5 years)
Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings
Baseline up to 30 days after the last dose of study drug (up to 5 years)
Number of Participants With TEAEs Related to Clinically Significant Vital Sign Findings
Baseline up to 30 days after the last dose of study drug (up to 5 years)
Secondary Outcomes (27)
Dose-escalation Phase, Cmax: Maximum Observed Plasma Concentration for MLN4924
Cycle 1 Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose; Cycle 1 Day 5 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle length is equal to [=] 28 days)
Maximum Tolerated Dose (MTD) Expansion Phase, Cmax: Maximum Observed Plasma Concentration for MLN4924
Cycle 1 Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose; Cycle 1 Day 5 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle length = 28 days)
Dose-escalation Phase, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MLN4924
Cycle 1 Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose; Cycle 1 Day 5 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle length = 28 days)
MTD Expansion Phase, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MLN4924
Cycle 1 Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose; Cycle 1 Day 5 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle length = 28 days)
Dose-escalation Phase, Ctrough: Observed Plasma Concentration at the End of the Dosing Interval for MLN4924
Cycle 1 Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose; Cycle 1 Day 5 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle length = 28 days)
- +22 more secondary outcomes
Study Arms (1)
MLN4924 and Azacitidine
EXPERIMENTALInterventions
MLN4924 intravenously (IV) in AML participants in a 28-day cycle: * MLN4924 on Days 1, 3, and 5 for Cycle 1 and all subsequent cycles
Azacitidine (IV) or subcutaneously in AML participants in a 28-day cycle: \- Azacitidine Days 1, 2, 3, 4, 5, 8, 9 in Cycle 1 and for all subsequent cycles
Eligibility Criteria
You may qualify if:
- Participants with world health organization (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:
- Greater than or equal to 75 years of age.
- Antecedent hematologic disease.
- Known adverse cytogenetic risk.
- Eastern Cooperative Oncology Group (ECOG) PS = 2.
- Participant 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 participants who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or agree to practice true abstinence.
- Male participants 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.
- Clinical laboratory values as specified below within 3 days before the first dose of any study drug:
- Total bilirubin must be less than or equal to (\<=) the upper limit of the normal range (ULN).
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must be\<=2.5\*ULN.
- +6 more criteria
You may not qualify if:
- 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.
- WBC count greater than (\>) 50,000/ mcL.
- Prothrombin time (PT) or activated partial thromboplastin time (aPTT) \>1.5\* ULN or a history of coagulopathy or bleeding disorder
- 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.
- +14 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (8)
University of Alabama at Birmingham
Birmingham, Alabama, 35294, United States
Stanford University
Stanford, California, 94305-5826, United States
Hospital Corporation of America-HealthOne, LLC
Denver, Colorado, 80218, United States
Mayo Clinic - Jacksonville, FL
Jacksonville, Florida, 32224, United States
University of Miami School of Medicine
Miami, Florida, 33136, United States
UNC-Chapel Hill School of Medicine
Chapel Hill, North Carolina, 27599, United States
Sarah Cannon Research Institute
Nashville, Tennessee, 37203, United States
Methodist Hospital
San Antonio, Texas, 78229, United States
Related Publications (2)
Swords RT, Coutre S, Maris MB, Zeidner JF, Foran JM, Cruz J, Erba HP, Berdeja JG, Tam W, Vardhanabhuti S, Pawlikowska-Dobler I, Faessel HM, Dash AB, Sedarati F, Dezube BJ, Faller DV, Savona MR. Pevonedistat, a first-in-class NEDD8-activating enzyme inhibitor, combined with azacitidine in patients with AML. Blood. 2018 Mar 29;131(13):1415-1424. doi: 10.1182/blood-2017-09-805895. Epub 2018 Jan 18.
PMID: 29348128RESULTFaessel HM, Mould DR, Zhou X, Faller DV, Sedarati F, Venkatakrishnan K. Population pharmacokinetics of pevonedistat alone or in combination with standard of care in patients with solid tumours or haematological malignancies. Br J Clin Pharmacol. 2019 Nov;85(11):2568-2579. doi: 10.1111/bcp.14078. Epub 2019 Sep 4.
PMID: 31355467DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical director
- Organization
- Takeda
Study Officials
- STUDY DIRECTOR
Medical Monitor
Millennium Pharmaceuticals, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Masking
- NONE
- Purpose
- OTHER
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 18, 2013
First Posted
March 20, 2013
Study Start
April 10, 2013
Primary Completion
May 3, 2016
Study Completion
April 8, 2018
Last Updated
March 3, 2020
Results First Posted
March 3, 2020
Record last verified: 2020-02
Data Sharing
- IPD Sharing
- Will share
Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.