A Study of Venetoclax in Combination With Low Dose Cytarabine Versus Low Dose Cytarabine Alone in Treatment Naive Patients With Acute Myeloid Leukemia Who Are Ineligible for Intensive Chemotherapy

NCT ID: NCT03069352

Last Updated: 2025-09-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 211 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-05-23
• Study Completion Date: 2025-08-21

Brief Summary

The primary objective of this study is to evaluate if venetoclax when co administered with low-dose cytarabine (LDAC) improves overall survival (OS) versus LDAC and placebo, in treatment-naïve patients with acute myeloid leukemia (AML).

Detailed Description

Acute myeloid leukemia (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 patient has, and the age of the patient 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 cytarabine works better than cytarabine on its own.

This is a Phase 3, randomized, double-blind (treatment unknown to patients and doctors), placebo-controlled, multicenter study in patients with AML who are 18 or more years old and have not been treated before. Patients who take part in this study should not be suitable for intensive induction chemotherapy (usual starting treatment). Abbvie is funding this study which will take place at approximately 125 hospitals globally. In this study, 2/3 of patients will receive venetoclax every day with cytarabine and the remaining 1/3 will receive placebo (dummy) tablets with cytarabine.

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.

Conditions

Acute Myeloid Leukemia (AML)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Venetoclax + Low Dose Cytarabine (LDAC)

Venetoclax 600 mg orally every day (QD) plus LDAC 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.

Group Type: EXPERIMENTAL

Venetoclax

Intervention Type: DRUG

tablet

Cytarabine

Intervention Type: DRUG

Subcutaneous injection

Placebo + LDAC

Matching placebo to venetoclax orally QD plus LDAC 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

tablet

Cytarabine

Intervention Type: DRUG

Subcutaneous injection

Interventions

Placebo

tablet

Intervention Type: DRUG

Venetoclax

tablet

Intervention Type: DRUG

Cytarabine

Subcutaneous injection

Intervention Type: DRUG

Other Intervention Names

ABT-199; Venclexta; Cytosar-U; Ara-C; Arabinosylcytosine

Eligibility Criteria

Inclusion Criteria

1. Participant must have histological confirmation of acute myeloid leukemia (AML) by World Health Organization criteria, be ineligible for intensive induction chemotherapy and either be:

• ≥ 75 years of age OR
• ≥ 18 to 74 years of age and fulfill at least one criteria associated with lack of fitness for intensive induction chemotherapy:

• Eastern Cooperative Oncology Group (ECOG) performance status of 2 - 3
• Cardiac history of congestive heart failure (CHF) requiring treatment or ejection fraction ≤ 50% or chronic stable angina
• Diffusing capacity of the lung for carbon monoxide (DLCO) ≤ 65% or forced expiratory volume in 1 second (FEV1) ≤ 65%
• Creatinine clearance ≥ 30 mL/min to < 45 ml/min
• Moderate hepatic impairment with total bilirubin > 1.5 to ≤ 3.0 × upper limit of normal (ULN)
• Other comorbidity that the physician judges to be incompatible with conventional intensive chemotherapy which must be reviewed and approved by the study medical monitor before study enrollment

2. Participant must have an ECOG performance status:

• of 0 to 2 for subjects ≥ 75 years of age OR
• of 0 to 3 for subjects between 18 to 74 years of age

3. Participant must have a projected life expectancy of at least 12 weeks.

4. Participant must have adequate renal function as demonstrated by a creatinine clearance ≥ 30 mL/min; calculated by the Cockcroft Gault formula or measured by 24-hour urine collection.

5. Participant must have adequate liver function as demonstrated by:

• aspartate aminotransferase (AST) ≤ 3.0 × ULN*
• alanine aminotransferase (ALT) ≤ 3.0 × ULN*
• bilirubin ≤ 1.5 × ULN*

• Subjects who are < 75 years of age may have bilirubin of ≤ 3.0 × ULN

(*Unless considered to be due to leukemic organ involvement.)

