Clinical trial NCT03268954: Pevonedistat Plus Azacitidine Versus Single-Agent Azacitidine as First-Line Treatment for Participants With Higher-Risk Myelodysplastic Syndromes (HR MDS), Chronic Myelomonocytic Leukemia (CMML), or Low-Blast Acute Myelogenous Leukemia (AML)
Official title: A Phase 3, Randomized, Controlled, Open-label, Clinical Study of Pevonedistat Plus Azacitidine Versus Single-Agent Azacitidine as First-Line Treatment for Patients With Higher-Risk Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Low-Blast Acute Myelogenous Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Myelodysplastic Syndrome
Leukemia, Myelomonocytic, Chronic
Leukemia, Myeloid, Acute
Keywords: Drug therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Takeda Development Center Americas, Inc.
First posted: 2017-08-31
Enrollment: 454
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether the combination of pevonedistat and azacitidine improves event-free survival (EFS) when compared with single-agent azacitidine. (An event is defined as death or transformation to AML in participants with MDS or CMML, whichever occurs first, and is defined as death in participants with low-blast AML).

Detailed description: The drug being tested in this study is called pevonedistat. Pevonedistat is being tested to treat people with higher-risk myelodysplastic syndromes (HR MDS), chronic myelomonocytic leukemia (CMML) and low-blast acute myelogenous leukemia (AML) as a combination treatment with azacitidine. This study will look at the overall survival, event-free survival and response to treatment in people who take pevonedistat and azacitidine when compared to people who take single-agent azacitidine.

The study will enroll approximately 450 participants. Once enrolled, participants will be randomly assigned in 1:1 ratio (by chance, like flipping a coin) to one of the two treatment groups in 28-day treatment cycles:

* Pevonedistat 20 mg/m\^2 and azacitidine 75 mg/m\^2 combination
* Single-agent azacitidine 75 mg/m\^2

All participants will receive azacitidine via intravenous or subcutaneous route. Participants randomized to the combination arm will also receive pevonedistat intravenous infusion.

This multi-center trial will be conducted Spain, Belgium, Brazil, Canada, Czech Republic, France, Germany, Israel, Italy, the United States, Australia, Greece, Japan, Mexico, Poland, Russia, Korea, Turkey, China and United Kingdom. The overall time to participate in this study is approximately 63 months. Participants will attend the end-of-treatment visit 30 days after the last dose of study drug or before the start of subsequent anti-neoplastic therapy if that occurs sooner.

Participants with HR MDS or CMML will have EFS follow-up study visits every month if their disease has not transformed to AML and they have not started subsequent therapy. Participants with low-blast AML will have response follow-up study visits every month until they relapse from CR or meet the criteria for PD. All participants will enter OS follow-up (contacted every 3 months) when they have confirmed transformation to AML (for participants with HR MDS or CMML at enrollment) or experienced PD (for participants with low-blast AML at study enrollment).

Eligibility criteria: Inclusion Criteria:

1. Has morphologically confirmed diagnosis of myelodysplastic syndromes (MDS) or CMML (i.e., with white blood cell \[WBC\] \<13,000/microliter \[mcL\]) or low-blast acute myelogenous leukemia (AML).
2. Has MDS or CMML and must also have one of the following Prognostic Risk Categories, based on the Revised International Prognostic Scoring System (IPSS-R):

   * Very high (\>6 points).
   * High (\>4.5-6 points).
   * Intermediate (\>3-4.5 points): a participant determined to be in the Intermediate Prognostic Risk Category is only allowable in the setting of \>=5% bone marrow myeloblasts.
3. Eastern Cooperative Oncology Group (ECOG) status of 0, 1, or 2.
4. Participants with AML (20%-30% blasts) must have a treatment-related mortality (TRM) score \>=4 for intensive, induction chemotherapy as calculated using the simplified model described by Walter and coworkers.

Calculation of TRM score:

* 0 for (age \<61 years), +2 for (age 61-70 years), +4 for (age \>=71 years).
* + 0 for (PS=0), +2 for (PS=1), +4 for (PS \>1).
* + 0 for (platelets \<50), +1 for (platelets \>=50).

