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)



Status:Recruiting
Conditions:Cancer, Blood Cancer, Blood Cancer, Blood Cancer, Blood Cancer, Hematology
Therapuetic Areas:Hematology, Oncology
Healthy:No
Age Range:18 - Any
Updated:3/21/2019
Start Date:November 28, 2017
End Date:March 31, 2023
Contact:Takeda Study Registration Call Center
Email:GlobalOncologyMedinfo@takeda.com
Phone:+1-866-835-2233

Use our guide to learn which trials are right for you!

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

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).

The drug being tested in this study is called pevonedistat. Pevonedistat is being tested to
treat people with higher-risk myelodysplastic syndromes (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 worldwide. 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 or relapse from CR (for participants with low-blast
AML at study enrollment).

Inclusion Criteria:

1. Has morphologically confirmed diagnosis of myelodysplastic syndromes (MDS) or CMML
(i.e., with white blood cell [WBC] <13,000/μL) 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/ microliter (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.
We found this trial at
118
sites
13001 North Kendall Drive
Miami, Florida 33125
?
mi
from
Miami, FL
Click here to add this to my saved trials
Chapel Hill, North Carolina 27599
(919) 962-2211
University of North Carolina at Chapel Hill Carolina’s vibrant people and programs attest to the...
?
mi
from
Chapel Hill, NC
Click here to add this to my saved trials
9500 Euclid Avenue
Cleveland, Ohio 44106
216.444.2200
Cleveland Clinic Cleveland Clinic is committed to principles as presented in the United Nations Global...
?
mi
from
Cleveland, OH
Click here to add this to my saved trials
1601 Northwest 12th Avenue
Miami, Florida 33136
(305) 243-6545
University of Miami Miller School of Medicine The University of Miami Leonard M. Miller School...
?
mi
from
Miami, FL
Click here to add this to my saved trials
2950 Cleveland Clinic Blvd.
Weston, Florida 33331
866.293.7866
Cleveland Clinic Florida Cleveland Clinic Florida, located in Weston, West Palm Beach, Palm Beach Gardens...
?
mi
from
Weston, FL
Click here to add this to my saved trials
Altamonte Springs, Florida 32701
?
mi
from
Altamonte Springs, FL
Click here to add this to my saved trials
1365 Clifton Rd NE
Atlanta, Georgia 30322
(404) 778-1900
Winship Cancer Institute at Emory University Winship Cancer Institute of Emory University is Georgia
?
mi
from
Atlanta, GA
Click here to add this to my saved trials
40 Chasely Street
Auchenflower, Queensland 4066
?
mi
from
Auchenflower,
Click here to add this to my saved trials
1700 South Potomac Street
Aurora, Colorado 80012
?
mi
from
Aurora, CO
Click here to add this to my saved trials
901 West 38th Street
Austin, Texas 78705
?
mi
from
Austin, TX
Click here to add this to my saved trials
6204 Balcones Drive
Austin, Texas 78731
?
mi
from
Austin, TX
Click here to add this to my saved trials
4101 James Casey Street
Austin, Texas 78745
?
mi
from
Austin, TX
Click here to add this to my saved trials
Bethlehem, Pennsylvania 18015
?
mi
from
Bethlehem, PA
Click here to add this to my saved trials
2600 Research Center Drive
Blacksburg, Virginia 24060
?
mi
from
Blacksburg, VA
Click here to add this to my saved trials
1055 N Curtis Rd
Boise, Idaho 83706
(208) 367-2121
Saint Alphonsus Regional Medical Center Saint Alphonsus Health System is a four-hospital regional, faith-based Catholic...
?
mi
from
Boise, ID
Click here to add this to my saved trials
Bonita Springs, Florida 34135
?
mi
from
Bonita Springs, FL
Click here to add this to my saved trials
4715 Arapahoe Avenue
Boulder, Colorado 80303
?
mi
from
Boulder, CO
Click here to add this to my saved trials
Bradenton, Florida 34209
?
mi
from
Bradenton, FL
Click here to add this to my saved trials
Brandon, Florida 33511
?
mi
from
Brandon, FL
Click here to add this to my saved trials
?
mi
from
Brick, NJ
Click here to add this to my saved trials
Caldwell, New Jersey 83605
?
mi
from
Caldwell, NJ
Click here to add this to my saved trials
Cape Coral, Florida 33914
?
mi
from
Cape Coral, FL
Click here to add this to my saved trials
Charlottesville, Virginia 22903
(434) 924-0311
