Azacitidine/Decitabine + Venetoclax for Acute Myeloid Leukemia

Recruiting at 3 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Brian Jonas

Must be taking: Decitabine, Azacitidine

Must not be taking: CYP3A inducers

Disqualifiers: HIV, Hepatitis, CNS involvement, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 1 year

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of three chemotherapy drugs—azacitidine, decitabine, and venetoclax—for treating acute myeloid leukemia (AML). The goal is to determine the effectiveness of these drugs in stopping cancer cell growth in individuals whose AML is either untreated or has returned after treatment. It suits those diagnosed with AML who have previously used azacitidine or decitabine for another blood condition and are either new to AML treatment or have relapsed. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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 use other investigational agents or certain anticancer therapies close to starting the trial. It's best to discuss your specific 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 azacitidine and venetoclax is generally well-tolerated by people with acute myeloid leukemia (AML). Studies have found that this combination works better than azacitidine alone. Most people can handle this combination without serious problems.

Earlier research also supports the safety of the decitabine and venetoclax combination. It has been tested in older patients with AML, who often do not respond well to standard treatments. This combination has shown promise in being safe for these patients.

Both combinations have been studied in different situations, and while side effects can occur, they are usually manageable. These findings suggest that the treatments are safe for most patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of azacitidine or decitabine with venetoclax for treating Acute Myeloid Leukemia (AML) because it offers a fresh approach compared to standard treatments like intensive chemotherapy. Unlike traditional therapies, venetoclax targets and inhibits a protein called BCL-2, which helps cancer cells survive, making them more vulnerable to the effects of azacitidine or decitabine. This combination aims to enhance the effectiveness of these existing drugs and potentially improve outcomes for patients who may not be candidates for aggressive chemotherapy. Additionally, this regimen could offer a less intensive treatment option with the convenience of oral administration for venetoclax, potentially improving patient quality of life during treatment.

What evidence suggests that azacitidine, decitabine, and venetoclax could be effective for acute myeloid leukemia?

This trial will evaluate the combination of azacitidine or decitabine with venetoclax for treating acute myeloid leukemia (AML). Research has shown that combining azacitidine with venetoclax results in a response rate of about 38.5% in AML patients, with an average survival of about 16.9 months. Similarly, combining decitabine with venetoclax proves as effective as traditional chemotherapy but with fewer side effects. These treatments offer hope, especially for those newly diagnosed or who have relapsed, by stopping cancer cells from growing and dividing. Participants in this trial will receive either azacitidine or decitabine, along with venetoclax, based on their prior treatment history. ^{6 7 8 9 10}

Who Is on the Research Team?

Brian Jonas, MD

Principal Investigator

University of California, Davis

Are You a Good Fit for This Trial?

Adults diagnosed with acute myeloid leukemia (AML) who have not been treated for AML before or whose AML has returned. They must have previously failed treatment with hypomethylating agents for a related blood disorder and be able to take oral medication. Women of childbearing age must test negative for pregnancy and agree to use contraception, as should men with partners of childbearing potential.

Inclusion Criteria

Total bilirubin =, 1.5 x institution's ULN unless related to AML or Gilbert's syndrome

My diagnosis is AML, confirmed by the latest WHO criteria.

I had a bone marrow transplant for a blood disorder more than 3 months ago.

Exclusion Criteria

I have been diagnosed with acute promyelocytic leukemia.

I am not using, and do not plan to use, any experimental drugs within 14 days before starting venetoclax.

I haven't taken strong or moderate CYP3A inducers in the last week.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive azacitidine or decitabine and venetoclax. Azacitidine is administered IV or SC on days 1-7, or decitabine IV on days 1-5, and venetoclax PO daily on days 1-28. Cycles repeat every 28 days.

Up to 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment, including overall response rate and measurable residual disease status.

Up to 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Azacitidine
• Decitabine
• Venetoclax

Trial Overview

The trial is testing the combination of chemotherapy drugs azacitidine or decitabine with venetoclax in patients with AML that's either new or has come back after previous treatments. The goal is to see how well these drugs work together in stopping cancer cell growth by killing them, halting division, or preventing spread.

How Is the Trial Designed?

Group I: Treatment (azacitidine, decitabine, venetoclax) Experimental Treatment 3 Interventions

Patients receive azacitidine IV over 10-40 minutes or SC on days 1-7 (for patients with prior decitabine use), or decitabine IV on days 1-5 (for patients with prior azacitidine), and venetoclax PO daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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?