Exclusion Criteria:

1. Has previous treatment for HR MDS or CMML or low-blast AML with chemotherapy or other antineoplastic agents including hypomethylating agent (HMAs) such as decitabine or azacitidine. Previous treatment is permitted with hydroxyurea and with lenalidomide, except that lenalidomide may not be given within 8 weeks before the first dose of study drug.
2. Has 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.
3. Participants with AML with a WBC count \>50,000/mcL. Participants who are cytoreduced with leukapheresis or with hydroxyurea may be enrolled if they meet the eligibility criteria.
4. Is eligible for intensive chemotherapy and/or allogeneic stem cell transplantation. The reason a participant is not eligible for intensive chemotherapy and/or allogeneic stem cell transplantation may consist of one or more of the following factors:

   * Age \>75.
   * Comorbidities.
   * Inability to tolerate intensive chemotherapy (e.g., participants with AML with 20%-30% blasts and TRM \>=4).
   * Physician decision (e.g., lack of available stem cell donor).
   * The reason a participant is not eligible should be documented in the electronic case report form (eCRF).
5. Has either clinical evidence of or history of central nervous system involvement by AML.
6. Has active uncontrolled infection or severe infectious disease, such as severe pneumonia, meningitis, or septicemia.
7. Is diagnosed or treated for another malignancy within 2 years before randomization or previously diagnosed with another malignancy and have any evidence of residual disease.
8. Has nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone resection.
9. Has prothrombin time (PT) or aPTT \>1.5× upper limit of normal (ULN) or active uncontrolled coagulopathy or bleeding disorder. Participants therapeutically anticoagulated with warfarin, direct thrombin inhibitors, direct factor Xa inhibitors, or heparin are excluded from enrollment.
10. Has known human immunodeficiency virus (HIV) seropositive.
11. Has known hepatitis B surface antigen seropositive, or known or suspected active hepatitis C infection. Note: Participants who have isolated positive hepatitis B core antibody (i.e., in the setting of negative hepatitis B surface antigen and negative hepatitis B surface antibody) must have an undetectable hepatitis B viral load.
12. Has known hepatic cirrhosis or severe preexisting hepatic impairment.
13. Has known cardiopulmonary disease defined as unstable angina, clinically significant arrhythmia, congestive heart failure (New York Heart Association Class III or IV), and/or myocardial infarction within 6 months before first dose, or severe pulmonary hypertension.
14. Has treatment with strong cytochrome P 3A (CYP3A) inducers within 14 days before the first dose of pevonedistat.