6. 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 a follicle-stimulating hormone (FSH) level > 40 IU/L.

OR

• Permanently surgical sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).

OR

• A woman of childbearing potential (WOCBP) practicing at least one protocol specified method of birth control starting at Study Day 1 through at least 180 days after the last dose of study drug.

7. Male participants who are sexually active, must agree, from Study Day 1 through at least 180 days after the last dose of study drug, to practice protocol specified methods of contraception. Male subjects must agree to refrain from sperm donation from initial study drug administration through at least 180 days after the last dose of study drug.

8. Females 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.
• Subjects with borderline pregnancy tests at Screening must have a serum pregnancy test ≥ 3 days later to document continued lack of a positive result.

9. Participant must voluntarily sign and date an informed consent form, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures.

Exclusion Criteria

1. Participant has received any prior treatment for AML with the exception of hydroxyurea, allowed through the first cycle of study treatment. Note: Prior treatment for myelodysplastic syndrome is allowed except for use of cytarabine.

2. Participant had an antecedent myeloproliferative neoplasm (MPN) including myelofibrosis, essential thrombocytosis, polycythemia vera, or chronic myelogenous leukemia (CML) with or without BCR-ABL 1 translocation and AML with BCR-ABL 1 translocation.

3. Participants that have acute promyelocytic leukemia (APL).

4. Participant has known central nervous system (CNS) involvement with AML.

5. 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, if required per local guidelines or institutional standards.

6. Participant is known to be positive for hepatitis B virus (HBV), or hepatitis C virus (HCV) infection. Inactive hepatitis carrier status or low viral hepatitis titer on antivirals (non-exclusionary medications) are not excluded.

7. Participant has received strong or moderate cytochrome P450 3A4 (CYP3A) inducers 7 days prior to the initiation of study treatment.

• Chinese subjects are excluded from receiving strong and/or moderate CYP3A inhibitors 7 days prior to the initiation of study treatment through the end of intensive pharmacokinetic (PK) collection (24 hours post dose on Cycle 1 Day 10).

8. Participant has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or star fruit within 3 days prior to the initiation of study treatment.

9. Participant has cardiovascular disability status of New York Heart Association Class > 2. Class 2 is defined as cardiac disease which subjects are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea, or angina pain. Class 3 is defined as cardiac disease which subjects are comfortable at rest but less than ordinary activity causes fatigue, palpitation, or dyspnea. Class 4 is defined as cardiac disease which subjects have an inability to carry on any physical activity without discomfort, symptoms of heart failure at rest, and if any physical activity is undertaken then discomfort increases.

10. 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 LDAC that in the opinion of the investigator would adversely affect his/her participating in this study.

11. Participant has a malabsorption syndrome or other condition that precludes enteral route of administration.

12. Participant exhibits evidence of other clinically significant uncontrolled systemic infection requiring therapy (viral, bacterial or fungal).

13. Participant has a history of other malignancies 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.

14. Participant has a white blood cell count > 25 × 10^9/L. (Note: hydroxyurea administration or leukapheresis is permitted to meet this criterion).

15. Previous treatment with venetoclax and/or current participation in any other research study with investigational products.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

AbbVie Inc.

