Viale-a

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

Brief 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.

The active drug 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 an active drug 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 an active drug 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.

Interventional study

Status:
Active, not recruiting
Conditions:
Acute Myeloid Leukemia (AML)
Enrollment:
400 patients
Phase:
  • 1
  • 2
  • 3
  • 4
Protocol ID:
M15-656
Allocation:
Randomized
Intervention model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Purpose:
Treatment

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Eligibility criteria

Participant attributes:
Male and Female

Age:

18 Years and older.

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.)

All the cities where the clinical studies are located

Calgary - T2N 4N2
Vancouver - V6Z 1Y6
Hamilton - L8V 1C3
Ottawa - K1H 8L6
Toronto - M5G 2M9

Alberta

British Columbia