Primary outcomes:
measure: Event-Free Survival (EFS)
timeFrame: From randomization until transformation to acute myeloid leukemia, or death due to any cause up to data cut-off date: 28 May 2021 (up to approximately 42 months)
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to data cut-off date: 28 May 2021 (up to approximately 42 months)
measure: Kaplan-Meier Estimates of Six-Month Survival Rate
timeFrame: Up to Month 6
measure: Kaplan-Meier Estimates of One-Year Survival Rate
timeFrame: Up to Year 1
measure: Thirty-Day Mortality Reported as Number of Participants Who Died Up to Day 30
timeFrame: Up to Day 30
measure: Sixty-Day Mortality Reported as Number of Participants Who Died Up to Day 60
timeFrame: Up to Day 60
measure: Time to Acute Myelogenous Leukemia (AML) Transformation in Higher-Risk Myelodysplastic Syndromes (HR MDS), Higher-Risk Chronic Myelomonocytic Leukemias (HR CMML) and HR MDS/CMML Participants
timeFrame: From randomization until transformation to AML till data cut-off date: 28 May 2021 (up to approximately 42 months)
measure: Number of Participants With Complete Remission (CR) and CR+ Complete Remission With Incomplete Blood Count Recovery (CRi)
timeFrame: From randomization until CR till data cut-off date: 28 May 2021 (up to approximately 42 months)
measure: Number of Participants With CR and Marrow CR
timeFrame: From randomization until CR or marrow CR till data cut-off date: 28 May 2021 (up to approximately 42 months)
measure: Number of Participants With CR, Partial Remission (PR) and Hematologic Improvement (HI)
timeFrame: From randomization until, CR, PR or HI till data cut-off date: 28 May 2021 (up to approximately 42 months)
measure: Number of Participants With CR and Marrow CR and PR
timeFrame: From randomization until CR or Marrow CR and PR till data cut-off date: 28 May 2021 (up to approximately 42 months)
measure: Number of Participants With CR and Marrow CR, PR and Hematologic Improvement (HI)
timeFrame: From randomization until CR, marrow CR, PR or HI till data cut-off date: 28 May 2021 (up to approximately 42 months)
measure: Number of Participants With Overall Response (OR)
timeFrame: From randomization until CR and PR or CR, CRi and PR till data cut-off date: 28 May 2021 (up to approximately 42 months)
measure: Number of Participants With Overall Response 2 (OR2)
timeFrame: From randomization until, CR, PR or HI or CR, CRi or PR till data cut-off date: 28 May 2021 (up to approximately 42 months)
measure: Duration of Complete Remission (CR)
timeFrame: From CR until first documentation of PD or relapse from CR or relapse after CR or PR till data cut-off date: 28 May 2021 (up to approximately 42 months)
measure: Duration of Complete Remission + Complete Remission With Incomplete Blood Count Recovery (CRi)
timeFrame: From CR until first documentation of PD or relapse from CR or relapse after CR or PR till data cut-off date: 28 May 2021 (up to approximately 42 months)
measure: Duration of Overall Response (OR)
timeFrame: Up to data cut-off date: 28 May 2021 (up to approximately 42 months)
measure: Duration of Overall Response 2 (OR2)
timeFrame: Up to data cut-off date: 28 May 2021 (up to approximately 42 months)
measure: Percentage of Participants With Red Blood Cells (RBCs) and Platelet-transfusion Independence
timeFrame: Up to data cut-off date: 28 May 2021 (up to approximately 42 months)
measure: Duration of Red Blood Cells (RBCs) and Duration of Platelet-transfusion Independence and Duration of Red Blood Cells (RBCs) and Platelet-transfusion Independence
timeFrame: Up to data cut-off date: 28 May 2021 (up to approximately 42 months)
measure: Time to First Complete Remission (CR) or Partial Remission (PR) or Complete Remission With Incomplete Blood Count Recovery (CRi)
timeFrame: From randomization until CR or PR till data cut-off date: 28 May 2021 (up to approximately 42 months)
measure: Number of Participants With Hematologic Improvement (HI)
timeFrame: From randomization until HI till data cut-off date: 28 May 2021 (up to approximately 42 months)
measure: Number of Participants With at Least 1 Inpatient Hospital Admissions Related to HR MDS, CMML or Low-blast AML
timeFrame: From randomization until transformation to AML or until initiation of subsequent therapy till data cut-off date: 28 May 2021 (up to approximately 42 months)
measure: Time to Progressive Disease (PD), Relapse After CR (Low-blast AML), Relapse After CR or PR (HR MDS/CMML), or Death
timeFrame: From randomization until PD, relapse after CR, or relapse after CR or PR, or death due to any cause, whichever occurs first till data cut-off date: 28 May 2021 (up to approximately 42 months)
