Venetoclax + Azacitidine for Acute Myeloid Leukemia

(Viale-a Trial)

Not currently recruiting at 296 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AbbVie

Must be taking: Azacitidine

Must not be taking: Hypomethylating agents, Venetoclax

Disqualifiers: HIV, Hepatitis B/C, CNS involvement, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 28

Duration: Variable (until disease progression or unacceptable toxicity)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding venetoclax to azacitidine is more effective than using azacitidine alone for treating acute myeloid leukemia (AML), a type of blood cancer. Venetoclax is an experimental drug that kills cancer cells by blocking a protein that helps them survive. The trial targets adults who have not been treated for AML before and cannot undergo standard intensive chemotherapy. Participants will receive either the new drug combination or a placebo with azacitidine to compare results. As a Phase 3 trial, this study is the final step before potential FDA approval, offering participants a chance to contribute to a treatment that could soon become widely available.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you have taken certain treatments like hypomethylating agents, venetoclax, or strong CYP3A inducers recently. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of venetoclax and azacitidine has been tested for safety in people with acute myeloid leukemia (AML). In earlier studies, most participants tolerated this combination well. Common side effects include nausea, diarrhea, and low blood cell counts, which are typical for AML treatments. Serious side effects can occur, but healthcare teams usually manage them closely.

The FDA has already approved venetoclax for other blood cancers, indicating general safety, though its use in AML remains under study. Since this study is in phase 3, the treatment has already demonstrated some safety and effectiveness in earlier research stages. However, individual experiences can vary, so participants should discuss any concerns with their healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for AML?

Researchers are excited about the Venetoclax and Azacitidine combination for treating Acute Myeloid Leukemia (AML) because it targets cancer cells in a novel way compared to standard chemotherapy options like cytarabine and daunorubicin. Venetoclax works by inhibiting a protein called BCL-2, which helps cancer cells survive. This mechanism is different because it directly triggers cancer cell death, potentially leading to more effective treatment outcomes. Additionally, when combined with Azacitidine, a drug that modifies DNA to reactivate tumor-suppressing genes, it may enhance the overall anti-cancer effect, offering hope for better responses in patients with AML.

What evidence suggests that this trial's treatments could be effective for acute myeloid leukemia?

Research has shown that adding venetoclax to azacitidine can treat acute myeloid leukemia (AML) more effectively. In this trial, some participants will receive both venetoclax and azacitidine, while others will receive azacitidine with a placebo. One study found that patients who received both venetoclax and azacitidine lived longer than those who received only azacitidine, specifically increasing the average survival time. Another study demonstrated that this combination is effective even for older patients, who typically have a worse prognosis. Real-world evidence also supports using venetoclax and azacitidine together, showing it to be both practical and effective. These findings suggest that the combination treatment could be more effective for AML than azacitidine alone. ^{1 6 7 8 9}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

This trial is for adults diagnosed with Acute Myeloid Leukemia (AML) who haven't been treated before and can't have standard chemotherapy due to age or health issues. They must be expected to live at least 12 weeks, able to consent, and if of childbearing potential, agree to use birth control.

Inclusion Criteria

I am over 18 and can care for myself, but my ability to do daily activities may vary with my age.

My kidneys work well enough, with a creatinine clearance rate of at least 30 mL/min.

I am a woman who can have children and my pregnancy test is negative.

Exclusion Criteria

I am currently being treated for a serious infection.

Participant is currently participating in another research or observational study.

I have had CAR-T cell therapy or experimental treatments for my blood cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive venetoclax or placebo with azacitidine in 28-day cycles until disease progression or unacceptable toxicity

Variable (until disease progression or unacceptable toxicity)

Monthly visits for each 28-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years after the last participant is randomized

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Azacitidine
• Placebo
• Venetoclax

Trial Overview The study tests whether Venetoclax combined with Azacitidine is more effective than Azacitidine alone in treating AML. It's a Phase 3 trial where two-thirds of the patients will receive both drugs while one-third will get a placebo with Azacitidine.

How Is the Trial Designed?