Role: STUDY_DIRECTOR

AbbVie

Locations

H. Lee Moffit Cancer Center /ID# 164273

Tampa, Florida, United States

Norton Cancer Institute /ID# 158998

Louisville, Kentucky, United States

Univ of Pittsburgh Med Ctr /ID# 158997

Pittsburgh, Pennsylvania, United States

Univ TX, MD Anderson /ID# 159678

Houston, Texas, United States

Swedish Medical Center /ID# 161280

Seattle, Washington, United States

Gundersen Health System /ID# 164272

La Crosse, Wisconsin, United States

Cemic /Id# 159676

Buenos Aires, , Argentina

Sanatorio Allende /ID# 159675

Córdoba, , Argentina

Calvary Mater Newcastle /ID# 160123

Waratah, New South Wales, Australia

Westmead Hospital /ID# 160121

Westmead, New South Wales, Australia

Alfred Hospital /ID# 160125

Melbourne, Victoria, Australia

Box Hill Hospital /ID# 162920

Melbourne, Victoria, Australia

Universitair Ziekenhuis Antwerpen /ID# 159566

Edegem, Antwerpen, Belgium

Cliniques Universitaires Saint Luc /ID# 159567

Woluwe-Saint-Lambert, Brussels Capital, Belgium

Centro de Pesquisas Oncologicas /ID# 163567

Florianópolis, Santa Catarina, Brazil

Hospital de Cancer de Barretos /ID# 163568

Barretos, São Paulo, Brazil

Hospital do Cancer Mae de Deus /ID# 163416

Porto Alegre, , Brazil

Casa de Saúde Santa Marcelina /ID# 163413

São Paulo, , Brazil

University of Alberta Hospital /ID# 159646

Edmonton, Alberta, Canada

CISSS de la Monteregie /ID# 159782

Greenfield Park, Quebec, Canada

Hospital Maisonneuve-Rosemont /ID# 159780

Montreal, Quebec, Canada

Hopital Sacre Coeur Montreal /ID# 160982

Montreal, Quebec, Canada

Fujian Medical Univ Union Hosp /ID# 167321

Fuzhou, Fujian, China

Nanfang Hospital of Southern Medical University /ID# 170147

Guangzhou, Guangdong, China

Jiangsu Province People's Hospital /ID# 167511

Nanjing, Jiangsu, China

The First Hosp of Jilin Univ /ID# 167512

Changchun, Jilin, China

Ruijin Hospital, Shanghai Jiaotong /ID# 167325

Shanghai, Shanghai Municipality, China

West China Hospital /ID# 167514

Chengdu, Sichuan, China

Blood disease hosp of Chinese Academy of Med Sciences(Institute of Hematology) /ID# 167509

Tianjin, Tianjin Municipality, China

The First Affiliated Hospital,College of Medicine, Zhejiang University /ID# 167324

Hangzhou, Zhejiang, China

Qilu Hospital of Shandong Univ /ID# 167507

Jinan, , China

Union Hospital Tongji Medical College Huazhong University of Science and Technol /ID# 167515

Wuhan, , China

Henan Cancer Hospital /ID# 167327

Zhengzhou, Henan, , China

Fakultni Nemocnice Brno /ID# 159247

Brno, , Czechia

Univ Hosp Ostrava-Poruba /ID# 159246

Ostrava, , Czechia

Fakult Nem Kralovske Vinohrady /ID# 159248

Prague, , Czechia

Centre Hospitalier Lyon Sud /ID# 159705

Pierre-Bénite, Rhone, France

Centre Hospitalier Le Mans /ID# 159702

Le Mans, Sarthe, France

Centre Hospitalier de la Cote /ID# 159697

Bayonne, , France

CHU Bordeaux /ID# 159704

Pessac, , France

CHU De Nancy /ID# 159700

Vandœuvre-lès-Nancy, , France

Schwarzwald-Baar-Klinikum /ID# 159571

Villingen-Schwenningen, Baden-Wurttemberg, Germany

Vivantes Klinikum Am Urban /ID# 159569

Berlin, , Germany

Universitaetsklinikum Hamburg /ID# 161760

Hamburg, , Germany

General Hospital of Athens Laiko /ID# 157870

Athens, Attica, Greece

Gen Univ Hosp Alexandroupolis /ID# 157868

Alexandroupoli, , Greece

General Hospital of Athens Evaggelismos and Ophthalmiatrio of Athens Polyclinic /ID# 157869