measure: Health-Related Quality of Life (HRQOL) Using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire- Core 30
timeFrame: Up to data cut-off date: 28 May 2021 (up to approximately 42 months)
measure: Plasma Concentration of Pevonedistat
timeFrame: Cycle 1 Day 1 predose and multiple time points (up to 4 hours) post dose; Cycle 1 Days 3 and 5 predose; Cycle 2 and 4 Day 1 at multiple time points (up to 3 hours) post dose; Cycle 4 Day 3 predose (Cycle length= 28 days)
measure: Number of Participants With Overall Response in Participants Who Have TP53 Mutations, 17p Deletions, and/or Are Determined to be in an Adverse Cytogenetic Risk Group
timeFrame: From randomization until CR, CRi and PR till data cut-off date: 28 May 2021 (up to approximately 42 months)
measure: Event-Free Survival in Participants Who Have TP53 Mutations, 17p Deletions, and/or Are Determined to be in an Adverse Cytogenetic Risk Group
timeFrame: From randomization until transformation to AML if eligible or death till data cut-off date: 28 May 2021 (up to approximately 42 months)
measure: Overall Survival in Participants Who Have TP53 Mutations, 17p Deletions, and/or Are Determined to be in an Adverse Cytogenetic Risk Group
timeFrame: From randomization until death till data cut-off date: 28 May 2021 (up to approximately 42 months)
measure: Number of Participants With Overall Response by Cycle 6
timeFrame: Up to Cycle 6 (up to approximately Day 168)
Other outcomes:
Locations:
city: Daphne
country: United States
facility: Southern Cancer Center - USOR
state: Alabama
city: Mobile
country: United States
facility: Southern Cancer Center - USOR
state: Alabama
city: Mobile
country: United States
facility: Southern Cancer Center - USOR
state: Alabama
city: Mobile
country: United States
facility: Southern Cancer Center- USOR
state: Alabama
city: Goodyear
country: United States
facility: Southeastern Regional Medical Center - CTCA - PPDS
state: Arizona
city: Tucson
country: United States
facility: Arizona Oncology Associates (Orange HOPE) - USOR
state: Arizona
city: Tucson
country: United States
facility: Arizona Oncology Associates (Rudasill HOPE) - USOR
state: Arizona
city: Tucson
country: United States
facility: Arizona Oncology Associates (Wilmot HOPE) - USOR
state: Arizona
city: Corona
country: United States
facility: Compassionate Care Research Group Inc. at Compassionate Cancer Care Medical Group, Inc
state: California
city: Fountain Valley
country: United States
facility: Compassionate Cancer Care Medical Group Inc
state: California
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Redlands
country: United States
facility: Emad Ibrahim, MD, Inc
state: California
city: Riverside
country: United States
facility: Compassionate Care Research Group Inc. at Compassionate Cancer Care Medical Group, Inc
state: California
city: Aurora
country: United States
facility: Rocky Mountain Cancer Centers (Aurora) - USOR
state: Colorado
city: Boulder
country: United States
facility: Rocky Mountain Cancer Centers (Boulder) - USOR
state: Colorado
city: Colorado Springs
country: United States
facility: Rocky Mountain Cancer Centers (Colorado Springs) - USOR
state: Colorado
city: Denver
country: United States
facility: Quest Diagnostics, INC
state: Colorado
city: Denver
country: United States
facility: Colorado Blood Cancer Institute - PPDS
state: Colorado
city: Denver
country: United States
facility: Presbyterian Saint Lukes Medical Center Laboratory
state: Colorado
city: Denver
country: United States
facility: Presbyterian/St. Luke's Medical Center
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers (Williams) - USOR
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers (Denver) - USOR
state: Colorado
city: Denver
country: United States
facility: Kaiser Foundation Health Plan
state: Colorado
city: Englewood
country: United States
facility: Laboratory Corporation of America
state: Colorado
city: Lakewood
country: United States
facility: Rocky Mountain Cancer Centers (Lakewood) - USOR
state: Colorado
city: Littleton
country: United States
facility: Rocky Mountain Cancer Centers (Littleton) - USOR
state: Colorado
city: Lone Tree
country: United States
facility: Rocky Mountain Cancer Centers (Lone Tree) - USOR
state: Colorado
city: Longmont
country: United States
facility: Rocky Mountain Cancer Centers (Longmont) - USOR
state: Colorado
city: Parker
country: United States
facility: Rocky Mountain Cancer Centers (Parker) - USOR
state: Colorado
city: Pueblo
country: United States
facility: Rocky Mountain Cancer Centers (Pueblo) - USOR
state: Colorado
city: Thornton
country: United States
facility: Rocky Mountain Cancer Centers (Thornton) - USOR
