An Efficacy and Safety Study of Pevonedistat Plus Azacitidine Versus Single-Agent Azacitidine in Participants With Higher-Risk Myelodysplastic Syndromes (HR MDS), Chronic Myelomonocytic Leukemia (CMML) and Low-Blast Acute Myelogenous Leukemia (AML)
A Phase 2, Randomized, Controlled, Open-Label, Clinical Study of the Efficacy and Safety of Pevonedistat Plus Azacitidine Versus Single-Agent Azacitidine in Patients With Higher-Risk Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia and Low-Blast Acute Myelogenous Leukemia
5 other identifiers
interventional
120
12 countries
59
Brief Summary
The purpose of this study is to evaluate the efficacy and safety of pevonedistat plus azacitidine versus single-agent azacitidine in participants with HR-MDS or CMML, or low-blast AML.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Apr 2016
Longer than P75 for phase_2
59 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
November 18, 2015
CompletedFirst Posted
Study publicly available on registry
November 20, 2015
CompletedStudy Start
First participant enrolled
April 14, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 4, 2019
CompletedResults Posted
Study results publicly available
September 23, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
July 23, 2021
CompletedSeptember 19, 2022
August 1, 2022
3.4 years
November 18, 2015
August 31, 2020
August 24, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Overall Survival (OS)
OS was defined as the time from the date of randomization to the date of death due to any cause. Participants without documented death at the time of the analysis were censored at the date the participant was last known to be alive. The Kaplan Meier estimates was used for the analysis.
From date of randomization until death (up to 3 years and 5 months)
Secondary Outcomes (26)
Event-Free Survival (EFS)
From date of randomization until transformation to AML, or death due to any cause (up to approximately 5 years)
Six-month Survival Rate
Month 6
One-year Survival Rate
Month 12
Time to AML Transformation in HR MDS or CMML Participants
From date of randomization until transformation to AML (up to approximately 5 years)
Percentage of Participants With Complete Remission (CR)
From date of randomization until CR (up to approximately 5 years)
- +21 more secondary outcomes
Study Arms (2)
Azacitidine 75 mg/m^2
ACTIVE COMPARATORAzacitidine 75 mg/m\^2, infusion, intravenously or subcutaneously, on Day 1 through Day 5, Days 8 and 9 in 28-day treatment cycles until unacceptable toxicity, relapse, transformation to AML (for participants with HR MDS or CMML), or progressive disease (for participants with low-blast AML).
Azacitidine 75 mg/m^2 + Pevonedistat 20 mg/m^2
EXPERIMENTALAzacitidine 75 mg/m\^2, infusion, intravenously or subcutaneously, on Day 1 through Day 5, Days 8 and 9 and pevonedistat 20 mg/m\^2, infusion, intravenously, on Days 1, 3, and 5 in 28-day treatment cycles until unacceptable toxicity, relapse, transformation to AML (for participants with HR MDS or CMML), or progressive disease (for participants with low-blast AML).
Interventions
Azacitidine intravenous or subcutaneous formulation.
Eligibility Criteria
You may qualify if:
- Male or female participants 18 years or older.
- Morphologically confirmed diagnosis of MDS or nonproliferative CMML (that is, with white blood cells \[WBC\] \<20,000 per microliter \[/mcL\]) or low blast AML based on 1 of the following:
- French American British (FAB) Classifications:
- Refractory anemia with excess blasts (RAEB) - defined as having 5% to 20% myeloblasts in the bone marrow.
- CMML with 10% to 19% myeloblasts in the bone marrow and/or 5% to 19% blasts in the blood.
- WHO Classifications:
- RAEB 1 - defined as having 5% to 9% myeloblasts in the bone marrow.
- RAEB 2 - defined as having 10% to 19% myeloblasts in the bone marrow and/or 5% to 19% blasts in the blood.
- CMML 2 - defined as having 10% to 19% myeloblasts in the bone marrow and/or 5% to 19% blasts in the blood.
- CMML 1 (Although CMML 1 is defined as having \<10% myeloblasts in the bone marrow and/or \<5% blasts in the blood, these participants may enroll only if bone marrow blasts \>=5%.