Athens, , Greece

University Gen Hosp of Patra /ID# 157871

Pátrai, , Greece

General Hospital of Thessaloniki George Papanikolaou /ID# 157867

Thessaloniki, , Greece

Dél-pesti Centrumkórház- Országos Hematológiai és Infektológiai Intézet /ID# 159127

Budapest IX, Budapest, Hungary

Pecsi Tudomanyegyetem /ID# 163161

Pécs, Pecs, Hungary

Semmelweis Egyetem I. Belklini /ID# 158180

Budapest, , Hungary

Debreceni Egyetem Klinikai Koz /ID# 158178

Debrecen, , Hungary

Petz Aladar Megyei Oktato Korh /ID# 161739

Győr, , Hungary

Kaposi Mor Oktato Korhaz /ID# 158175

Kaposvár, , Hungary

Bacs-Kiskun Megyei Korhaz /ID# 160973

Kecskemét, , Hungary

St. James's Hospital /ID# 162730

Dublin, Dublin, Ireland

Beaumont Hospital /ID# 162733

Dublin, , Ireland

University Hospital Galway /ID# 162734

Galway, , Ireland

University Hospital Limerick /ID# 162735

Limerick, , Ireland

University of Fukui Hospital /ID# 159770

Yoshida-gun, Fukui, Japan

Kyushu University Hospital /ID# 159688

Fukuoka, Fukuoka, Japan

Gunmaken Saiseikai Maebashi Hospital /ID# 160597

Maebashi, Gunma, Japan

National Hospital Organization Mito Medical Center /ID# 162988

Higashi Ibaraki-gun, Ibaraki, Japan

Kyoto Prefect Univ Med /ID# 160101

Kyoto, Kyoto, Japan

Tohoku University Hospital /ID# 161151

Sendai, Miyagi, Japan

Nagasaki University Hospital /ID# 160233

Nagasaki, Nagasaki, Japan

Osaka City University Hospital /ID# 159722

Osaka, Osaka, Japan

Kinki University -Osakasayama Campus /ID# 160777

Osakasayama-shi, Osaka, Japan

Tokyo Metropolitan Komagome Hospital /ID# 160759

Bunkyo-ku, Tokyo, Japan

Tokyo Jikei Daisan Hospital /ID# 159769

Komae-shi, Tokyo, Japan

NTT Medical Center Tokyo /ID# 160678

Shinagawa-ku, Tokyo, Japan

Yamagata University Hospital /ID# 161223

Yamagata, Yamagata, Japan

Akita University Hospital /ID# 160602

Akita, , Japan

Saitama Med Univ Int Med Ctr /ID# 161308

Hidaka, , Japan

NHO Nagoya Medical Center /ID# 159768

Nagoya, , Japan

Dokkyo Medical University Hosp /ID# 159650

Shimotsuga, , Japan

Juntendo University Hospital /ID# 159781

Tokyo, , Japan

Instituto Nacional de Cancerol /ID# 159269

Mexico City, Mexico City, Mexico

Centro de Invest Clin Chapulte /ID# 162625

Morelia, Michoacán, Mexico

Hosp. Univ. Dr. Jose E. Gonz /ID# 159268

Monterrey, Nuevo León, Mexico

North Shore Hospital /ID# 160132

Auckland, , New Zealand

Middlemore Clinical Trials /ID# 160131

Auckland, , New Zealand

Haukeland University Hospital /ID# 165630

Bergen, Hordaland, Norway

Sykehuset Ostfold Kalnes /ID# 165632

Grålum, , Norway

VA Caribbean Healthcare System /ID# 158999

San Juan, , Puerto Rico

Kemerovo Regional Clinical Hospital n.a. S.V. Belyaev /ID# 162991

Kemerovo, Kemerovo Oblast, Russia

Nizhniy Novgorod regional clinical hospital named N. A. Semashko /ID# 163186

Nizhny Novgorod, Nizhny Novgorod Oblast, Russia

State Institution of Health of the Ryazan Regional Clinical Hospital /ID# 163126

Ryazan, Ryazan Oblast, Russia

City Clinical Hospital Botkina /ID# 164086

