A Study of Venetoclax in Combination With Azacitidine Versus Azacitidine in Treatment Naïve Participants With Acute Myeloid Leukemia Who Are Ineligible for Standard Induction Therapy (Viale-a)

A Randomized, Double-Blind, Placebo Controlled Phase 3 Study of Venetoclax in Combination With Azacitidine Versus Azacitidine in Treatment Naïve Subjects With Acute Myeloid Leukemia Who Are Ineligible for Standard Induction Therapy

Acute Myeloid Leukaemia (AML) is an aggressive and rare cancer of myeloid cells (a white blood cell responsible for fighting infections). Successful treatment of AML is dependent on what subtype of AML the participant has, and the age of the participant when diagnosed.

Venetoclax is an experimental drug that kills cancer cells by blocking a protein (part of a cell) that allows cancer cells to stay alive. This study is designed to see if adding venetoclax to azacitidine works better than azacitidine on its own.

This is a Phase 3, randomized, double-blind (treatment is unknown to participants and doctors), placebo controlled study in patients with AML who are >= 18 or more years old and have not been treated before. Participants who take part in this study should not be suitable for standard induction therapy (usual starting treatment). AbbVie is funding this study which will take place at approximately 180 hospitals globally and enroll approximately 400 participants.

In this study, 2/3 of participants will receive venetoclax every day with azacitidine and the remaining 1/3 will receive placebo (dummy) tablets with azacitidine.

Participants will continue to have study visits and receive treatment for as long as they are having a clinical benefit. The effect of the treatment on AML will be checked by taking blood, bone marrow, scans, measuring side effects and by completing health questionnaires. Blood and bone marrow tests will be completed to see why some people respond better than others. Additional blood tests will be completed for genetic factors and to see how long the drug remains in the body.

Study Overview

• Status: Active, not recruiting
• Conditions: Acute Myeloid Leukemia (AML)
• Intervention / Treatment: Drug: Venetoclax; Drug: Placebo; Drug: Azacitidine