- WHO defined AML with 20% to 30% myeloblasts in the bone marrow and \<30% myeloblasts in peripheral blood who are deemed by the investigator to be appropriate for azacitidine based therapy.
- For MDS and CMML participants, prognostic risk category, based on the Revised International Prognostic Scoring System (IPSS R), of:
- Very high (\>6 points),
- High (\>4.5 to 6 points), or
- Intermediate (\>3 to 4.5 points): a participant determined to be in the Intermediate Prognostic Risk Category is only allowable in the setting of \>=5% bone marrow myeloblasts.
- +19 more criteria
You may not qualify if:
- Previous treatment with decitabine or azacitidine or other hypomethylating agent.
- 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.
- Eligible for allogenic stem cell transplantation.
- Participants with MDS, CMML, or low blast AML, whose only site of disease is extramedullary, example, the skin.
- Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of study procedures or could limit participant expected survival to less than 6 months.
- Treatment with any anti leukemic/anti MDS therapies (example, lenalidomide, cytarabine, anthracyclines, purine analogs) or with any investigational products within 14 days before the first dose of any study drug.
- Known hypersensitivity to mannitol.
- Active uncontrolled infection or severe infectious disease, such as severe pneumonia, meningitis, or septicemia.
- Major surgery within 14 days before first dose or a scheduled surgery during study period; insertion of a venous access device (example, catheter, port) is not considered major surgery.
- Diagnosed or treated for another malignancy within 2 years before randomization or previously diagnosed with another malignancy and have any evidence of residual disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone resection.
- Life threatening illness unrelated to cancer.
- Prothrombin time (PT) or prolongation of the activated thromboplastin time (aPTT) \>1.5 ULN or active uncontrolled coagulopathy or bleeding disorder.
- Known human immunodeficiency virus (HIV) seropositive.
- Known hepatitis B surface antigen seropositive, or known or suspected active hepatitis C infection. Note: Participants who have isolated positive hepatitis B core antibody (that is, in the setting of negative hepatitis B surface antigen and negative hepatitis B surface antibody) must have an undetectable hepatitis B viral load.
- Known hepatic cirrhosis or severe pre-existing hepatic impairment.
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (59)
University of Alabama
Birmingham, Alabama, 35233, United States
Greenville Health System
Little Rock, Arkansas, 72201, United States
UC San Diego Moores Cancer Center
La Jolla, California, 92093, United States
Compassionate Cancer Care Medical Group Incorporated
Riverside, California, 92501, United States
Rocky Mountain Cancer Centers
Aurora, Colorado, 80012, United States
Smilow Cancer Center at Yale New Haven Hospital
New Haven, Connecticut, 06510, United States
University of Miami Miller School of Medicine
Miami, Florida, 33136, United States
H Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612, United States
University of Chicago Medical Center
Chicago, Illinois, 60637, United States
Johns Hopkins University
Baltimore, Maryland, 21287, United States
San Juan Oncology Associates
Farmington, New Mexico, 87401, United States
Monter Cancer Center
Lake Success, New York, 11042, United States
Weill Cornell Medical College
New York, New York, 10021, United States
Columbia University Medical Center
New York, New York, 10032, United States
University of Rochester Medical Center
Rochester, New York, 14603, United States
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599, United States
Cleveland Clinic
Cleveland, Ohio, 44195, United States