state: Colorado
city: Washington
country: United States
facility: Medstar Research Institute
state: District of Columbia
city: Altamonte Springs
country: United States
facility: Florida Cancer Specialists - NORTH - SCRI - PPDS
state: Florida
city: Bonita Springs
country: United States
facility: SCRI Florida Cancer Specialists South
state: Florida
city: Bradenton
country: United States
facility: SCRI Florida Cancer Specialists South
state: Florida
city: Brandon
country: United States
facility: Florida Cancer Specialists - NORTH - SCRI - PPDS
state: Florida
city: Cape Coral
country: United States
facility: SCRI Florida Cancer Specialists South
state: Florida
city: Clearwater
country: United States
facility: Florida Cancer Specialists - NORTH - SCRI - PPDS
state: Florida
city: Fort Myers
country: United States
facility: SCRI Florida Cancer Specialists South
state: Florida
city: Fort Myers
country: United States
facility: SCRI Florida Cancer Specialists South
state: Florida
city: Fort Myers
country: United States
facility: SCRI Florida Cancer Specialists South
state: Florida
city: Gainesville
country: United States
facility: Florida Cancer Specialists - NORTH - SCRI - PPDS
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville - PPDS
state: Florida
city: Largo
country: United States
facility: Florida Cancer Specialists - NORTH - SCRI - PPDS
state: Florida
city: Lecanto
country: United States
facility: Florida Cancer Specialists - NORTH - SCRI - PPDS
state: Florida
city: Miami
country: United States
facility: University of Miami Miller School of Medicine
state: Florida
city: Miami
country: United States
facility: Baptist Health System (N Kendall) - USOR
state: Florida
city: Naples
country: United States
facility: SCRI Florida Cancer Specialists South
state: Florida
city: New Port Richey
country: United States
facility: Florida Cancer Specialists - NORTH - SCRI - PPDS
state: Florida
city: Ocala
country: United States
facility: Florida Cancer Specialists - NORTH - SCRI - PPDS
state: Florida
city: Orange City
country: United States
facility: Florida Cancer Specialists - NORTH - SCRI - PPDS
state: Florida
city: Orlando
country: United States
facility: Florida Cancer Specialists - NORTH - SCRI - PPDS
state: Florida
city: Port Charlotte
country: United States
facility: SCRI Florida Cancer Specialists South
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists - NORTH - SCRI - PPDS
state: Florida
city: Sarasota
country: United States
facility: SCRI Florida Cancer Specialists South
state: Florida
city: Sarasota
country: United States
facility: SCRI Florida Cancer Specialists South
state: Florida
city: Spring Hill
country: United States
facility: Florida Cancer Specialists - NORTH - SCRI - PPDS
state: Florida
city: Tampa
country: United States
facility: Florida Cancer Specialists - NORTH - SCRI - PPDS
state: Florida
city: Tavares
country: United States
facility: Florida Cancer Specialists - NORTH - SCRI - PPDS
state: Florida
city: The Villages
country: United States
facility: Florida Cancer Specialists - NORTH - SCRI - PPDS
state: Florida
city: Venice
country: United States
facility: SCRI Florida Cancer Specialists South
state: Florida
city: Venice
country: United States
facility: SCRI Florida Cancer Specialists South
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Winter Park
country: United States
facility: Florida Cancer Specialists - NORTH - SCRI - PPDS
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute, Emory University
state: Georgia
city: Boise
country: United States
facility: Saint Alphonsus Regional Medical Center
state: Idaho
city: Caldwell
country: United States
facility: Saint Alphonsus Caldwell Cancer Care Center
state: Idaho
city: Nampa
country: United States
facility: Saint Alphonsus Medical Center
state: Idaho
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Overland Park
country: United States
facility: Menorah Medical Center
state: Kansas
city: Independence
country: United States
facility: Centerpoint Medical Center
state: Missouri
city: Kansas City
country: United States
facility: HCA Midwest Health - SCRI - PPDS
state: Missouri
city: Kansas City
country: United States
facility: Research Medical Center
state: Missouri
city: Omaha
country: United States
facility: Nebraska Cancer Specialists
state: Nebraska
city: Brick
country: United States
facility: New Jersey Hematology Oncology Associates LLC
state: New Jersey
city: Hackensack
country: United States
facility: John Theurer Cancer Center
state: New Jersey
city: Toms River
country: United States
facility: New Jersey Hematology and Oncology
state: New Jersey
city: New York
country: United States
