Acute Myeloid Leukemia (AML)Phase 3Viale-aNCT02993523
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
A Phase 3 study testing Azacitidine and Venetoclax in people with Acute Myeloid Leukemia (AML), run by AbbVie at 172 sites in 29 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia (AML)
- What is being tested?
- Azacitidine and Venetoclax
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 443 participants
- Where
- 172 sitesin 29 countries
- Study dates
- 2 Feb 2017to 15 Jun 2026
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- >= 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:
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- 0 to 2 for Participants >= 75 years of age or
- 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:
- aspartate aminotransferase (AST) <= 3.0 x ULN*
- alanine aminotransferase (ALT) <= 3.0 x ULN*
- bilirubin <= 1.5 x ULN* * Unless considered to be due to leukemic organ involvement
- Participants who are < 75 years of age may have a bilirubin of <= 3.0 x ULN
- Female participants must be either postmenopausal defined as:
- Age > 55 years with no menses for 12 or more months without an alternative medical cause.
- 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
- Permanently surgical sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy); or
- 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:
- At Screening with a serum sample obtained within 14 days prior to the first study drug administration, and
- 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.
Who cannot join
- Participant has received treatment with the following:
- A hypomethylating agent, venetoclax and/or chemo therapeutic agent for Myelodysplastic syndrome (MDS).
- Chimeric Antigen Receptor (CAR)-T cell therapy.
- Experimental therapies for MDS or Acute Myeloid Leukemia (AML).
- 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.
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- Participant has the following:
- 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:
- Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast;
- Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin;
- 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.)
Trial locations and contacts
172 sites in 29 countries.
172 sites in 29 countries
United States24 sites
Emory Midtown Infectious Disease Clinic /ID# 162534
Atlanta, Georgia, 30322
Johns Hopkins University /ID# 154104
Baltimore, Maryland, 21287
Massachusetts General Hospital /ID# 200752
Boston, Massachusetts, 02114
Beth Israel Deaconess Medical Center /ID# 201155
Boston, Massachusetts, 02215-5400
Dana-Farber Cancer Institute /ID# 167009
Boston, Massachusetts, 02215
EMMC Cancer Care /ID# 154991
Brewer, Maine, 04412
University Of Vermont Medical /ID# 157196
Burlington, Vermont, 05405
Northwestern University Feinberg School of Medicine /ID# 201133
Chicago, Illinois, 60611-2927
University of Chicago Medicine /ID# 154108
Chicago, Illinois, 60637-1426
City of Hope /ID# 154105
Duarte, California, 91010
Duke Cancer Center /ID# 154106
Durham, North Carolina, 27710-3000
Fort Wayne Medical Oncology /ID# 157190
Fort Wayne, Indiana, 46804
Sepctrum Health Medical Center /ID# 159522
Grand Rapids, Michigan, 49503
University of Texas MD Anderson Cancer Center /ID# 154100
Houston, Texas, 77030
University of California, Los Angeles /ID# 154107
Los Angeles, California, 90095
Norton Cancer Institute /ID# 154992
Louisville, Kentucky, 40202-3700
Tennessee Oncology-Nashville Centennial /ID# 200854
Nashville, Tennessee, 37203-1632
Columbia Univ Medical Center /ID# 154101
New York, New York, 10032-3725
Memorial Sloan Kettering Cancer Center-Koch Center /ID# 165077
New York, New York, 10065-6007
University of Pittsburgh MC /ID# 154102
Pittsburgh, Pennsylvania, 15260
University of California, Davis Comprehensive Cancer Center /ID# 162725