• Study Type: Interventional
• Enrollment (Actual): 443
• Phase: Phase 3

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital /ID# 154272
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital /ID# 154271
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Alfred Health /ID# 154275
    • Melbourne, Victoria, Australia, 3065
      • St Vincent's Hospital Melbourne /ID# 155094
    • Parkville, Victoria, Australia, 3050
      • The Royal Melbourne Hospital /ID# 155095
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Sir Charles Gairdner Hospital /ID# 163924
    • Perth, Western Australia, Australia, 6000
      • Royal Perth Hospital /ID# 154274
• Austria
  • Salzburg, Austria, 5020
    • Duplicate_Landeskrankenhaus Salzburg /ID# 169719
  • Wien, Austria, 1140
    • Hanusch Krankenhaus /ID# 155676
  • Niederoesterreich
    • Sankt Poelten, Niederoesterreich, Austria, 3100
      • Universitaetsklinikum St. Poelten /ID# 167436
  • Oberoesterreich
    • Linz, Oberoesterreich, Austria, 4010
      • Ordensklinikum Linz GmbH Barmherzige Schwestern /ID# 154888
    • Linz, Oberoesterreich, Austria, 4010
      • Ordensklinikum Linz GmbH Elisabethinen /ID# 154885
  • Steiermark
    • Graz, Steiermark, Austria, 8036
      • Medizinische Universitaet Graz /ID# 157882
• Belgium
  • Brugge, Belgium, 8000
    • AZ Sint-Jan Brugge /ID# 154041
  • Bruxelles-Capitale
    • Jette, Bruxelles-Capitale, Belgium, 1090
      • UZ Brussel /ID# 153393
    • Woluwe-Saint-Lambert, Bruxelles-Capitale, Belgium, 1200
      • UCL Saint-Luc /ID# 153391
  • Oost-Vlaanderen
    • Gent, Oost-Vlaanderen, Belgium, 9000
      • UZ Gent /ID# 153392
• Brazil
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-903
      • Hospital de Clinicas de Porto Alegre /ID# 157779
  • Sao Paulo
    • Ribeirão Preto, Sao Paulo, Brazil, 14051-140
      • Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto - USP /ID# 153099
    • São Paulo, Sao Paulo, Brazil, 01236-030
      • Instituto de Ensino e Pesquisa São Lucas /ID# 157778
    • São Paulo, Sao Paulo, Brazil, 01246-000
      • Instituto do Câncer do Estado de São Paulo - ICESP /ID# 153095
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre /ID# 159645
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • St. Paul's Hospital /ID# 159644
  • Ontario
    • Hamilton, Ontario, Canada, L8V 1C3
      • Juravinski Cancer Centre /ID# 153650
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hospital Research Institute /ID# 153541
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre /ID# 153651
• China
  • Jinan, China, 250012
    • Qilu Hospital of Shandong University /ID# 167485
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Fujian Medical University Union Hospital /ID# 167314
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Nanfang Hospital of Southern Medical University /ID# 170148
  • Hebei
    • Shijiazhuang, Hebei, China, 050000
      • The Second Hospital of Hebei Medical University /ID# 167316
  • Henan
    • Zhengzhou, Henan, China, 450008
      • Henan Cancer Hospital /ID# 167320
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Tongji Hospital Tongji Medical College Huazhong University of Science and Techno /ID# 167315
    • Wuhan, Hubei, China, 430022
      • Union Hospital Tongji Medical College Huazhong University of Science and Technol /ID# 167493
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Jiangsu Province Hospital /ID# 167489
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Hospital of Jilin University /ID# 167490
  • Shanghai
    • Shanghai, Shanghai, China, 200065
      • Ruijin Hospital, Shanghai Jiaotong University School of Medicine /ID# 167318
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital, Sichuan University /ID# 167492
  • Tianjin
    • Tianjin, Tianjin, China, 300020
      • Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sc /ID# 167487
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310006
      • The First Affiliated Hospital, Zhejiang University School of Medicine /ID# 167317
• Croatia
  • Grad Zagreb
    • Zagreb, Grad Zagreb, Croatia, 10000
      • Clinical Hospital Dubrava /ID# 153515
    • Zagreb, Grad Zagreb, Croatia, 10000
      • Klinicki bolnicki centar Zagreb /ID# 153383
  • Osjecko-baranjska Zupanija
    • Osijek, Osjecko-baranjska Zupanija, Croatia, 31000
      • Duplicate_Klinicki bolnicki centar Osijek /ID# 153623