Group I: Group 1 and Group 2: Venetoclax 100 mg/200 mg/400 mg + Azacitidine 75 mg/m^2 Active Control 2 Interventions

Participants enrolled under original protocol and enrolled during or after protocol amendment 1 received venetoclax 100 mg, once orally, on Day 1 of Cycle 1 followed by venetoclax 200 mg, once orally, on Day 2 of Cycle 1 and venetoclax 400 mg, orally, QD, on Day 3 to Day 28 of each 28 day cycle along with azacitidine 75 mg/m\^2, SC or IV, QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).

Group II: Open Label China Cohort: Venetoclax 400 mg + Azacitidine 75 mg/m^2 Active Control 2 Interventions

Participants received venetoclax 400 mg, orally, QD, from Day 1 to Day 28 of each 28 day cycle along with azacitidine 75 mg/m\^2, SC, QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).

Group III: Group 1 and Group 2: Placebo + Azacitidine 75 mg/m^2 Placebo Group 2 Interventions

Participants enrolled under original protocol and enrolled during or after protocol amendment 1 received venetoclax-matching placebo, orally, every day (QD), from Day 1 to Day 28 of each 28 day cycle along with azacitidine 75 mg/m\^2, subcutaneously (SC) or intravenously (IV), QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).

Azacitidine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Vidaza for:

• Acute myeloid leukemia
• Chronic myelomonocytic leukemia
• Myelodysplastic syndromes

Approved in United States as Vidaza for:

• Myelodysplastic syndromes
• Chronic myelomonocytic leukemia

Approved in Canada as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Approved in Japan as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Who Is Running the Clinical Trial?

AbbVie

Lead Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Published Research Related to This Trial

In a phase II study involving 60 older or unfit patients with newly diagnosed acute myeloid leukemia (AML), the combination of venetoclax with cladribine and low-dose cytarabine alternating with venetoclax and 5-azacitidine resulted in a high composite complete response rate of 93%.

The treatment showed promising overall survival and disease-free survival rates, with only one death occurring within 4 weeks, indicating that this regimen is effective and has a favorable safety profile for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Study of Venetoclax Added to Cladribine Plus Low-Dose Cytarabine Alternating With 5-Azacitidine in Older Patients With Newly Diagnosed Acute Myeloid Leukemia. Kadia, TM., Reville, PK., Wang, X., et al.[2023]

In a Japanese subgroup of the phase 3 VIALE-A trial, venetoclax-azacitidine significantly improved overall survival rates compared to placebo-azacitidine, with 67% of patients alive at 12 months versus 46% in the placebo group.

The treatment also resulted in a high complete response (CR) and CR with incomplete hematologic recovery (CRi) rate of 67%, while maintaining a safety profile similar to the global study, indicating it is a viable first-line treatment for Japanese patients with acute myeloid leukemia ineligible for intensive chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax plus azacitidine in Japanese patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy. Yamamoto, K., Shinagawa, A., DiNardo, CD., et al.[2023]

In a study of 50 adults with acute myeloid leukemia (AML) in Mexico and Peru, venetoclax-based therapy showed a high complete response rate of 78.6% in newly diagnosed patients and 45.5% in those with relapsed/refractory disease, indicating its efficacy in treating AML.

The median overall survival was 9.6 months for newly diagnosed patients and 8 months for relapsed/refractory patients, suggesting that venetoclax is a viable treatment option even in real-world settings, despite common hematologic toxicities and dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax-based combinations for acute myeloid leukemia: optimizing their use in Latin-America. Gómez-De León, A., Demichelis-Gómez, R., Pinedo-Rodríguez, A., et al.[2022]

In a phase 1/2 study involving six Japanese patients aged 60 and older with acute myeloid leukaemia, the combination of venetoclax and azacitidine demonstrated a high response rate, with 83% of patients achieving a response, including three complete remissions.