Sacramento, California, 95817
University of Utah /ID# 157192
Salt Lake City, Utah, 84112-5500
Baylor Scott & White Medical Center- Temple /ID# 157191
Temple, Texas, 76508-0001
Cotton-O'Neil Clinical Res Ctr /ID# 155136
Topeka, Kansas, 66606
Japan19 sites
Juntendo University Hospital /ID# 168309
Bunkyo-ku, Tokyo, 113-8431
Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital /ID# 168639
Bunkyo-ku, Tokyo, 113-8677
National Hospital Organization Kyushu Cancer Center /ID# 201111
Fukuoka, Fukuoka, 811-1395
Kyushu University Hospital /ID# 169095
Fukuoka, Fukuoka, 812-8582
Saitama Medical University International Medical Center /ID# 167814
Hidaka-shi, Saitama, 350-1298
National Hospital Organization Mito Medical Center /ID# 168219
Higashi, Ibaraki, 311-3193
Hitachi General Hospital /ID# 201109
Hitachi-shi, Ibaraki, 317-0077
The Jikei University Daisan Hospital /ID# 168745
Komae-shi, Tokyo, 201-8601
Duplicate_Kyoto Prefectural University of Medicine /ID# 167661
Kyoto, Kyoto, 602-8566
Gunmaken Saiseikai Maebashi Hospital /ID# 168316
Maebashi, Gunma, 371-0821
Nagasaki University Hospital /ID# 168632
Nagasaki, Nagasaki, 852-8501
Aichi Cancer Center Hospital /ID# 200824
Nagoya, Aichi-ken, 464-8681
Okayama University Hospital /ID# 204124
Okayama, Okayama-ken, 700-8558
Osaka Metropolitan University Hospital /ID# 169055
Osaka, Osaka, 545-8586
Duplicate_Kindai University Hospital /ID# 167662
Osaka-sayama-shi, Osaka, 589-8511
Tohoku University Hospital /ID# 169259
Sendai, Miyagi, 9808574
NTT Medical Center Tokyo /ID# 167975
Shinagawa-ku, Tokyo, 141-8625
Yamagata University Hospital /ID# 167634
Yamagata, Yamagata, 990-9585
University of Fukui Hospital /ID# 167432
Yoshida-gun, Fukui, 910-1193
China13 sites
The First Hospital of Jilin University /ID# 167490
Changchun, Jilin, 130021
West China Hospital, Sichuan University /ID# 167492
Chengdu, Sichuan, 610041
Fujian Medical University Union Hospital /ID# 167314
Fuzhou, Fujian, 350001
Nanfang Hospital of Southern Medical University /ID# 170148
Guangzhou, Guangdong, 510515
The First Affiliated Hospital, Zhejiang University School of Medicine /ID# 167317
Hangzhou, Zhejiang, 310006
Qilu Hospital of Shandong University /ID# 167485
Jinan, 250012
Jiangsu Province Hospital /ID# 167489
Nanjing, Jiangsu, 210029
Ruijin Hospital, Shanghai Jiaotong University School of Medicine /ID# 167318
Shanghai, Shanghai Municipality, 200065
The Second Hospital of Hebei Medical University /ID# 167316
Shijiazhuang, Hebei, 050000
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sc /ID# 167487
Tianjin, Tianjin Municipality, 300020
Tongji Hospital Tongji Medical College Huazhong University of Science and Techno /ID# 167315
Wuhan, Hubei, 430022
Union Hospital Tongji Medical College Huazhong University of Science and Technol /ID# 167493
Wuhan, Hubei, 430022
Henan Cancer Hospital /ID# 167320
Zhengzhou, Henan, 450008
Italy10 sites
Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona /ID# 171220
Ancona, 60126
Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni /ID# 152875
Bergamo, 24127
IRCCS Azienda Ospedaliero-Universitaria di Bologna /ID# 152883
Bologna, 40138
Ospedale Policlinico San Martino /ID# 158104
Genova, 16132
Presidio Ospedaliero Vito Fazzi /ID# 170837
Lecce, Apulia, 73100
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico /ID# 152882
Milan, 20122
Azienda Ospedaliera di Rilievo Nazionale Antonio Cardarelli /ID# 152879
Naples, 80131
Grande Ospedale Metropolitano Bianchi Melacrino Morelli /ID# 152877
Reggio Calabria, 89124
Fondazione PTV Policlinico Tor Vergata /ID# 152881
Rome, Roma, 00133
Azienda Ospedaliero-Universitaria Sant'Andrea /ID# 152876
Rome, 00189
Russia8 sites
Kuzbass Regional Clinical Hospital /ID# 157461
Kemerovo, Kemerovo Oblast, 650099
Moscow State budget healthcare /ID# 155738
Moscow, Moscow, 125284