• Czechia
  • Brno, Czechia, 625 00
    • Fakultni Nemocnice Brno /ID# 154019
  • Hradec Kralove, Czechia, 500 05
    • Fakultni nemocnice Hradec Kralove /ID# 154021
  • Ostrava, Czechia, 708 52
    • Fakultni nemocnice Ostrava /ID# 154017
  • Plzen, Czechia, 305 99
    • Fakultni nemocnice Plzen /ID# 154018
• Denmark
  • Nordjylland
    • Aalborg, Nordjylland, Denmark, 9000
      • Aalborg University Hospital /ID# 154047
• Finland
  • Turku, Finland, 20520
    • Turku University Hospital /ID# 154964
  • Pirkanmaa
    • Tampere, Pirkanmaa, Finland, 33520
      • Tampere University Hospital /ID# 154963
  • Uusimaa
    • Helsinki, Uusimaa, Finland, 00290
      • Helsinki University Hospital /ID# 155223
• France
  • Angers, France, 49933
    • Chu Angers /Id# 153792
  • Paris, France, 75010
    • AP-HP - Hopital Saint-Louis /ID# 153787
  • Toulouse Cedex 9, France, 31059
    • IUCT Oncopole /ID# 153788
  • Gironde
    • Pessac, Gironde, France, 33604
      • CHU Bordeaux - Hopital Haut Leveque /ID# 153789
• Germany
  • Halle (Saale), Germany, 06120
    • Universitaetsklinikum Halle (Saale) /ID# 153058
  • Hamburg, Germany, 20246
    • Universitaetsklinikum Hamburg-Eppendorf (UKE) /ID# 153056
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover /ID# 153055
  • Baden-Wuerttemberg
    • Ulm, Baden-Wuerttemberg, Germany, 89081
      • Universitaetsklinikum Ulm /ID# 153054
  • Hessen
    • Frankfurt am Main, Hessen, Germany, 60590
      • Universitaetsklinikum Frankfurt /ID# 153060
  • Nordrhein-Westfalen
    • Muenster, Nordrhein-Westfalen, Germany, 48149
      • Universitaetsklinikum Muenster /ID# 153059
• Hungary
  • Budapest, Hungary, 1085
    • Semmelweis Egyetem /ID# 153816
  • Budapest, Hungary, 1097
    • Del-pesti Centrumkorhaz Orszagos Hematologiai es Infektologiai Intezet /ID# 158990
  • Budapest, Hungary, 1088
    • Duplicate_Semmelweis Egyetem /ID# 153815
  • Csongrad
    • Szeged, Csongrad, Hungary, 6725
      • Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont /ID# 153812
  • Hajdu-Bihar
    • Debrecen, Hajdu-Bihar, Hungary, 4032
      • Debreceni Egyetem Klinikai Kozpont /ID# 153814
  • Nyiregyhaza
    • Nyíregyháza, Nyiregyhaza, Hungary, 4400
      • Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz Josa Andras Okta /ID# 169854
  • Somogy
    • Kaposvár, Somogy, Hungary, 7400
      • Somogy Megyei Kaposi Mor Oktato Korhaz /ID# 153813
• Israel
  • Be'er Ya'aqov, Israel, 70300
    • Assaf Harofeh Medical Center /ID# 158063
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus /ID# 154174
  • Jerusalem, Israel, 91120
    • Hadassah /ID# 154172
  • Petach Tikva, Israel, 4941492
    • Rabin Medical Center /ID# 154176
  • Tel-Aviv
    • Ramat Gan, Tel-Aviv, Israel, 5265601
      • The Chaim Sheba Medical Center /ID# 154173
    • Tel Aviv-Yafo, Tel-Aviv, Israel, 6423906
      • Tel Aviv Sourasky Medical Center /ID# 154175
• Italy
  • Ancona, Italy, 60126
    • Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona /ID# 171220
  • Bergamo, Italy, 24127
    • Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni /ID# 152875
  • Bologna, Italy, 40138
    • IRCCS Azienda Ospedaliero-Universitaria di Bologna /ID# 152883
  • Genova, Italy, 16132
    • Ospedale Policlinico San Martino /ID# 158104
  • Milan, Italy, 20122
    • Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico /ID# 152882
  • Napoli, Italy, 80131
    • Azienda Ospedaliera di Rilievo Nazionale Antonio Cardarelli /ID# 152879
  • Reggio Calabria, Italy, 89124
    • Grande Ospedale Metropolitano Bianchi Melacrino Morelli /ID# 152877
  • Rome, Italy, 00189
    • Azienda Ospedaliero-Universitaria Sant'Andrea /ID# 152876
  • Puglia
    • Lecce, Puglia, Italy, 73100
      • Presidio Ospedaliero Vito Fazzi /ID# 170837
  • Roma
    • Rome, Roma, Italy, 00133
      • Fondazione PTV Policlinico Tor Vergata /ID# 152881
• Japan
  • Aichi
    • Nagoya-shi, Aichi, Japan, 464-8681
      • Aichi Cancer Center Hospital /ID# 200824
  • Fukui
    • Yoshida-gun, Fukui, Japan, 910-1193
      • University of Fukui Hospital /ID# 167432
  • Fukuoka
    • Fukuoka-shi, Fukuoka, Japan, 811-1395
      • National Hospital Organization Kyushu Cancer Center /ID# 201111
    • Fukuoka-shi, Fukuoka, Japan, 812-8582
      • Kyushu University Hospital /ID# 169095
  • Gunma
    • Maebashi-shi, Gunma, Japan, 371-0821
