A Study of Venetoclax in Combination With Azacitidine Versus Azacitidine in Treatment Naïve Subjects With Acute Myeloid Leukemia Who Are Ineligible for Standard Induction Therapy



Status:Recruiting
Conditions:Blood Cancer, Blood Cancer, Hematology
Therapuetic Areas:Hematology, Oncology
Healthy:No
Age Range:18 - Any
Updated:3/24/2019
Start Date:February 2, 2017
End Date:May 23, 2021
Contact:ABBVIE CALL CENTER
Email:abbvieclinicaltrials@abbvie.com
Phone:847.283.8955

Use our guide to learn which trials are right for you!

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 180 hospitals globally and enroll 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.


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. Subjects 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 FSH level > 40 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 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
HBV DNA 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.)
We found this trial at
25
sites
33 Whiting Hill Road
Brewer, Maine 04412
?
mi
from
Brewer, ME
Click here to add this to my saved trials
Atlanta, Georgia 30322
?
mi
from
Atlanta, GA
Click here to add this to my saved trials
Baltimore, Maryland 21287
?
mi
from
Baltimore, MD
Click here to add this to my saved trials
Boston, Massachusetts 02114
?
mi
from
Boston, MA
Click here to add this to my saved trials
Boston, Massachusetts 02215
?
mi
from
Boston, MA
Click here to add this to my saved trials
Boston, Massachusetts 02215
?
mi
from
Boston, MA
Click here to add this to my saved trials
Burlington, Vermont 05401
?
mi
from
Burlington, VT
Click here to add this to my saved trials
5801 South Ellis Avenue
Chicago, Illinois 60637
?
mi
from
Chicago, IL
Click here to add this to my saved trials
?
mi
from
Chicago, IL
Click here to add this to my saved trials
Duarte, California 91010
?
mi
from
Duarte, CA
Click here to add this to my saved trials
2301 Erwin Road
Durham, North Carolina 27710
?
mi
from
Durham, NC
Click here to add this to my saved trials
Fort Wayne, Indiana 46804
?
mi
from
Fort Wayne, IN
Click here to add this to my saved trials
100 Michigan Street Northeast
Grand Rapids, Michigan 49503
?
mi
from
Grand Rapids, MI
Click here to add this to my saved trials
Houston, Texas 77030
?
mi
from
Houston, TX
Click here to add this to my saved trials
?
mi
from
Los Angeles, CA
Click here to add this to my saved trials
3991 Dutchmans Lane
Louisville, Kentucky 40207
?
mi
from
Louisville, KY
Click here to add this to my saved trials
?
mi
from
Nashville, TN
Click here to add this to my saved trials
?
mi
from
New York, NY
Click here to add this to my saved trials
?
mi
from
New York, NY
Click here to add this to my saved trials
Pittsburgh, Pennsylvania 15260
?
mi
from
Pittsburgh, PA
Click here to add this to my saved trials
Sacramento, California 95817
?
mi
from
Sacramento, CA
Click here to add this to my saved trials
Salt Lake City, Utah 84112
?
mi
from
Salt Lake City, UT
Click here to add this to my saved trials
?
mi
from
Temple, TX
Click here to add this to my saved trials
?
mi
from
Topeka, KS
Click here to add this to my saved trials
Woolloongabba, Queensland
?
mi
from
Woolloongabba,
Click here to add this to my saved trials