facility: Weill Cornell Medical Center - Monitoring Location
state: New York
city: New York
country: United States
facility: Weill Cornell Medical Center
state: New York
city: Rochester
country: United States
facility: Strong Memorial Hospital
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Cincinnati
country: United States
facility: Oncology Hematology Care, Inc.
state: Ohio
city: Cincinnati
country: United States
facility: Oncology Hematology Care, Inc.
state: Ohio
city: Cincinnati
country: United States
facility: Oncology Hematology Care Inc - USOR
state: Ohio
city: Cincinnati
country: United States
facility: Oncology Hematology Care Inc - USOR
state: Ohio
city: Cleveland
country: United States
facility: Fairview Hospital
state: Ohio
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Fairfield
country: United States
facility: Oncology Hematology Care, Inc - Fairfield
state: Ohio
city: Mayfield
country: United States
facility: Hillcrest Hospital Cancer Care Center
state: Ohio
city: Bethlehem
country: United States
facility: St. Luke's Hospital
state: Pennsylvania
city: Easton
country: United States
facility: St. Luke's University Health Network
state: Pennsylvania
city: Easley
country: United States
facility: Greenville Health System
state: South Carolina
city: Greenville
country: United States
facility: Greenville Health System
state: South Carolina
city: Greenville
country: United States
facility: Greenville Health System Cancer Institute
state: South Carolina
city: Greer
country: United States
facility: Greenville Health System
state: South Carolina
city: Seneca
country: United States
facility: Greenville Health System
state: South Carolina
city: Spartanburg
country: United States
facility: Greenville Health System
state: South Carolina
city: Dickson
country: United States
facility: Tennessee Oncology - DICKSON - SCRI - PPDS
state: Tennessee
city: Franklin
country: United States
facility: Tennessee Oncology - FRANKLIN - SCRI - PPDS
state: Tennessee
city: Gallatin
country: United States
facility: Tennessee Oncology - GALLATIN - SCRI - PPDS
state: Tennessee
city: Hermitage
country: United States
facility: Tennessee Oncology - SUMMIT - SCRI - PPDS
state: Tennessee
city: Lebanon
country: United States
facility: Tennessee Oncology - LEBANON - SCRI - PPDS
state: Tennessee
city: Murfreesboro
country: United States
facility: Tennessee Oncology - MURFREESBORO - SCRI - PPDS
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Center for Blood Centers - SCRI - PPDS
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncolgy - BAPTIST - SCRI - PPDS
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology NASH - SCRI - PPDS
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology - ST THOMAS WEST - SCRI - PPDS
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology SKYLINE - SCRI - PPDS
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology - SOUTHERN HILLS - SCRI - PPDS
state: Tennessee
city: Shelbyville
country: United States
facility: Tennessee Oncology - SHELBYVILLE - SCRI - PPDS
state: Tennessee
city: Smyrna
country: United States
facility: Tennessee Oncology - SMYRNA - SCRI - PPDS
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology (West 38) - USOR
state: Texas
city: Austin
country: United States
facility: Texas Oncology (Balcones) - USOR
state: Texas
city: Austin
country: United States
facility: Texas Oncology (James Casey) - USOR
state: Texas
city: Dallas
country: United States
facility: Texas Oncology (Medical City) - USOR
state: Texas
city: Dallas
country: United States
facility: Baylor Sammons Cancer Center
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Longview
country: United States
facility: Texas Oncology (Tyler) - USOR
state: Texas
city: New Braunfels
country: United States
facility: Texas Oncology (E Common) - USOR
state: Texas
city: Round Rock
country: United States
facility: Texas Oncology (Round Rock) - USOR
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology - San Antonio Medical Center - USOR
state: Texas
city: Tyler
country: United States
facility: Texas Oncology (Tyler) - USOR
state: Texas
city: Blacksburg
country: United States
facility: Oncology and Hematology Associates of Southwest Virginia (Blacksburg) - USOR
state: Virginia
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Low Moor
country: United States
facility: Oncology and Hematology Associates of Southwest Virginia (Low Moor) - USOR
state: Virginia
city: Roanoke
country: United States
facility: Oncology and Hematology Associates of Southwest Virginia (Roanoke) - USOR
state: Virginia
city: Salem
country: United States
facility: Oncology and Hematology Associates of Southwest Virginia Inc