      • Gunmaken Saiseikai Maebashi Hospital /ID# 168316
  • Ibaraki
    • Higashi, Ibaraki, Japan, 311-3193
      • National Hospital Organization Mito Medical Center /ID# 168219
    • Hitachi-shi, Ibaraki, Japan, 317-0077
      • Hitachi General Hospital /ID# 201109
  • Kyoto
    • Kyoto-shi, Kyoto, Japan, 602-8566
      • Duplicate_Kyoto Prefectural University of Medicine /ID# 167661
  • Miyagi
    • Sendai-shi, Miyagi, Japan, 9808574
      • Tohoku University Hospital /ID# 169259
  • Nagasaki
    • Nagasaki-shi, Nagasaki, Japan, 852-8501
      • Nagasaki University Hospital /ID# 168632
  • Okayama
    • Okayama-shi, Okayama, Japan, 700-8558
      • Okayama University Hospital /ID# 204124
  • Osaka
    • Osaka-sayama-shi, Osaka, Japan, 589-8511
      • Duplicate_Kindai University Hospital /ID# 167662
    • Osaka-shi, Osaka, Japan, 545-8586
      • Osaka Metropolitan University Hospital /ID# 169055
  • Saitama
    • Hidaka-shi, Saitama, Japan, 350-1298
      • Saitama Medical University International Medical Center /ID# 167814
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8431
      • Juntendo University Hospital /ID# 168309
    • Bunkyo-ku, Tokyo, Japan, 113-8677
      • Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital /ID# 168639
    • Komae-shi, Tokyo, Japan, 201-8601
      • The Jikei University Daisan Hospital /ID# 168745
    • Shinagawa-ku, Tokyo, Japan, 141-8625
      • NTT Medical Center Tokyo /ID# 167975
  • Yamagata
    • Yamagata-shi, Yamagata, Japan, 990-9585
      • Yamagata University Hospital /ID# 167634
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital /ID# 153675
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center /ID# 153674
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 05030
      • Duplicate_Konkuk University Medical Ctr /ID# 153973
• Norway
  • Gralum, Norway, 1714
    • Sykehuset Ostfold Kalnes /ID# 157755
  • Akershus
    • Nordlenangen, Akershus, Norway, 1474
      • Akershus universitetssykehus /ID# 154279
  • Buskerud
    • Drammen, Buskerud, Norway, 3004
      • Drammen Sykehus /ID# 154280
  • Hordaland
    • Bergen, Hordaland, Norway, 5021
      • Haukeland University Hospital /ID# 154281
• Poland
  • Dolnoslaskie
    • Wroclaw, Dolnoslaskie, Poland, 50-556
      • Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu /ID# 153389
  • Malopolskie
    • Krakow, Malopolskie, Poland, 31-826
      • Osrodek Badan Klinicznych przy Szpitalu Specjalistycznym im. Ludwika Rydygiera w /ID# 169846
  • Slaskie
    • Chorzow, Slaskie, Poland, 41-500
      • SP ZOZ Zespol Szpitali Miejskich w Chorzowie /ID# 153385
• Portugal
  • Braga, Portugal, 4710-423
    • Duplicate_Hospital de Braga /ID# 154797
  • Porto, Portugal, 4200-072
    • IPO Porto FG, EPE /ID# 154138
• Puerto Rico
  • San Juan, Puerto Rico, 00921-3201
    • VA Caribbean Healthcare System /ID# 160507
• Russian Federation
  • Moscow, Russian Federation, 125167
    • Federal State Budgetary Ins NRC for Hematology of MoH of Russian Federation /ID# 155740
  • Samara, Russian Federation, 443099
    • Samara State Medical University /ID# 157462
  • Kemerovskaya Oblast
    • Kemerovo, Kemerovskaya Oblast, Russian Federation, 650099
      • Kuzbass Regional Clinical Hospital /ID# 157461
  • Moskva
    • Moscow, Moskva, Russian Federation, 125284
      • Moscow State budget healthcare /ID# 155738
  • Nizhegorodskaya Oblast
    • Nizhniy Novgorod, Nizhegorodskaya Oblast, Russian Federation, 603126
      • Nizhny Novgorod Regional Clinical Hospital named N.A. Semashko /ID# 153268
  • Penzenskaya Oblast
    • Penza, Penzenskaya Oblast, Russian Federation, 440071
      • Duplicate_Regional Oncology Dispensary /ID# 153264
  • Ryazanskaya Oblast
    • Ryazan, Ryazanskaya Oblast, Russian Federation, 390039
      • State Institution of Health of the Ryazan Regional Clinical Hospital /ID# 157460
  • Saratovskaya Oblast
    • Saratov, Saratovskaya Oblast, Russian Federation, 410012
      • Saratov State Medical University n.a. V.I. Razumovskiy /ID# 153267
• South Africa
  • Gauteng
    • Pretoria, Gauteng, South Africa, 0001
      • University of Pretoria /ID# 153682
    • Pretoria, Gauteng, South Africa, 0044
      • Albert Alberts Stem Cell Transplant Centre /ID# 153684
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona /ID# 153255
  • Barcelona, Spain, 08041
    • Hospital Santa Creu i Sant Pau /ID# 153193
