Acute Myeloid Leukemia Clinical Trial
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)
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).
Full 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:
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).
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.
Eastern Cooperative Oncology Group (ECOG) status of 0, 1, or 2.
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:
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.
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.
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.
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).
Has either clinical evidence of or history of central nervous system involvement by AML.
Has active uncontrolled infection or severe infectious disease, such as severe pneumonia, meningitis, or septicemia.
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.
Has nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone resection.
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.
Has known human immunodeficiency virus (HIV) seropositive.
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.
Has known hepatic cirrhosis or severe preexisting hepatic impairment.
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.
Has treatment with strong cytochrome P 3A (CYP3A) inducers within 14 days before the first dose of pevonedistat.
Check Your Eligibility
Let’s see if you might be eligible for this study.
What is your age and gender ?
There are 228 Locations for this study
Daphne Alabama, 36526, United States
Mobile Alabama, 36607, United States
Mobile Alabama, 36608, United States
Mobile Alabama, 36608, United States
Goodyear Arizona, 85338, United States
Tucson Arizona, 85704, United States
Tucson Arizona, 85704, United States
Tucson Arizona, 85711, United States
Corona California, 92879, United States
Fountain Valley California, 92708, United States
La Jolla California, 92093, United States
Redlands California, 92373, United States
Riverside California, 92501, United States
Aurora Colorado, 80012, United States
Boulder Colorado, 80303, United States
Colorado Springs Colorado, 80907, United States
Denver Colorado, 80209, United States
Denver Colorado, 80218, United States
Denver Colorado, 80218, United States
Denver Colorado, 80218, United States
Denver Colorado, 80218, United States
Denver Colorado, 80220, United States
Denver Colorado, 80239, United States
Englewood Colorado, 80112, United States
Lakewood Colorado, 80228, United States
Littleton Colorado, 80120, United States
Lone Tree Colorado, 80124, United States
Longmont Colorado, 80501, United States
Parker Colorado, 80138, United States
Pueblo Colorado, 81008, United States
Thornton Colorado, 80260, United States
Washington District of Columbia, 20010, United States
Altamonte Springs Florida, 32701, United States
Bonita Springs Florida, 34135, United States
Bradenton Florida, 34209, United States
Brandon Florida, 33511, United States
Cape Coral Florida, 33914, United States
Clearwater Florida, 33761, United States
Fort Myers Florida, 33905, United States
Fort Myers Florida, 33908, United States
Fort Myers Florida, 33916, United States
Gainesville Florida, 32605, United States
Jacksonville Florida, 32224, United States
Largo Florida, 33770, United States
Lecanto Florida, 34461, United States
Miami Florida, 33136, United States
Miami Florida, 33176, United States
Naples Florida, 34102, United States
New Port Richey Florida, 34655, United States
Ocala Florida, 34471, United States
Orange City Florida, 32763, United States
Orlando Florida, 32806, United States
Port Charlotte Florida, 33980, United States
Saint Petersburg Florida, 33705, United States
Sarasota Florida, 34232, United States
Sarasota Florida, 34236, United States
Spring Hill Florida, 34608, United States
Tampa Florida, 33607, United States
Tavares Florida, 32778, United States
The Villages Florida, 32159, United States
Venice Florida, 34285, United States
Venice Florida, 34292, United States
Weston Florida, 33331, United States
Winter Park Florida, 32792, United States
Atlanta Georgia, 30322, United States
Boise Idaho, 83706, United States
Caldwell Idaho, 83605, United States
Nampa Idaho, 83687, United States
Chicago Illinois, 60612, United States
Overland Park Kansas, 66209, United States
Independence Missouri, 64057, United States
Kansas City Missouri, 64132, United States
Kansas City Missouri, 64132, United States
Omaha Nebraska, 68130, United States
Brick New Jersey, 08724, United States
Hackensack New Jersey, 07601, United States
Toms River New Jersey, 08755, United States
New York New York, 10021, United States
New York New York, 10021, United States
Rochester New York, 14642, United States
Chapel Hill North Carolina, 27599, United States
Cincinnati Ohio, 45211, United States
Cincinnati Ohio, 45230, United States
Cincinnati Ohio, 45236, United States
Cincinnati Ohio, 45242, United States
Cleveland Ohio, 44111, United States
Cleveland Ohio, 44195, United States
Fairfield Ohio, 45014, United States