University of Virginia The University of Virginia is distinctive among institutions of higher education. Founded...
?
mi
from
Charlottesville, VA
Click here to add this to my saved trials
1653 W. Congress Parkway
Chicago, Illinois 60612
(312) 942-5000
Rush University Medical Center Rush University Medical Center encompasses a 664-bed hospital serving adults and...
?
mi
from
Chicago, IL
Click here to add this to my saved trials
4350 Malsbary Road
Cincinnati, Ohio 45242
?
mi
from
Cincinnati, OH
Click here to add this to my saved trials
5053 Wooster Rd
Cincinnati, Ohio 45226
(513) 751-2273
Oncology Hematology Care Our more than 60 physicians and advanced practice providers throughout neighborhood offices...
?
mi
from
Cincinnati, OH
Click here to add this to my saved trials
Clearwater, Florida 33761
?
mi
from
Clearwater, FL
Click here to add this to my saved trials
Cleveland, Ohio 44111
?
mi
from
Cleveland, OH
Click here to add this to my saved trials
2312 North Nevada Avenue
Colorado Springs, Colorado 80907
?
mi
from
Colorado Springs, CO
Click here to add this to my saved trials
?
mi
from
Corona, CA
Click here to add this to my saved trials
7777 Forest Lane
Dallas, Texas 75230
?
mi
from
Dallas, TX
Click here to add this to my saved trials
Dallas, Texas 75246
?
mi
from
Dallas, TX
Click here to add this to my saved trials
1801 Inwood Rd
Dallas, Texas 75390
(214) 645-3300
University of Texas Southwestern Medical Center UT Southwestern is an academic medical center, world-renowned for...
?
mi
from
Dallas, TX
Click here to add this to my saved trials
Daphne, Alabama 36526
?
mi
from
Daphne, AL
Click here to add this to my saved trials
1800 North Williams Street
Denver, Colorado 80218
?
mi
from
Denver, CO
Click here to add this to my saved trials
4700 East Hale Parkway
Denver, Colorado 80220
?
mi
from
Denver, CO
Click here to add this to my saved trials
Denver, Colorado 80209
?
mi
from
Denver, CO
Click here to add this to my saved trials
?
mi
from
Denver, CO
Click here to add this to my saved trials
Denver, Colorado 80239
?
mi
from
Denver, CO
Click here to add this to my saved trials
1721 East 19th Ave., Suite #200 & #300
Denver, Colorado 80218
720-754-4800
Colorado Blood Cancer Institute When patients come to the Colorado Blood Cancer Institute, the entire...
?
mi
from
Denver, CO
Click here to add this to my saved trials
Dickson, Tennessee 37055
?
mi
from
Dickson, TN
Click here to add this to my saved trials
Easley, South Carolina 29640
?
mi
from
Easley, SC
Click here to add this to my saved trials
Easton, Pennsylvania 18045
?
mi
from
Easton, PA
Click here to add this to my saved trials
Englewood, Colorado 80112
?
mi
from
Englewood, CO
Click here to add this to my saved trials
Fairfield, Ohio 45014
?
mi
from
Fairfield, OH
Click here to add this to my saved trials
4371 Veronica S Shoemaker Boulevard
Fort Myers, Florida 33916
?
mi
from
Fort Myers, FL
Click here to add this to my saved trials
Fountain Valley, California 92708
?
mi
from
Fountain Valley, CA
Click here to add this to my saved trials
Franklin, Tennessee 37067
?
mi
from
Franklin, TN
Click here to add this to my saved trials
Gainesville, Florida 32605
?
mi
from
Gainesville, FL
Click here to add this to my saved trials
Gallatin, Tennessee 37066
?
mi
from
Gallatin, TN
Click here to add this to my saved trials
Goodyear, Arizona 85338
?
mi
from
Goodyear, AZ
Click here to add this to my saved trials
Greenville, South Carolina 29605
?
mi
from
Greenville, SC
Click here to add this to my saved trials
Greenville, South Carolina 29615
?
mi
from
Greenville, SC
Click here to add this to my saved trials
Greer, South Carolina 29650
?
mi
from
Greer, SC
Click here to add this to my saved trials
Hackensack, New Jersey 07601
?
mi
from
Hackensack, NJ
Click here to add this to my saved trials
Hermitage, Tennessee 37076
?
mi
from
Hermitage, TN
Click here to add this to my saved trials
Independence, Missouri 64057
?
mi
from
Independence, MO
Click here to add this to my saved trials
4500 San Pablo Road South
Jacksonville, Florida 32224
?
mi
from
Jacksonville, FL
Click here to add this to my saved trials
2316 E Meyer Blvd
Kansas City, Missouri 64132
(816) 276-4000
Research Medical Center Research Medical Center offers hospital and health clinic services across three Kansas...
?
mi
from
Kansas City, MO