  • Madrid, Spain, 28006
    • Hospital Universitario de la Princesa /ID# 153256
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Maranon /ID# 153260
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre /ID# 153258
  • Malaga, Spain, 29010
    • Hospital Universitario Virgen de la Victoria /ID# 153257
  • Valencia, Spain, 46026
    • Hospital Universitario y Politecnico La Fe /ID# 153259
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Hospital Universitario de Navarra /ID# 153254
• Sweden
  • Lund, Sweden, 221 85
    • Dup_VO Hematologi /ID# 153174
  • Stockholm, Sweden, 171 76
    • Karolinska University Hospital /ID# 170003
  • Uppsala Lan
    • Uppsala, Uppsala Lan, Sweden, 751 85
      • Akademiska Sjukhuset /ID# 153034
  • Vastra Gotalands Lan
    • Uddevalla, Vastra Gotalands Lan, Sweden, 451 80
      • Uddevalla sjukhus /ID# 156875
• Taiwan
  • Kaohsiung, Taiwan, 807
    • Kaohsiung Medical University Chung-Ho Memorial Hospital /ID# 153902
  • Taichung City, Taiwan, 40447
    • China Medical University Hospital /ID# 153904
  • Taipei City, Taiwan, 100
    • National Taiwan University Hospital /ID# 153900
  • Changhua County
    • Changhua city, Changhua County, Taiwan, 50006
      • Changhua Christian Hospital /ID# 153899
• Turkey
  • Ankara, Turkey, 06100
    • Hacettepe University Faculty of Medicine /ID# 202073
  • Ankara, Turkey, 06620
    • Ankara Universitesi Fakultesi /ID# 155200
  • Samsun, Turkey, 55139
    • Ondokuz Mayis Universitesi Tip /ID# 155201
• Ukraine
  • Dnipro, Ukraine, 49102
    • Municipal Non-Profit Enterprise City Clinical Hospital 4 of Dnipro City Council /ID# 153511
  • Kyiv, Ukraine, 04107
    • Kyiv Regional Onco Dispensary /ID# 153514
  • Poltava, Ukraine, 36011
    • Poltava Reg Clin Hosp Sklifoso /ID# 153513
  • Vinnytska Oblast
    • Kiev, Vinnytska Oblast, Ukraine, 04112
      • Kyiv city clinical hospital #9 /ID# 153510
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope /ID# 154105
    • Los Angeles, California, United States, 90095
      • University of California, Los Angeles /ID# 154107
    • Sacramento, California, United States, 95817
      • University of California, Davis Comprehensive Cancer Center /ID# 162725
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory Midtown Infectious Disease Clinic /ID# 162534
  • Illinois
    • Chicago, Illinois, United States, 60611-2927
      • Northwestern University Feinberg School of Medicine /ID# 201133
    • Chicago, Illinois, United States, 60637-1426
      • University of Chicago Medicine /ID# 154108
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Fort Wayne Medical Oncology /ID# 157190
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Cotton-O'Neil Clinical Res Ctr /ID# 155136
  • Kentucky
    • Louisville, Kentucky, United States, 40202-3700
      • Norton Cancer Institute /ID# 154992
  • Maine
    • Brewer, Maine, United States, 04412
      • EMMC Cancer Care /ID# 154991
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University /ID# 154104
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital /ID# 200752
    • Boston, Massachusetts, United States, 02215-5400
      • Beth Israel Deaconess Medical Center /ID# 201155
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute /ID# 167009
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Sepctrum Health Medical Center /ID# 159522
  • New York
    • New York, New York, United States, 10032-3725
      • Columbia Univ Medical Center /ID# 154101
    • New York, New York, United States, 10065-6007
      • Memorial Sloan Kettering Cancer Center-Koch Center /ID# 165077
  • North Carolina
    • Durham, North Carolina, United States, 27710-3000
      • Duke Cancer Center /ID# 154106
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15260
      • University of Pittsburgh MC /ID# 154102
  • Tennessee
    • Nashville, Tennessee, United States, 37203-1632
      • Tennessee Oncology-Nashville Centennial /ID# 200854
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center /ID# 154100
    • Temple, Texas, United States, 76508-0001
      • Baylor Scott & White Medical Center- Temple /ID# 157191
  • Utah
    • Salt Lake City, Utah, United States, 84112-5500
      • University of Utah /ID# 157192
  • Vermont
    • Burlington, Vermont, United States, 05405
      • University Of Vermont Medical /ID# 157196