Mayfield Ohio, 44124, United States
Bethlehem Pennsylvania, 18015, United States
Easton Pennsylvania, 18045, United States
Easley South Carolina, 29640, United States
Greenville South Carolina, 29605, United States
Greenville South Carolina, 29615, United States
Greer South Carolina, 29650, United States
Seneca South Carolina, 29672, United States
Spartanburg South Carolina, 29307, United States
Dickson Tennessee, 37055, United States
Franklin Tennessee, 37067, United States
Gallatin Tennessee, 37066, United States
Hermitage Tennessee, 37076, United States
Lebanon Tennessee, 37090, United States
Murfreesboro Tennessee, 37129, United States
Nashville Tennessee, 37203, United States
Nashville Tennessee, 37203, United States
Nashville Tennessee, 37203, United States
Nashville Tennessee, 37205, United States
Nashville Tennessee, 37207, United States
Nashville Tennessee, 37211, United States
Shelbyville Tennessee, 37160, United States
Smyrna Tennessee, 37167, United States
Austin Texas, 78705, United States
Austin Texas, 78731, United States
Austin Texas, 78745, United States
Dallas Texas, 75230, United States
Dallas Texas, 75246, United States
Dallas Texas, 75390, United States
Longview Texas, 75601, United States
New Braunfels Texas, 78130, United States
Round Rock Texas, 78681, United States
San Antonio Texas, 78240, United States
Tyler Texas, 75702, United States
Blacksburg Virginia, 24060, United States
Charlottesville Virginia, 22903, United States
Low Moor Virginia, 24457, United States
Roanoke Virginia, 24014, United States
Salem Virginia, 24153, United States
Wytheville Virginia, 24382, United States
Auchenflower Queensland, 4066, Australia
Chermside Queensland, 4032, Australia
South Brisbane Queensland, 4101, Australia
South Brisbane Queensland, 4101, Australia
Southport Queensland, 4215, Australia
Hobart Tasmania, 7000, Australia
Liverpool , 1871, Australia
Brasschaat Antwerpen, 2930, Belgium
Yvoir Namur, 5530, Belgium
Brugge West-Vlaanderen, 8000, Belgium
Bruxelles , 1200, Belgium
Leuven , 3000, Belgium
Curitiba Parana, 81520, Brazil
Natal Rio Grande Do Norte, 59075, Brazil
Florianopolis Santa Catarina, 88034, Brazil
Porto Alegre , 90035, Brazil
Rio De Janeiro , 21941, Brazil
Sao Paulo , 08270, Brazil
Sao Paulo , 08270, Brazil
Calgary Alberta, T2N 4, Canada
Edmonton Alberta, T6G 2, Canada
Edmonton Alberta, T6G1Z, Canada
Saint John New Brunswick, E2L 4, Canada
Toronto Ontario, M4N3M, Canada
Toronto Ontario, M5G 2, Canada
Toronto Ontario, M5G2M, Canada
Beijing Beijing, 10005, China
Tianjin Tianjin, 30002, China
Hradec Kralove Kralovehradeck Kraj, 500 0, Czechia
Prague , 128 0, Czechia
Praha , 100 3, Czechia
Caen Calvados, 14033, France
Angers Maine-et-Loire, 49100, France
Le Mans , 74000, France
Paris , 75010, France
Paris , 75475, France
Tubingen Baden-Wurttemberg, 72076, Germany
Leipzig Sachsen, 4103, Germany
Dresden , 1307, Germany
Dusseldorf , 40479, Germany
Athens Attiki, 115 2, Greece
Athens Attiki, 11527, Greece
Athens Attiki, 12462, Greece
Alexandroupolis , 68100, Greece
Athens , 11527, Greece
Ioannina , 45500, Greece
Larissa , 41110, Greece
Patras , 26504, Greece
Thessaloniki , 57010, Greece
Holon , 58100, Israel
Jerusalem , 91031, Israel
Jerusalem , 91120, Israel
Nahariya , , Israel
Safed , 13100, Israel
Tel Aviv , 64239, Israel
Bologna Emilia-Romagna, 40138, Italy
Brescia Lombardia, 25123, Italy
Firenze , 50134, Italy
Rionero in Vulture , 85028, Italy
Rozzano , 20089, Italy
Torino , 10126, Italy
Fukuyama Hirosima, 720-0, Japan
Sapporo Hokkaido, 060 8, Japan
Fukushima-shi Hukusima, 960-1, Japan
Kobe-City Hyogo, 650-0, Japan
Kyoto-shi Kyoto, 602-8, Japan
Osakasayama Osaka, 589-8, Japan
Kawagoe Saitama, 35085, Japan
Bunkyo Tokyo, 113-8, Japan
Shinagawa-ku Tokyo, 141-8, Japan
Fukuoka-city , 812-8, Japan
Mibu , 321-0, Japan
Nagasaki , 85281, Japan
Osaka , 545-8, Japan
Yokohama-shi , 232-0, Japan
Yoshida-gun , 910-1, Japan
Busan , 49241, Korea, Republic of
Daegu , 41944, Korea, Republic of
Jeongnam , 58128, Korea, Republic of
Seoul , 5505, Korea, Republic of
Seoul , 6351, Korea, Republic of
Seoul , 6591, Korea, Republic of
Huixquilucan , 52787, Mexico
Mexico , , Mexico
Warszawa Mazowieckie, 02-77, Poland
Gdansk Pomorskie, 80-21, Poland
Gdansk Pomorskie, 80-95, Poland
Kielce Swietokrzyskie, 25-73, Poland
Lublin , 20-09, Poland
Opole , 45-06, Poland
Opole , 45-37, Poland
Moscow , 12930, Russian Federation
Saint Petersburg , 19734, Russian Federation
St. Petersburg , 19102, Russian Federation
LHospitalet de Llobregat Barcelona, 8907, Spain
Leon Castilla Y Leon, 24071, Spain
Barcelona , 8035, Spain
Madrid , 28006, Spain
Madrid , 28009, Spain
Madrid , 28034, Spain
Madrid , 28046, Spain
Salamanca , 37007, Spain
Valencia , 46010, Spain
Valencia , 46026, Spain
Ankara , 6500, Turkey
Izmir , 35100, Turkey
Mersin , 33343, Turkey
Samsun , 55139, Turkey
Tekirdag , 59100, Turkey
Trabzon , 61080, Turkey
Bournemouth Dorset, BH7 7, United Kingdom
Maidstone Kent, ME16 , United Kingdom
London , EC1A , United Kingdom
Swansea , SA2 8, United Kingdom
How clear is this clinincal trial information?