Brian Jonas

Lead Sponsor

Trials

5

Recruited

80+

AbbVie

Industry 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

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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 a study of nine AML patients with acquired resistance to venetoclax, the typical BCL2 mutation associated with resistance was not found, suggesting that this mutation is not necessary for developing resistance in AML.

The study identified that existing mutations, particularly the expansion of FLT3-ITD, were primarily responsible for venetoclax resistance, indicating that monitoring these mutations could help in developing strategies to prevent or overcome resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Not BCL2 mutation but dominant mutation conversation contributed to acquired venetoclax resistance in acute myeloid leukemia. Zhang, X., Qian, J., Wang, H., et al.[2022]

The VA regimen, combining venetoclax and azacitidine, demonstrated a high complete remission (cCR) rate of 78.8% after the first treatment cycle and 81.8% after prolonged treatment in 66 patients with newly diagnosed acute myeloid leukemia (AML) who were not suitable for conventional chemotherapy.

The treatment was generally safe, with manageable adverse effects, primarily neutropenia, thrombocytopenia, and anemia, and showed better outcomes in patients with specific gene mutations (IDH1/2 or NPM1) and those experiencing rebound thrombocytosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy of venetoclax combined azacitidine in newly diagnosed acute myeloid leukemia unfit for standard chemotherapy: a single center experience]. Sun, L., Ye, SJ., Zhou, N., et al.[2023]

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 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 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 45 elderly patients with relapsed acute myeloid leukemia, the combination of venetoclax (VEN) and azacitidine (AZA) resulted in a significantly higher overall remission rate (ORR) of 77.8% compared to 37.0% for the CAG regimen with decitabine (DAC), indicating better efficacy for the VEN and AZA combination.

The VEN and AZA treatment was associated with lower incidences of severe adverse events, such as grade Ⅲ-Ⅳ cytopenia and infections, suggesting it is a safer option for elderly patients compared to the CAG with DAC regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of venetoclax combined with azacitidine versus CAG regimen combined with decitabine in elderly patients with relapsed acute myeloid leukemia]. Wang, P., Zhang, LW., Lu, CQ., et al.[2022]

Citations

1.

nature.com

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

Outcomes of patients treated with venetoclax plus ...

The 5-year relative survival of patients with AML is ~32%, and survival rates are dependent on age at diagnosis. Patients <50 years of age have ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12422247/

Efficacy of Venetoclax Combined with Azacitidine in Elderly ...

Venetoclax combined with azacitidine has shown promising activity in newly diagnosed or relapsed/refractory AML, but real-world data on older ...

3.

hematologyadvisor.com

hematologyadvisor.com/news/combination-azacitidine-venetoclax-acute-myeloid-leukemia-aml-treatment-risk/

Combination Azacitidine, Venetoclax Effective in AML ...

Analysis showed that the overall response rates in the azacitidine plus venetoclax, chemotherapy, and azacitidine monotherapy groups were 38.5%, ...

4.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa2012971

Azacitidine and Venetoclax in Previously Untreated Acute ...

At a median follow-up of 14.9 months, the median overall survival was 16.9 months. This confirmatory trial (VIALE-A) was designed to evaluate ...

5.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e18509

Comparative safety and effectiveness of azacitidine plus ...

In AML patients aged 60–75 years, HMA&Ven demonstrated comparable all-cause mortality to IC and significantly lower risk of several adverse events.

6.

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 ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10928973/

Meta‑analysis of the efficacy of venetoclax and azacitidine ...

The combination of venetoclax and azacitidine demonstrated greater overall efficacy than azacitidine monotherapy for AML treatment.

8.

sciencedirect.com

sciencedirect.com/science/article/pii/S0006497118473065

A Phase 1b Study of Venetoclax (ABT-199/GDC-0199) in ...

None of the pts with objective response experienced relapse of AML. Conclusions: Combination therapy of VEN with DEC or AZA demonstrates a tolerable safety ...

9.

link.springer.com

link.springer.com/article/10.1007/s00277-025-06643-0

Efficacy and safety of venetoclax plus azacitidine based ...

The previous study also reported a significantly higher CR/CRi rate of 67.5% for newly diagnosed (ND) AML patients treated with VEN + AZA, ...

10.

tandfonline.com

tandfonline.com/doi/full/10.1080/16078454.2023.2198098

Full article: The efficacy and safety of venetoclax and ...

The meta-analysis sought to evaluate the efficacy and safety of a combination of venetoclax (Ven) and azacitidine (AZA) in the treatment of acute myeloid ...