Click here to add this to my saved trials
Kansas City, Missouri 64131
?
mi
from
Kansas City, MO
Click here to add this to my saved trials
3855 Health Sciences Dr,
La Jolla, California 92093
(858) 822-6100
UC San Diego Moores Cancer Center Established in 1978, UC San Diego Moores Cancer Center...
?
mi
from
La Jolla, CA
Click here to add this to my saved trials
11750 West 2nd Place
Lakewood, Colorado 80228
?
mi
from
Lakewood, CO
Click here to add this to my saved trials
?
mi
from
Largo, FL
Click here to add this to my saved trials
Lebanon, Tennessee 37087
?
mi
from
Lebanon, TN
Click here to add this to my saved trials
Lecanto, Florida 34461
?
mi
from
Lecanto, FL
Click here to add this to my saved trials
22 West Dry Creek Circle
Littleton, Colorado 80120
?
mi
from
Littleton, CO
Click here to add this to my saved trials
10107 RidgeGate Parkway
Lone Tree, Colorado 80124
?
mi
from
Lone Tree, CO
Click here to add this to my saved trials
2030 Mountain View Avenue
Longmont, Colorado 80501
?
mi
from
Longmont, CO
Click here to add this to my saved trials
910 East Houston Street
Longview, Texas 75601
?
mi
from
Longview, TX
Click here to add this to my saved trials
?
mi
from
Low Moor, VA
Click here to add this to my saved trials
?
mi
from
Mayfield, OH
Click here to add this to my saved trials
Mobile, Alabama 36608
?
mi
from
Mobile, AL
Click here to add this to my saved trials
Murfreesboro, Tennessee 37130
?
mi
from
Murfreesboro, TN
Click here to add this to my saved trials
Nampa, Idaho 83687
?
mi
from
Nampa, ID
Click here to add this to my saved trials
?
mi
from
Naples, FL
Click here to add this to my saved trials
Nashville, Tennessee 37203
?
mi
from
Nashville, TN
Click here to add this to my saved trials
1100 Charlotte Avenue
Nashville, Tennessee 37203
?
mi
from
Nashville, TN
Click here to add this to my saved trials
Nashville, Tennessee 37205
?
mi
from
Nashville, TN
Click here to add this to my saved trials
Nashville, Tennessee 37207
?
mi
from
Nashville, TN
Click here to add this to my saved trials
Nashville, Tennessee 37211
?
mi
from
Nashville, TN
Click here to add this to my saved trials
1448 East Common Street
New Braunfels, Texas 78130
?
mi
from
New Braunfels, TX
Click here to add this to my saved trials
New Port Richey, Florida 34655
?
mi
from
New Port Richey, FL
Click here to add this to my saved trials
New York, New York 10065
?
mi
from
New York, NY
Click here to add this to my saved trials
?
mi
from
Ocala, FL
Click here to add this to my saved trials
Omaha, Nebraska 68114
?
mi
from
Omaha, NE
Click here to add this to my saved trials
Orange City, Florida 32763
?
mi
from
Orange City, FL
Click here to add this to my saved trials
Orlando, Florida 32806
?
mi
from
Orlando, FL
Click here to add this to my saved trials
5721 W 119th St
Overland Park, Kansas 66209
(913) 498-6000
Menorah Medical Center Menorah Medical Center (MMC), a full-service, acute care hospital located on the...
?
mi
from
Overland Park, KS
Click here to add this to my saved trials
9397 Crown Crest Boulevard
Parker, Colorado 80138
?
mi
from
Parker, CO
Click here to add this to my saved trials
Port Charlotte, Florida 33980
?
mi
from
Port Charlotte, FL
Click here to add this to my saved trials
3676 Parker Boulevard
Pueblo, Colorado 81008
?
mi
from
Pueblo, CO
Click here to add this to my saved trials
7000 Boulder Avenue
Redlands, California 92373
?
mi
from
Redlands, CA
Click here to add this to my saved trials
?
mi
from
Riverside, CA
Click here to add this to my saved trials
2013 Jefferson Street Southwest
Roanoke, Virginia 24014
?
mi
from
Roanoke, VA
Click here to add this to my saved trials
Rochester, New York 14642
?
mi
from
Rochester, NY
Click here to add this to my saved trials
2410 Round Rock Ave
Round Rock, Texas 78681
?
mi
from
Round Rock, TX
Click here to add this to my saved trials
Saint Petersburg, Florida 33705
?
mi
from
Saint Petersburg, FL
Click here to add this to my saved trials
?
mi
from
Salem, VA
Click here to add this to my saved trials
5206 Research Drive
San Antonio, Texas 78240
?
mi
from
San Antonio, TX
Click here to add this to my saved trials
Sarasota, Florida 34232
?
mi
from
Sarasota, FL
Click here to add this to my saved trials
Seneca, South Carolina 29672
?
mi
from
Seneca, SC
Click here to add this to my saved trials