Federal State Budgetary Ins NRC for Hematology of MoH of Russian Federation /ID# 155740
Moscow, 125167
Nizhny Novgorod Regional Clinical Hospital named N.A. Semashko /ID# 153268
Nizhny Novgorod, Nizhny Novgorod Oblast, 603126
Duplicate_Regional Oncology Dispensary /ID# 153264
Penza, Penza Oblast, 440071
State Institution of Health of the Ryazan Regional Clinical Hospital /ID# 157460
Ryazan, Ryazan Oblast, 390039
Samara State Medical University /ID# 157462
Samara, 443099
Saratov State Medical University n.a. V.I. Razumovskiy /ID# 153267
Saratov, Saratov Oblast, 410012
Spain8 sites
Hospital Clinic de Barcelona /ID# 153255
Barcelona, 08036
Hospital Santa Creu i Sant Pau /ID# 153193
Barcelona, 08041
Hospital Universitario de la Princesa /ID# 153256
Madrid, 28006
Hospital General Universitario Gregorio Maranon /ID# 153260
Madrid, 28007
Hospital Universitario 12 de Octubre /ID# 153258
Madrid, 28041
Hospital Universitario Virgen de la Victoria /ID# 153257
Málaga, 29010
Hospital Universitario de Navarra /ID# 153254
Pamplona, Navarre, 31008
Hospital Universitario y Politecnico La Fe /ID# 153259
Valencia, 46026
Australia7 sites
Royal Adelaide Hospital /ID# 154271
Adelaide, South Australia, 5000
Alfred Health /ID# 154275
Melbourne, Victoria, 3004
St Vincent's Hospital Melbourne /ID# 155094
Melbourne, Victoria, 3065
Sir Charles Gairdner Hospital /ID# 163924
Nedlands, Western Australia, 6009
The Royal Melbourne Hospital /ID# 155095
Parkville, Victoria, 3050
Royal Perth Hospital /ID# 154274
Perth, Western Australia, 6000
Princess Alexandra Hospital /ID# 154272
Woolloongabba, Queensland, 4102
Hungary7 sites
Semmelweis Egyetem /ID# 153816
Budapest, 1085
Duplicate_Semmelweis Egyetem /ID# 153815
Budapest, 1088
Del-pesti Centrumkorhaz Orszagos Hematologiai es Infektologiai Intezet /ID# 158990
Budapest, 1097
Debreceni Egyetem Klinikai Kozpont /ID# 153814
Debrecen, Hajdú-Bihar, 4032
Somogy Megyei Kaposi Mor Oktato Korhaz /ID# 153813
Kaposvár, Somogy County, 7400
Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz Josa Andras Okta /ID# 169854
Nyíregyháza, Nyiregyhaza, 4400
Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont /ID# 153812
Szeged, Csongrád megye, 6725
Austria6 sites
Medizinische Universitaet Graz /ID# 157882
Graz, Styria, 8036
Ordensklinikum Linz GmbH Barmherzige Schwestern /ID# 154888
Linz, Upper Austria, 4010
Ordensklinikum Linz GmbH Elisabethinen /ID# 154885
Linz, Upper Austria, 4010
Duplicate_Landeskrankenhaus Salzburg /ID# 169719
Salzburg, 5020
Universitaetsklinikum St. Poelten /ID# 167436
Sankt Pölten, Lower Austria, 3100
Hanusch Krankenhaus /ID# 155676
Vienna, 1140
Germany6 sites
Universitaetsklinikum Frankfurt /ID# 153060
Frankfurt am Main, Hesse, 60590
Universitaetsklinikum Halle (Saale) /ID# 153058
Halle, 06120
Universitaetsklinikum Hamburg-Eppendorf (UKE) /ID# 153056
Hamburg, 20246
Medizinische Hochschule Hannover /ID# 153055
Hanover, 30625
Universitaetsklinikum Muenster /ID# 153059
Münster, North Rhine-Westphalia, 48149
Universitaetsklinikum Ulm /ID# 153054
Ulm, Baden-Wurttemberg, 89081
Israel6 sites
Assaf Harofeh Medical Center /ID# 158063
Be’er Ya‘aqov, 70300
Rambam Health Care Campus /ID# 154174
Haifa, 3109601
Hadassah /ID# 154172
Jerusalem, 91120
Rabin Medical Center /ID# 154176
Petah Tikva, 4941492
The Chaim Sheba Medical Center /ID# 154173
Ramat Gan, Tel Aviv, 5265601
Tel Aviv Sourasky Medical Center /ID# 154175
Tel Aviv, Tel Aviv, 6423906
Canada5 sites
Tom Baker Cancer Centre /ID# 159645
Calgary, Alberta, T2N 4N2
Juravinski Cancer Centre /ID# 153650
Hamilton, Ontario, L8V 1C3
Ottawa Hospital Research Institute /ID# 153541
Ottawa, Ontario, K1H 8L6
Princess Margaret Cancer Centre /ID# 153651
Toronto, Ontario, M5G 2M9
St. Paul's Hospital /ID# 159644
Vancouver, British Columbia, V6Z 1Y6
Belgium4 sites
AZ Sint-Jan Brugge /ID# 154041
Bruges, 8000
UZ Gent /ID# 153392
Ghent, Oost-Vlaanderen, 9000