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant must have confirmation of Acute Myeloid Leukemia (AML) by World Health Organization (WHO) criteria, previously untreated and be ineligible for treatment with a standard cytarabine and anthracycline induction regimen due age or comorbidities.
• Participant must be >= 18 years of age.
• Participant must have a projected life expectancy of at least 12 weeks.

• Participant must be considered ineligible for induction therapy defined by the following:

  a. >= 75 years of age; or b. >= 18 to 74 years of age with at least one of the following comorbidities: i. Eastern Cooperative Oncology Group (ECOG) Performance Status of 2 or 3; ii. Cardiac history of Congestive Heart Failure (CHF) requiring treatment or Ejection Fraction <= 50% or chronic stable angina; iii. Diffusing capacity of the Lung for Carbon Monoxide (DLCO) <= 65% or Forced Expiratory Volume in 1 second (FEV1) <= 65%; iv. Creatinine clearance >= 30 mL/min to < 45 ml/min; v. Moderate hepatic impairment with total bilirubin > 1.5 to <= 3.0 × Upper Limit of Normal (ULN); vi. Any other comorbidity that the physician judges to be incompatible with intensive chemotherapy must be reviewed and approved by the AbbVie Therapeutic Medical Director during screening and before study enrollment.

• Participant must have an ECOG Performance status:

  1. 0 to 2 for Participants >= 75 years of age or
  2. 0 to 3 for Participants >= 18 to 74 years of age.
• Participant must have adequate renal function as demonstrated by a creatinine >= 30 mL/min; calculated by the Cockcroft Gault formula or measured by 24 hours urine collection.

• Participant must have adequate liver function as demonstrated by:

  1. aspartate aminotransferase (AST) <= 3.0 x ULN*
  2. alanine aminotransferase (ALT) <= 3.0 x ULN*
  3. bilirubin <= 1.5 x ULN* * Unless considered to be due to leukemic organ involvement

  i. Participants who are < 75 years of age may have a bilirubin of <= 3.0 x ULN

• Female participants must be either postmenopausal defined as:

  1. Age > 55 years with no menses for 12 or more months without an alternative medical cause.
  2. Age ≤ 55 years with no menses for 12 or more months without an alternative medical cause AND an follicle stimulating hormone (FSH) level >40 international units per liter (IU/L); or
  3. Permanently surgical sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy); or
  4. Women of Childbearing Potential (WOCBP) practicing at least one protocol specified method of birth control, starting at Study Day 1 through at least 90 days after the last dose of study drug.
• Male participants who are sexually active, must agree, from Study Day 1 through at least 90 days after the last dose of study drug, to practice the protocol specified contraception. Male subjects must agree to refrain from sperm donation from initial study drug administration through at least 90 days after the last dose of study drug.

• Female participants of childbearing potential must have negative results for pregnancy test performed:

  1. At Screening with a serum sample obtained within 14 days prior to the first study drug administration, and
  2. Prior to dosing with urine sample obtained on Cycle 1 Day 1, if it has been > 7 days since obtaining the serum pregnancy test results.
• Participant must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures.

Exclusion Criteria:

• Participant has received treatment with the following:

  1. A hypomethylating agent, venetoclax and/or chemo therapeutic agent for Myelodysplastic syndrome (MDS).
  2. Chimeric Antigen Receptor (CAR)-T cell therapy.
  3. Experimental therapies for MDS or Acute Myeloid Leukemia (AML).
  4. Current participation in another research or observational study.
• Participant has history of myeloproliferative neoplasm (MPN) including myelofibrosis, essential thrombocythemia, polycythemia vera, chronic myeloid leukemia (CML) with or without BCR-ABL1 translocation and AML with BCR-ABL1 translocation.

• Participant has the following:

  a. Favorable risk cytogenetics such as t(8;21), inv(16) or t(16;16) or t(15;17) as per the National Comprehensive Cancer Network (NCCN) Guidelines Version 2, 2016 for Acute Myeloid Leukemia.

• Participant has acute promyelocytic leukemia
• Participant has known active central nervous system (CNS) involvement with AML.
• Participant has known human immunodeficiency virus (HIV) infection (due to potential drug-drug interactions between antiretroviral medications and venetoclax) HIV testing will be performed at Screening, only if required per local guidelines or institutional standards.
• Participant is known to be positive for hepatitis B or C infection [HCV Ab indicative of a previous or current infection; and/or positive HBs Ag or detected sensitivity on hepatitis B virus (HBV) deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) test for HBc Ab and/or HBs Ab positivity] with the exception of those with an undetectable viral load within 3 months screening. Hepatitis B or C testing is not required.
• Participant has received strong and/or moderate CYP3A inducers within 7 days prior to the initiation of study treatment; additional details as described in the protocol.
• Participant has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Starfruit within 3 days prior to the initiation of study treatment.
• Participant has a cardiovascular disability status of New York Heart Association Class > 2. Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea, or anginal pain.
• Participant has chronic respiratory disease that requires continuous oxygen, or significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, any other medical condition or known hypersensitivity to any of the study medications including excipients of azacitidine that in the opinion of the investigator would adversely affect his/her participating in this study.
• Participant has a malabsorption syndrome or other condition that precludes enteral route of administration.
• Participant exhibits evidence of other clinically significant uncontrolled systemic infection requiring therapy (viral, bacterial or fungal).