state: Virginia
city: Wytheville
country: United States
facility: Oncology and Hematology Associates of Southwest Virginia
state: Virginia
city: Auchenflower
country: Australia
facility: Icon Cancer Care Wesley
state: Queensland
city: Chermside
country: Australia
facility: Icon Cancer Care Chermside
state: Queensland
city: South Brisbane
country: Australia
facility: Icon Cancer Care South Brisbane
state: Queensland
city: South Brisbane
country: Australia
facility: Icon Cancer Care
state: Queensland
city: Southport
country: Australia
facility: Icon Cancer Care Southport
state: Queensland
city: Hobart
country: Australia
facility: Royal Hobart Hospital
state: Tasmania
city: Liverpool
country: Australia
facility: Liverpool Hospital
city: Brasschaat
country: Belgium
facility: Algemeen Ziekenhuis Klina
state: Antwerpen
city: Yvoir
country: Belgium
facility: CHU UCL Namur asbl - Site Godinne
state: Namur
city: Brugge
country: Belgium
facility: AZ Sint-Jan AV
state: West-Vlaanderen
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Leuven
country: Belgium
facility: UZ Leuven
city: Curitiba
country: Brazil
facility: Liga Paranaense de Combate Ao Cancer - Hospital Erasto Gaertner
state: Parana
city: Natal
country: Brazil
facility: Liga Norte Riograndense Contra O Cancer
state: Rio Grande Do Norte
city: Florianopolis
country: Brazil
facility: Centro de Pesquisas Oncologicas
state: Santa Catarina
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre (HCPA) - PPDS
city: Rio De Janeiro
country: Brazil
facility: Universidade Federal do Rio de Janeiro - UFRJ
city: Sao Paulo
country: Brazil
facility: Hospital Santa Marcelina
city: Sao Paulo
country: Brazil
facility: Hospital Santa Marcelina
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Edmonton
country: Canada
facility: Kaye Edmonton Clinic
state: Alberta
city: Saint John
country: Canada
facility: Saint John Regional Hospital
state: New Brunswick
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Beijing
country: China
facility: Xuanwu Hospital Capital Medical University
state: Beijing
city: Tianjin
country: China
facility: Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences
state: Tianjin
city: Hradec Kralove
country: Czechia
facility: Fakultni nemocnice Hradec Kralove
state: Kralovehradeck Kraj
city: Prague
country: Czechia
facility: Vseobecna Fakultni Nemocnice V Praze
city: Praha
country: Czechia
facility: Fakultni nemocnice Kralovske Vinohrady
city: Caen
country: France
facility: Hopital Cote de Nacre
state: Calvados
city: Angers
country: France
facility: CHU Angers
state: Maine-et-Loire
city: Le Mans
country: France
facility: Centre Hospitalier Le Mans
city: Paris
country: France
facility: Hopital Saint Louis
city: Paris
country: France
facility: Hopital Saint Louis
city: Tubingen
country: Germany
facility: Universitatsklinikum Tubingen
state: Baden-Wurttemberg
city: Leipzig
country: Germany
facility: Universitatsklinikum Leipzig
state: Sachsen
city: Dresden
country: Germany
facility: Universitatsklinikum Carl Gustav Carus an der TU Dresden
city: Dusseldorf
country: Germany
facility: Marien Hospital Akademisches Lehrkrankenhaus
city: Athens
country: Greece
facility: Laiko General Hospital of Athens
state: Attiki
city: Athens
country: Greece
facility: Athens General Hospital 'G Gennimatas'
state: Attiki
city: Athens
country: Greece
facility: Attikon University General Hospital
state: Attiki
city: Alexandroupolis
country: Greece
facility: University Hospital of Alexandroupolis
city: Athens
country: Greece
facility: Laiko General Hospital of Athens
city: Ioannina
country: Greece
facility: University General Hospital of Ioannina
city: Larissa
country: Greece
facility: University General Hospital of Larissa
city: Patras
country: Greece
facility: University General Hospital of Patras
city: Thessaloniki
country: Greece
facility: Georgios Papanikolaou General Hospital of Thessaloniki
city: Holon
country: Israel
facility: Edith Wolfson Medical Center
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center PPDS -
city: Nahariya
country: Israel
facility: Galilee Medical Center
city: Safed
country: Israel
facility: ZIV Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center PPDS
city: Bologna
country: Italy
facility: Azienda Ospedaliero Universitaria Di Bologna - Policlinico S Orsola Malpighi
state: Emilia-Romagna
city: Brescia
country: Italy
facility: ASST degli Spedali Civili di Brescia - Spedali Civili di Brescia - INCIPIT - PIN
state: Lombardia
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi
city: Rionero in Vulture
country: Italy
facility: IRCCS Centro Di Riferimento Oncologico Della Basilicata