Cancer Care Center of South Texas
New Braunfels, Texas, 78130, United States
Nebraska Cancer Specialists
The Woodlands, Texas, 77380, United States
Texas Oncology - Waco, TX
Tyler, Texas, 76712, United States
University of Virginia
Charlottesville, Virginia, 22903, United States
Medical Oncology Associates
Spokane, Washington, 99208, United States
Yakima Valley Memorial Hospital
Yakima, Washington, 98902, United States
AZ Sint-Jan AV
Bruges, West-Vlaanderen, 8400, Belgium
Grand Hopital de Charleroi asbl
Charleroi, 6000, Belgium
Cliniques Universitaires UCL de Mont-Godinne
Yvoir, 5500, Belgium
University Multiprofile Hospital for Active Treatment Sv Ivan Rilski EAD
Sofia, 1113, Bulgaria
Specialized Hospital for Active Treatment of Haematological Diseases - Sofia
Sofia, 1756, Bulgaria
University Multi-Profile Hospital for Active Treatment Dr Georgi Stranski
Sofia, 1756, Bulgaria
Sunnybrook Health Science Centre
Toronto, Ontario, M4N 3M5, Canada
Princess Margaret Hospital
Toronto, Ontario, M5G 2M9, Canada
Fakultni Nemocnice Brno
Brno, 625 00, Czechia
Fakultni Nemocnice Kralovske Vinohrady
Prague, 10034, Czechia
CHU de GRENOBLE
Grenoble, 38700, France
CHRU Lille
Lille, 59000, France
Hopital Saint Louis
Paris, 75010, France
Marien Hospital Akademisches Lehrkrankenhaus
Düsseldorf, 40479, Germany
Universitatsklinikum Ulm
Ulm, 89081, Germany
Tallaght Hospital
Dublin, 24, Ireland
University Hospital Galway
Galway, Ireland
Shaare Zedek Medical Center
Jerusalem, 9103102, Israel
ZIV Medical Center
Safed, 13100, Israel
Tel Aviv Sourasky Medical Center
Tel Aviv, 13100, Israel
Azienda Ospedaliero Universitaria Di Bologna - Policlinico S Orsola Malpighi
Bologna, 40138, Italy
Azienda Ospedaliera Universitaria Careggi
Florence, 50139, Italy
Azienda Ospedaliera Bianchi Melacrino Morelli
Reggio Calabria, 89100, Italy
Azienda Ospedaliero Universitaria San Giovanni Battista Di Torino
Torino, 10126, Italy
Zuyderland Medisch Centrum
Sittard, 6162 BG, Netherlands
Hospital Universitario Son Espases
Palma de Mallorca, Balearic Islands, 7010, Spain
Hospital Universitario Quironsalud Madrid
Pozuelo de Alarcón, Madrid, 28223, Spain
Hospital Universitario Germans Trias i Pujol
Badalona, 8916, Spain
ICO I'Hospitalet Hospital Duran i Reynals Instituto Catalan de Oncologia de Hospitalet (ICO)
Barcelona, 08908, Spain
Hospital Clinic de Barcelona
Barcelona, 8036, Spain
Hospital General Universitario Gregorio Maranon
Madrid, 28007, Spain
Hospital Universitario La Paz
Madrid, 28046, Spain
Hospital Regional Universitario de Malaga - Hospital Universitario Virgen de la Victoria
Málaga, 29010, Spain
Hospital Universitario de Salamanca
Salamanca, 37007, Spain
Hospital Clinico Universitario de Valencia
Valencia, 46010, Spain
Hospital Universitari i Politecnic La Fe de Valencia
Valencia, 46026, Spain
Related Publications (1)
Sekeres MA, Watts J, Radinoff A, Sangerman MA, Cerrano M, Lopez PF, Zeidner JF, Campelo MD, Graux C, Liesveld J, Selleslag D, Tzvetkov N, Fram RJ, Zhao D, Bell J, Friedlander S, Faller DV, Ades L. Randomized phase 2 trial of pevonedistat plus azacitidine versus azacitidine for higher-risk MDS/CMML or low-blast AML. Leukemia. 2021 Jul;35(7):2119-2124. doi: 10.1038/s41375-021-01125-4. Epub 2021 Jan 22. No abstract available.
PMID: 33483617DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Takeda
Study Officials
- STUDY DIRECTOR
Medical Director
Millennium Pharmaceuticals, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 18, 2015
First Posted
November 20, 2015
Study Start
April 14, 2016
Primary Completion
September 4, 2019
Study Completion
July 23, 2021
Last Updated
September 19, 2022
Results First Posted
September 23, 2020
Record last verified: 2022-08
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR
- Access Criteria
- IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.