UZ Brussel /ID# 153393
Jette, Brussels Capital, 1090
UCL Saint-Luc /ID# 153391
Woluwe-Saint-Lambert, Brussels Capital, 1200
Brazil4 sites
Hospital de Clinicas de Porto Alegre /ID# 157779
Porto Alegre, Rio Grande do Sul, 90035-903
Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto - USP /ID# 153099
Ribeirão Preto, São Paulo, 14051-140
Instituto de Ensino e Pesquisa São Lucas /ID# 157778
São Paulo, São Paulo, 01236-030
Instituto do Câncer do Estado de São Paulo - ICESP /ID# 153095
São Paulo, São Paulo, 01246-000
Czechia4 sites
Fakultni Nemocnice Brno /ID# 154019
Brno, 625 00
Fakultni nemocnice Hradec Kralove /ID# 154021
Hradec Králové, 500 05
Fakultni nemocnice Ostrava /ID# 154017
Ostrava, 708 52
Fakultni nemocnice Plzen /ID# 154018
Pilsen, 305 99
France4 sites
Chu Angers /Id# 153792
Angers, 49933
AP-HP - Hopital Saint-Louis /ID# 153787
Paris, 75010
CHU Bordeaux - Hopital Haut Leveque /ID# 153789
Pessac, Gironde, 33604
IUCT Oncopole /ID# 153788
Toulouse, 31059
Norway4 sites
Haukeland University Hospital /ID# 154281
Bergen, Hordaland, 5021
Drammen Sykehus /ID# 154280
Drammen, Buskerud, 3004
Sykehuset Ostfold Kalnes /ID# 157755
Grålum, 1714
Akershus universitetssykehus /ID# 154279
Nordlenangen, Akershus, 1474
Sweden4 sites
Dup_VO Hematologi /ID# 153174
Lund, 221 85
Karolinska University Hospital /ID# 170003
Stockholm, 171 76
Uddevalla sjukhus /ID# 156875
Uddevalla, Västra Götaland County, 451 80
Akademiska Sjukhuset /ID# 153034
Uppsala, Uppsala County, 751 85
Taiwan4 sites
Changhua Christian Hospital /ID# 153899
Changhua, Changhua County, 50006
Kaohsiung Medical University Chung-Ho Memorial Hospital /ID# 153902
Kaohsiung City, 807
China Medical University Hospital /ID# 153904
Taichung, 40447
National Taiwan University Hospital /ID# 153900
Taipei, 100
Ukraine4 sites
Municipal Non-Profit Enterprise City Clinical Hospital 4 of Dnipro City Council /ID# 153511
Dnipro, 49102
Kyiv city clinical hospital #9 /ID# 153510
Kiev, Vinnytsia Oblast, 04112
Kyiv Regional Onco Dispensary /ID# 153514
Kyiv, 04107
Poltava Reg Clin Hosp Sklifoso /ID# 153513
Poltava, 36011
Croatia3 sites
Duplicate_Klinicki bolnicki centar Osijek /ID# 153623
Osijek, County of Osijek-Baranja, 31000
Clinical Hospital Dubrava /ID# 153515
Zagreb, City of Zagreb, 10000
Klinicki bolnicki centar Zagreb /ID# 153383
Zagreb, City of Zagreb, 10000
Finland3 sites
Helsinki University Hospital /ID# 155223
Helsinki, Uusimaa, 00290
Tampere University Hospital /ID# 154963
Tampere, Pirkanmaa, 33520
Turku University Hospital /ID# 154964
Turku, 20520
Poland3 sites
SP ZOZ Zespol Szpitali Miejskich w Chorzowie /ID# 153385
Chorzów, Silesian Voivodeship, 41-500
Osrodek Badan Klinicznych przy Szpitalu Specjalistycznym im. Ludwika Rydygiera w /ID# 169846
Krakow, Lesser Poland Voivodeship, 31-826
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu /ID# 153389
Wroclaw, Lower Silesian Voivodeship, 50-556
South Korea3 sites
Duplicate_Konkuk University Medical Ctr /ID# 153973
Seoul, Seoul Teugbyeolsi, 05030
Seoul National University Hospital /ID# 153675
Seoul, 03080
Samsung Medical Center /ID# 153674
Seoul, 06351
Turkey (Türkiye)3 sites
Hacettepe University Faculty of Medicine /ID# 202073
Ankara, 06100
Ankara Universitesi Fakultesi /ID# 155200
Ankara, 06620
Ondokuz Mayis Universitesi Tip /ID# 155201
Samsun, 55139
Portugal2 sites
Duplicate_Hospital de Braga /ID# 154797
Braga, 4710-423
IPO Porto FG, EPE /ID# 154138
Porto, 4200-072
South Africa2 sites
University of Pretoria /ID# 153682
Pretoria, Gauteng, 0001
Albert Alberts Stem Cell Transplant Centre /ID# 153684
Pretoria, Gauteng, 0044
Denmark1 site
Aalborg University Hospital /ID# 154047
Aalborg, North Denmark, 9000
Puerto Rico1 site
VA Caribbean Healthcare System /ID# 160507
San Juan, 00921-3201
About this study
Official title: 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.