• Participant has a history of other malignancies within 2 years prior to study entry, with the exception of:

  1. Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast;
  2. Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin;
  3. Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent; requires discussion with TA MD.
• Participant has a white blood cell count > 25 × 10^9/L. (Hydroxyurea or leukapheresis are permitted to meet this criterion.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Group 1 and Group 2: Placebo + Azacitidine 75 mg/m^2; Participants enrolled under original protocol and enrolled during or after protocol amendment 1 received venetoclax-matching placebo, orally, every day (QD), from Day 1 to Day 28 of each 28 day cycle along with azacitidine 75 mg/m^2, subcutaneously (SC) or intravenously (IV), QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).	Drug: Placebo; Matching placebo tablet; Drug: Azacitidine; Solution for subcutaneous or intravenous administration.
Active Comparator: Group 1 and Group 2: Venetoclax 100 mg/200 mg/400 mg + Azacitidine 75 mg/m^2; Participants enrolled under original protocol and enrolled during or after protocol amendment 1 received venetoclax 100 mg, once orally, on Day 1 of Cycle 1 followed by venetoclax 200 mg, once orally, on Day 2 of Cycle 1 and venetoclax 400 mg, orally, QD, on Day 3 to Day 28 of each 28 day cycle along with azacitidine 75 mg/m^2, SC or IV, QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).	Drug: Venetoclax; Tablet; Other Names: ABT-199; Drug: Azacitidine; Solution for subcutaneous or intravenous administration.
Active Comparator: Open Label China Cohort: Venetoclax 400 mg + Azacitidine 75 mg/m^2; Participants received venetoclax 400 mg, orally, QD, from Day 1 to Day 28 of each 28 day cycle along with azacitidine 75 mg/m^2, SC, QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).	Drug: Venetoclax; Tablet; Other Names: ABT-199; Drug: Azacitidine; Solution for subcutaneous or intravenous administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS is defined as the number of days from the date of randomization to the date of death. Log rank test was used to compare the OS distribution between two treatment arms. Cox regression was used to report the hazard ratio.	From the study start up to death or alive or lost to follow-up (up to approximately 4.8 years; data cut off date: 1 December 2021)
Percentage of Participants With Complete Remission (CR) and Complete Remission With Incomplete Marrow Recovery (CRi)	CR and CRi was calculated based on current International Working Group (IWG) criteria. CR is defined as absolute neutrophil count >10^3/ microliter (mcL), platelets >10^5/mcL, red cell transfusion independence, and bone marrow with <5% blasts. CRi is defined as bone marrow with less than 5% blasts, and absolute neutrophils of ≤10^3/mcL or platelets ≤10^5/mcL. Percentages are rounded off to whole number at the nearest decimal.	From the study start up to death (up to approximately 4.8 years; data cut-off date: 1 December 2021)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-free Survival (EFS)	EFS will be defined as the number of days from randomization to the date of progressive disease, relapse from CR or CRi, treatment failure or death from any cause.	Measured up to 2 years after the last participant is randomized
Global Health Status/Quality of Life (GHS/QoL)	Improvement in GHS/QoL will be assessed using the Patient Reported Outcomes Measurement Information System (PROMIS) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30).	Measured at participant's Day 1 of Cycle 1 (each cycle is 28 days) and at Day 1 of every Cycle thereafter for up to 2 years following the last subject last visit
Percentage of Participants Achieving Composite Complete Remission (CR or CRi)	This will be calculated based on current International Working Group (IWG) criteria. CR is defined as absolute neutrophil count > 10^3/mcL, platelets > 10^5/mcL, red cell transfusion independence, and bone marrow with < 5% blasts. CRi is defined as bone marrow with less than 5% blasts, and absolute neutrophils of <= 10^3/mcL or platelets <= 10^5/mcL.	Up to 6 months after the first 225 participants are randomized
Complete Remission or Complete Remission With Partial Hematologic Recovery Rate (CR+CRh)	A response of CRh is defined as Bone marrow with <5% blasts, peripheral blood neutrophil count >0.5*10^3/mcL and peripheral blood platelet count >0.5*10^5/mcL.	Measured up to 2 years after the last participant is randomized
Post Baseline Transfusion Independence Rate	Transfusion Independence is defined as a period of 56 days with no transfusion between first dose of study drug and the last dose of study drug + 30 days. The rate of conversion for red blood cells (RBC) and platelets is defined as percentage of participants being post-baseline transfusion independent from baseline transfusion dependence.	Measured up to 2 years after the last participant is randomized
Complete Remission (CR) Rate	The percentage of participants with complete remission (CR) will be calculated based on the modified IWG criteria for AML.	Measured up to 2 years after the last participant is randomized
Fatigue/Quality of Life (QoL)	Fatigue QoL will be assessed using the Patient Reported Outcomes Measurement Information System (PROMIS) Cancer Fatigue Short Form (SF) 7a global fatigue score	Measured at participant's Day 1 of Cycle 1 (each cycle is 28 days) and at Day 1 of every Cycle thereafter for up to 2 years following the last participant last visit