The treatment was generally well tolerated, with a median overall survival of 15.7 months, although some patients experienced serious adverse events, including grade 3 fungal pneumonia, which required treatment adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax in combination with azacitidine in Japanese patients with acute myeloid leukaemia: phase 1 trial findings. Taniguchi, S., Yamauchi, T., Choi, I., et al.[2021]

In patients with newly diagnosed unfit acute myeloid leukemia (AML), the combination of azacitidine and venetoclax is a standard first-line treatment.

However, patients with TP53-mutated AML and poor-risk cytogenetics do not benefit from adding venetoclax to azacitidine, suggesting that alternative treatment regimens should be considered for these individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TP53 or Not TP53: That Is the Question. Green, SD., Zeidner, JF.[2023]

In a study of 13 patients with acute leukemia treated with venetoclax and azacitidine, 46% developed COVID-19, highlighting a significant risk associated with this treatment during the pandemic.

The study found that 33% of those who contracted COVID-19 died from the virus, indicating that COVID-19 can lead to severe outcomes in patients receiving AZA-VEN therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SARS-CoV-2 Infection in Patients Treated with Azacitidine and Venetoclax for Acute Leukemia: A Report of a Case Series Treated in a Single Institution. Drozd-Sokołowska, J., Mądry, K., Barankiewicz, J., et al.[2023]

In a study of 57 elderly patients (average age 69.9 years) with acute myeloid leukemia, the combination of venetoclax and azacitidine (VEN + AZA) showed a high overall response rate of 87.5% and a complete remission (CR) rate of 68.8%, indicating strong efficacy in this population.

The treatment was associated with a median overall survival (OS) of 11.5 months, and achieving minimal residual disease (MRD) negativity (<0.1%) was more common with VEN + AZA compared to traditional chemotherapy, although older patients (≥75 years) and those with higher ECOG scores faced more challenges in achieving MRD negativity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-institution experience of venetoclax combined with azacitidine in newly diagnosed acute myeloid leukemia patients. Yu, H., Wang, C., Lei, Y., et al.[2023]

Citations

1. nature.com nature.com/articles/s41375-025-02730-3

Outcomes of patients treated with venetoclax plus ... Measurable residual disease response and prognosis in treatment-naïve acute myeloid leukemia with venetoclax and azacitidine. J Clin Oncol ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12135334/

Efficacy and safety of venetoclax and azacitidine for acute ... The salvage therapy outcomes in patients with treatment-naïve AML after AZA-VEN suggested best outcomes for VEN-AZA combined with a targeted ...

3. venclextahcp.com venclextahcp.com/aml/efficacy/ven-aza/survival-results.html

VEN+AZA: Overall survival (OS) data from the VIALE-A trial See median overall survival data for VENCLEXTA® combined with azacitidine compared with azacitidine. See full safety and Prescribing Info for more details.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40951718/

Real-world outcomes of azacitidine plus venetoclax in ... This real-world practice highlights the feasibility and effectiveness of AZA-VEN in combination with antifungal prophylaxis for elderly or ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa2012971

Azacitidine and Venetoclax in Previously Untreated Acute ... Older patients with acute myeloid leukemia (AML) have a dismal prognosis, even after treatment with a hypomethylating agent. Azacitidine ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6499443/

Evaluating venetoclax and its potential in treatment-naïve ... Relapsed acute myeloid leukemia is less sensitive to venetoclax + azacitidine due to leukemia stem cell resistance driven by fatty acid metabolism and can ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04161885

NCT04161885 | A Study Evaluating Safety and Efficacy of ... The main objective of this study is to evaluate the efficacy of venetoclax in combination with azacitidine to improve Overall Survival (OS) in Acute Myeloid ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02203773

NCT02203773 | Study of ABT-199 (GDC-0199) in ... This is a Phase 1b, open-label, non-randomized, multicenter study to evaluate the safety and pharmacokinetics of orally administered venetoclax (ABT-199) ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S0006497118473065

A Phase 1b Study of Venetoclax (ABT-199/GDC-0199) in ... Venetoclax (VEN) is a selective, potent, orally bioavailable BCL-2 inhibitor that has demonstrated single-agent activity in AML cell lines, primary pt samples, ...