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
city: Torino
country: Italy
facility: Azienda Ospedaliero Universitaria San Giovanni Battista Di Torino
city: Fukuyama
country: Japan
facility: Japan Mutual Aid Association of Public School Teachers Chugoku Central Hospital
state: Hirosima
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
state: Hokkaido
city: Fukushima-shi
country: Japan
facility: Fukushima Medical University Hospital
state: Hukusima
city: Kobe-City
country: Japan
facility: Kobe City Medical Center General Hospital
state: Hyogo
city: Kyoto-shi
country: Japan
facility: University Hospital, Kyoto Prefectural University of Medicine
state: Kyoto
city: Osakasayama
country: Japan
facility: Kindai University Hospital
state: Osaka
city: Kawagoe
country: Japan
facility: Saitama Medical Center
state: Saitama
city: Bunkyo
country: Japan
facility: Juntendo University Hospital
state: Tokyo
city: Shinagawa-ku
country: Japan
facility: NTT Medical Center Tokyo
state: Tokyo
city: Fukuoka-city
country: Japan
facility: Kyushu University Hospital
city: Mibu
country: Japan
facility: Dokkyo Medical University Hospital
city: Nagasaki
country: Japan
facility: Nagasaki University Hospital
city: Osaka
country: Japan
facility: Osaka Metropolitan University Hospital
city: Yokohama-shi
country: Japan
facility: Yokohama City University Hospital
city: Yoshida-gun
country: Japan
facility: University of Fukui Hospital
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
city: Jeongnam
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center - PPDS
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center - PPDS
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Mary's Hospital
city: Huixquilucan
country: Mexico
facility: Hematologica Alta Especialidad S.C.
city: Mexico
country: Mexico
facility: Capital Humano para Investigacion Clinica SC
city: Warszawa
country: Poland
facility: Instytut Hematologii i Transfuzjologii
state: Mazowieckie
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne, Klinika Hematologii I Transplantologii, Budynek Centrum Medycyny N
state: Pomorskie
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
state: Pomorskie
city: Kielce
country: Poland
facility: Swietokrzyskie Centrum Onkologii
state: Swietokrzyskie
city: Lublin
country: Poland
facility: Centrum Onkologii Ziemi Lubelskiej
city: Opole
country: Poland
facility: Zaklad Diagnostyki Obrazowej SOR
city: Opole
country: Poland
facility: Szpital Wojewodzki w Opolu
city: Moscow
country: Russian Federation
facility: City Clinical Hospital # 40
city: Saint Petersburg
country: Russian Federation
facility: North-West Federal Medical Research Center n.a. V.A. Almazov
city: St. Petersburg
country: Russian Federation
facility: Russian Research Institute of Hematology and Blood Transfusion
city: LHospitalet de Llobregat
country: Spain
facility: ICO lHospitalet Hospital Duran i Reynals
state: Barcelona
city: Leon
country: Spain
facility: Complejo Asistencial Universitario de Leon
state: Castilla Y Leon
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron - PPDS
city: Madrid
country: Spain
facility: Hospital Universitario de La Princesa
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario La Paz - PPDS
city: Salamanca
country: Spain
facility: Complejo Asistencial Universitario de Salamanca - H. Clinico
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia
city: Ankara
country: Turkey
facility: Gazi University Medical Faculty Gazi Hospital
city: Izmir
country: Turkey
facility: Ege University Medical Faculty
city: Mersin
country: Turkey
facility: Mersin University Medical Faculty
city: Samsun
country: Turkey
facility: Ondokuz Mayis Universitesi Tip Fakultesi Hastanesi
city: Tekirdag
country: Turkey
facility: Namik Kemal University
city: Trabzon
country: Turkey
facility: Karadeniz Technical University Faculty of Medicine
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital
state: Dorset
city: Maidstone
country: United Kingdom
facility: Maidstone Hospital
state: Kent
city: London
country: United Kingdom
facility: St Bartholomew's Hospital
city: Swansea
country: United Kingdom
facility: Singleton Hospital - PPDS
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Ades L, Girshova L, Doronin VA, Diez-Campelo M, Valcarcel D, Kambhampati S, Viniou NA, Woszczyk D, De Paz Arias R, Symeonidis A, Anagnostopoulos A, Munhoz EC, Platzbecker U, Santini V, Fram RJ, Yuan Y, Friedlander S, Faller DV, Sekeres MA. Pevonedistat plus azacitidine vs azacitidine alone in higher-risk MDS/chronic myelomonocytic leukemia or low-blast-percentage AML. Blood Adv. 2022 Sep 13;6(17):5132-5145. doi: 10.1182/bloodadvances.2022007334.