Clinical Trial Details

NCT ID: NCT02993523
Date Last Changed: September 29, 2017


Research Study Summary

A clinical research study of Venetoclax, Azacitidine and Placebo for the treatment of Acute Myeloid Leukemia (AML)

Research Study 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 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 azacitidine works better than azacitidine on its own.

This is a Phase 3, randomized, double-blind (treatment is unknown to patients and doctors), placebo controlled 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 standard induction therapy (usual starting treatment). AbbVie is funding this study which will take place at approximately 150 hospitals globally and enrol approximately 400 patients.

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

Patients 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.

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Recruitment Details

18 to 99 Years
Overall Status
Lead Sponsor
36 Months
Facility Type


All ages 18 Years to 99 Years

Inclusion Criteria:

  • Participant must have confirmation of Acute Myeloid Leukemia (AML) by World Health Organization (WHO) criteria 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 before study enrollment.

  • Participant must have an ECOG Performance status:

  • 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

i. Subjects 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 FSH level > 40 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.

Exclusion Criteria:

  • Participant has received treatment with the following:

  • A hypomethylating agent and/or chemo therapeutic agent for Myelodysplastic syndrome (MDS).

  • Chimeric Antigen Receptor (CAR)-T cell therapy or other experimental therapies.

  • Experimental therapies for MDS or Acute Myeloid Leukemia (AML).

  • 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 is known to be positive for Human Immunodeficiency Virus (HIV) (HIV testing is not required).

  • Participant is known to be positive for hepatitis B or C infection with the exception of those with an undetectable viral load within 3 months. (Hepatitis B or C testing is not required). Participants with serologic evidence of prior vaccination to HBV [i.e., HBs Ag-, and anti-HBs+] may participate.

  • Participant has received strong and/or moderate CYP3A inducers within 7 days prior to the initiation of study treatment.

  • 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

  1. 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.

  • Participant has a white blood cell count > 25 × 10^9/L. (Hydroxyurea is permitted to meet this criterion.)

Site Locations (34)

Country State City Zip Facility and Contact
United States California Duarte 91010 City of Hope National Medical Center /ID# 154105
United States California Sacramento 95817 University of California, Davis Comprehensive Cancer Center /ID# 162725
United States Illinois Chicago 60637 The University of Chicago /ID# 154108
United States Indiana Fort Wayne 46804 Fort Wayne Medical Oncology and Hematology, Inc. /ID# 157190
United States Kansas Topeka 66606 Cotton-O'Neil Clinical Research Center /ID# 155136
United States Kentucky Louisville 40207 Norton Cancer Institute /ID# 154992
United States New York New York 10032 Columbia University Medical Center /ID# 154101
United States North Carolina Durham 27710 Duke Univ Medical Center /ID# 154106
United States Pennsylvania Pittsburgh 15232 University of Pittsburgh /ID# 154102
United States Texas Houston 77030 The University of Texas - MD Anderson Cancer Center /ID# 154100
United States Texas Temple 76508 Scott & White Memorial Hospital and Clinic /ID# 157191
United States Utah Salt Lake City 84112 University of Utah Huntsman Cancer Hospital /ID# 157192
Australia Adelaide 5000 Royal Adelaide Hospital /ID# 154271
Austria Graz 8036 Medical University Graz /ID# 157882
Austria Linz 4020 Krankenhaus der Elisabethinen Linz GmbH /ID# 154885
Austria Linz 4070 Krankenhaus der Barmherzigen Schwestern /ID# 154888
Austria Vienna 1140 Hanusch Krankenhaus der WGKK Wien /ID# 155676
Croatia Zagreb 10000 Klinicka bolnica Dubrava /ID# 153515
Finland Tampere 33520 Tampereen yliopistollinen sairaala /ID# 154963
Germany Halle 06120 Universitatsklinikum Halle (Saale) /ID# 153058
Germany Muenster D-48149 Universitatsklinikum Munster /ID# 153059
Hungary Budapest 1097 Egyesitett Szent Istvan es Szent Laszlo Korhaz /ID# 158990
Hungary Kaposvar 7400 Kaposi Mor Oktato Korhaz /ID# 153813
Israel Zerifin 70300 Assaf Harofeh Medical Center /ID# 158063
Italy padiglione Marcora 20122 Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico /ID# 152882
Italy Roma 00189 Azienda Ospedaliera Sant' Andrea /ID# 152876
Korea, Republic of Seoul 03080 Seoul National University Hospital /ID# 153675
Korea, Republic of Seoul 05030 Konkuk University Medical Center /ID# 153973
Korea, Republic of Seoul 06351 Samsung Medical Center /ID# 153674
Poland Chorzow 41-500 SPZOZ Zespol Szpitali Miejskich w Chorzowie /ID# 153385
Puerto Rico San Juan 00921 VA Caribbean Healthcare System (VACHS) /ID# 160507
Russian Federation Moscow 125284 City Clinical Hospital n.a. S.P. Botkina /ID# 155738
Russian Federation Ryazan 390039 Ryazan Regional Clinical Hospital /ID# 157460
Taiwan Kaohsiung 807 Kaohsiung Medical University Chung-Ho Memorial Hospital /ID# 153902


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