Moscow, , Russia

Almazov North-West Federal Med /ID# 162170

Saint Petersburg, , Russia

Saint Petersburg State Institu /ID# 162171

Saint Petersburg, , Russia

Samara State Medical Universit /ID# 164173

Samara, , Russia

saratov state medical /ID# 163130

Saratov, , Russia

Yaroslavl Regional Clinic Hosp /ID# 162172

Yaroslavl, , Russia

Netcare Pretoria East Hospital /ID# 157373

Pretoria, Gauteng, South Africa

Tshwane District Hospital /ID# 157361

Pretoria, Gauteng, South Africa

Pusan National University Hosp /ID# 158725

Busan, Busan Gwang Yeogsi, South Korea

Chungnam National University Hospital /ID# 158726

Junggu, Daejeon Gwang Yeogsi, South Korea

Cath Univ Seoul St Mary's Hosp /ID# 158724

Seoul, Seoul Teugbyeolsi, South Korea

Seoul National University Hospital /ID# 162253

Seoul, , South Korea

Hospital Universitario y Politecnico La Fe /ID# 161181

Valencia, Valenciana, Spain

Hospital Infanta Leonor /ID# 161180

Madrid, , Spain

National Taiwan Univ Hosp /ID# 162781

Taipei City, Taipei, Taiwan

Tri-Service General Hospital /ID# 161683

Taipei City, Taipei, Taiwan

Kaohsiung Medical University /ID# 161693

Kaohsiung City, , Taiwan

Heartlands Hospital /ID# 163534

Birmingham, , United Kingdom

University Hospital of Wales /ID# 162726

Cardiff, , United Kingdom

Northwick Park Hospital /ID# 162727

Harrow, , United Kingdom

Countries

United States; Argentina; Australia; Belgium; Brazil; Canada; China; Czechia; France; Germany; Greece; Hungary; Ireland; Japan; Mexico; New Zealand; Norway; Puerto Rico; Russia; South Africa; South Korea; Spain; Taiwan; United Kingdom

References

Wei AH, Montesinos P, Ivanov V, DiNardo CD, Novak J, Laribi K, Kim I, Stevens DA, Fiedler W, Pagoni M, Samoilova O, Hu Y, Anagnostopoulos A, Bergeron J, Hou JZ, Murthy V, Yamauchi T, McDonald A, Chyla B, Gopalakrishnan S, Jiang Q, Mendes W, Hayslip J, Panayiotidis P. Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: a phase 3 randomized placebo-controlled trial. Blood. 2020 Jun 11;135(24):2137-2145. doi: 10.1182/blood.2020004856.

Reference Type: BACKGROUND

PMID: 32219442 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35829925 (View on PubMed)

Wei AH, Panayiotidis P, Montesinos P, Laribi K, Ivanov V, Kim I, Novak J, Stevens DA, Fiedler W, Pagoni M, Bergeron J, Ting SB, Hou JZ, Anagnostopoulos A, McDonald A, Murthy V, Yamauchi T, Wang J, Chyla B, Sun Y, Jiang Q, Mendes W, Hayslip J, DiNardo CD. 6-month follow-up of VIALE-C demonstrates improved and durable efficacy in patients with untreated AML ineligible for intensive chemotherapy (141/150). Blood Cancer J. 2021 Oct 1;11(10):163. doi: 10.1038/s41408-021-00555-8.

Reference Type: DERIVED

PMID: 34599139 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://www.rxabbvie.com/

Related Info

Other Identifiers

2016-003900-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2024-513630-37-00

Identifier Type: OTHER

Identifier Source: secondary_id

M16-043

Identifier Type: -

Identifier Source: org_study_id