Read more
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.
- Conditions
- Acute Myeloid Leukemia (AML)
- Being tested
- Azacitidine, Venetoclax, Placebo
- Keywords
- Acute Myeloid Leukemia, Venetoclax, Treatment Naïve, Azacitidine
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzacitidineDrug
Solution for subcutaneous or intravenous administration.
VenetoclaxDrug
Also called ABT-199
Tablet
PlaceboDrug
Matching placebo tablet
| Study group | Role | What they receive |
|---|---|---|
| Group 1 and Group 2: Placebo + Azacitidine 75 mg/m^2 | Placebo comparator | 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). Receives: Drug: Azacitidine; Drug: Placebo |
| Group 1 and Group 2: Venetoclax 100 mg/200 mg/400 mg + Azacitidine 75 mg/m^2 | Active comparator | 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). Receives: Drug: Azacitidine; Drug: Venetoclax |
| Open Label China Cohort: Venetoclax 400 mg + Azacitidine 75 mg/m^2 | Active comparator | 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). Receives: Drug: Azacitidine; Drug: Venetoclax |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: From the study start up to death (up to approximately 4.8 years; data cut-off date: 1 December 2021)
Secondary outcomes (7)
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: 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: 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.
Measured: 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: 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: 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: 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: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2016 (estimated)
- Study start2 Feb 2017
- Primary completion1 Dec 2021
- Study completion15 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid Leukemia (AML)Studies of the same condition, open and under way.
- More trials run by AbbVieThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 443 participants (actual)
Sponsor and investigators
- Lead sponsor
- AbbVie
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- ABBVIE INC., Study director, AbbVie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02993523
- Sponsor's protocol ID
- M15-656
- Other IDs
- 2016-001466-28, 2016
- Acronym
- Viale-a
- Status last verified
- May 2026
- First submitted
- 13 Dec 2016
- Last updated
- 11 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
- Expanded access
- Available
Publications
Venditti A, Hou JZ, Fenaux P, Jonas BA, Vrhovac R, Montesinos P, Garcia JS, Rizzieri D, Thirman MJ, Zhang M, Potluri J, Miller C, Dhalla M, Pullarkat V. Outcomes of patients treated with venetoclax plus azacitidine versus azacitidine alone stratified by advanced age and acute myeloid leukemia composite model. Leukemia. 2025 Nov;39(11):2697-2707. doi: 10.1038/s41375-025-02730-3. Epub 2025 Sep 5.
PubMed 40913104Dohner H, Pratz KW, DiNardo CD, Wei AH, Jonas BA, Pullarkat VA, Thirman MJ, Recher C, Schuh AC, Babu S, Li X, Ku G, Liu Z, Sun Y, Potluri J, Dail M, Chyla B, Pollyea DA. Genetic risk stratification and outcomes among treatment-naive patients with AML treated with venetoclax and azacitidine. Blood. 2024 Nov 21;144(21):2211-2222. doi: 10.1182/blood.2024024944.
PubMed 39133921Pollyea DA, Pratz KW, Wei AH, Pullarkat V, Jonas BA, Recher C, Babu S, Schuh AC, Dail M, Sun Y, Potluri J, Chyla B, DiNardo CD. Outcomes in Patients with Poor-Risk Cytogenetics with or without TP53 Mutations Treated with Venetoclax and Azacitidine. Clin Cancer Res. 2022 Dec 15;28(24):5272-5279. doi: 10.1158/1078-0432.CCR-22-1183.
PubMed 36007102Badawi 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.
PubMed 35829925Pratz 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.
PubMed 35696071Konopleva 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.
PubMed 35063965Pollyea 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.
PubMed 35046058Pratz 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.
PubMed 34910556DiNardo 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.
PubMed 32786187