Collaborators and Investigators

• Sponsor: AbbVie
• Collaborators: Genentech, Inc.
• Investigators: Study Director: ABBVIE INC., AbbVie

Publications and helpful links

General Publications

• Badawi M, Chen X, Marroum P, Suleiman AA, Mensing S, Koenigsdorfer A, Schiele JT, Palenski T, Samineni D, Hoffman D, Menon R, Salem AH. Bioavailability Evaluation of Venetoclax Lower-Strength Tablets and Oral Powder Formulations to Establish Interchangeability with the 100 mg Tablet. Clin Drug Investig. 2022 Aug;42(8):657-668. doi: 10.1007/s40261-022-01172-4. Epub 2022 Jul 13.
• Pratz KW, Chai X, Xie J, Yin L, Nie X, Montez M, Iantuono E, Downs L, Ma E. Cost-Effectiveness Analysis of Venetoclax in Combination with Azacitidine Versus Azacitidine Monotherapy in Patients with Acute Myeloid Leukemia Who are Ineligible for Intensive Chemotherapy: From a US Third Party Payer Perspective. Pharmacoeconomics. 2022 Aug;40(8):777-790. doi: 10.1007/s40273-022-01145-7. Epub 2022 Jun 13.
• Konopleva M, Thirman MJ, Pratz KW, Garcia JS, Recher C, Pullarkat V, Kantarjian HM, DiNardo CD, Dail M, Duan Y, Chyla B, Potluri J, Miller CL, Wei AH. Impact of FLT3 Mutation on Outcomes after Venetoclax and Azacitidine for Patients with Treatment-Naive Acute Myeloid Leukemia. Clin Cancer Res. 2022 Jul 1;28(13):2744-2752. doi: 10.1158/1078-0432.CCR-21-3405.
• Pollyea DA, DiNardo CD, Arellano ML, Pigneux A, Fiedler W, Konopleva M, Rizzieri DA, Smith BD, Shinagawa A, Lemoli RM, Dail M, Duan Y, Chyla B, Potluri J, Miller CL, Kantarjian HM. Impact of Venetoclax and Azacitidine in Treatment-Naive Patients with Acute Myeloid Leukemia and IDH1/2 Mutations. Clin Cancer Res. 2022 Jul 1;28(13):2753-2761. doi: 10.1158/1078-0432.CCR-21-3467.
• Pratz KW, Jonas BA, Pullarkat V, Recher C, Schuh AC, Thirman MJ, Garcia JS, DiNardo CD, Vorobyev V, Fracchiolla NS, Yeh SP, Jang JH, Ozcan M, Yamamoto K, Illes A, Zhou Y, Dail M, Chyla B, Potluri J, Dohner H. Measurable Residual Disease Response and Prognosis in Treatment-Naive Acute Myeloid Leukemia With Venetoclax and Azacitidine. J Clin Oncol. 2022 Mar 10;40(8):855-865. doi: 10.1200/JCO.21.01546. Epub 2021 Dec 15.
• DiNardo CD, Jonas BA, Pullarkat V, Thirman MJ, Garcia JS, Wei AH, Konopleva M, Dohner H, Letai A, Fenaux P, Koller E, Havelange V, Leber B, Esteve J, Wang J, Pejsa V, Hajek R, Porkka K, Illes A, Lavie D, Lemoli RM, Yamamoto K, Yoon SS, Jang JH, Yeh SP, Turgut M, Hong WJ, Zhou Y, Potluri J, Pratz KW. Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia. N Engl J Med. 2020 Aug 13;383(7):617-629. doi: 10.1056/NEJMoa2012971.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2017
• Primary Completion (Actual): December 1, 2021
• Study Completion (Estimated): September 25, 2024

Study Registration Dates

• First Submitted: December 13, 2016
• First Submitted That Met QC Criteria: December 13, 2016
• First Posted (Estimated): December 15, 2016

Study Record Updates

• Last Update Posted (Actual): July 3, 2023
• Last Update Submitted That Met QC Criteria: June 27, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Acute Myeloid Leukemia; Venetoclax; Azacitidine; Treatment Naïve
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Venetoclax; Azacitidine
• Other Study ID Numbers: M15-656; 2016-001466-28 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• IPD Sharing Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• IPD Sharing Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous independent scientific research, and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No