Phase 3
N=443
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
Acute Myeloid Leukemia (AML)
Bottom Line
View on ClinicalTrials.gov: NCT02993523 ↗Enrolled (actual)
443
Serious AEs
82.4%
Results posted
Jan 2023
Primary outcome: Primary: Overall Survival (OS) — 9.6; 14.7 months — p=<0.001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Azacitidine (Drug); Venetoclax (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- AbbVie
- Primary completion
- Dec 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Overall Survival (OS) |
9.6; 14.7 | <0.001 sig |
| PRIMARY Percentage of Participants With Complete Remission (CR) and Complete Remission With Incomplete Marrow Recovery (CRi) |
17.9; 38.8; 60.0; 11.0; 28.0; 20.0 | <0.001 sig |
| SECONDARY Event-free Survival (EFS) |
— | — |
| SECONDARY Global Health Status/Quality of Life (GHS/QoL) |
— | — |
| SECONDARY Percentage of Participants Achieving Composite Complete Remission (CR or CRi) |
— | — |
| SECONDARY Complete Remission or Complete Remission With Partial Hematologic Recovery Rate (CR+CRh) |
— | — |
| SECONDARY Post Baseline Transfusion Independence Rate |
— | — |
| SECONDARY Complete Remission (CR) Rate |
— | — |
| SECONDARY Fatigue/Quality of Life (QoL) |
— | — |
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.
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 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.
Eligibility Criteria
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 = 30 mL/min to 1.5 to = 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) 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.
Exclusion Criteria
- 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.
- 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 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 HB
Data sourced from ClinicalTrials.gov (NCT02993523). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.