Azacitidine + Venetoclax for Acute Myeloid Leukemia

Overseen By Tapan Kadia, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Tyrosine kinase inhibitors

Disqualifiers: APL, Active CNS disease, 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: 1

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of two chemotherapy drugs, azacitidine and venetoclax, in treating acute myeloid leukemia (AML) during remission. These drugs aim to stop cancer cells from growing, dividing, or spreading. The trial suits adults with AML who are in their first remission and not yet ready for a stem cell transplant. Participants should have undergone specific chemotherapy treatments to achieve remission. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to the development of potentially effective therapies.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it is common for clinical trials to have specific requirements, so it's best to discuss your current medications with the trial coordinators.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that azacitidine and venetoclax are likely to be safe for humans?

Research has shown that patients with acute myeloid leukemia (AML) generally tolerate the combination of azacitidine and venetoclax well. While side effects can occur, they are usually manageable. Common side effects include low blood counts, nausea, and tiredness, which are typical of chemotherapy treatments. Additionally, the FDA has already approved venetoclax for use in some AML patients, indicating a certain level of safety. This combination works to stop cancer cells from growing and dividing, offering a treatment option for those in remission. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for acute myeloid leukemia?

Researchers are excited about Azacitidine and Venetoclax for treating Acute Myeloid Leukemia (AML) because they offer unique mechanisms of action compared to standard chemotherapy options like cytarabine and daunorubicin. Azacitidine is a hypomethylating agent that works by reactivating tumor suppressor genes, while Venetoclax targets and inhibits the BCL-2 protein, which cancer cells use to avoid cell death. This combination aims to attack AML cells more effectively by using these complementary approaches, potentially leading to better outcomes for patients.

What evidence suggests that azacitidine and venetoclax might be an effective treatment for acute myeloid leukemia?

Research has shown that using azacitidine and venetoclax together effectively treats acute myeloid leukemia (AML), particularly in patients unable to tolerate stronger treatments. Studies have found that this combination can inhibit the growth of cancer cells. In a real-world study, many older patients with AML responded well to this treatment and showed significant improvement. This trial will evaluate the combination of azacitidine and venetoclax, already recognized as a standard care option for some AML patients. Overall, evidence supports that azacitidine and venetoclax together can be a strong option for managing AML. ^{2 6 7 8 9}

Who Is on the Research Team?

Tapan Kadia, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Acute Myeloid Leukemia (AML) in their first remission who aren't going for a stem cell transplant right away. They must have finished induction therapy and at least one consolidation cycle if they had intensive treatment, or two cycles of lower intensity therapy. Participants need to be healthy enough overall, not pregnant or breastfeeding, willing to use contraception, and without certain other serious illnesses.

Inclusion Criteria

I agree to use birth control or abstain from sex during and 30 days after treatment.

My bone marrow functions well.

- Have a negative serum or urine pregnancy test within 10 to 14 days of enrolling

Exclusion Criteria

I have an active brain or spinal cord disease.

I have been diagnosed with a specific type of leukemia (APL or AML-M3).

I do not have any severe illnesses or social situations that would stop me from following the study's requirements.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive azacitidine subcutaneously or intravenously over 1 hour daily on days 1-5, and venetoclax orally daily on days 1-14. Treatment repeats every 28 days for up to 24 cycles.

24 months

Monthly visits for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-ups at 30 days and then every 6-12 months.

10 years

1 visit at 30 days, then biannual to annual visits

What Are the Treatments Tested in This Trial?

Interventions

• Azacitidine
• Venetoclax

Trial Overview The study is testing the effectiveness of azacitidine combined with venetoclax as maintenance therapy for AML patients in remission. It aims to see how these chemotherapy drugs work together to prevent cancer cells from growing by killing them or stopping their division and spread.

How Is the Trial Designed?

Group I: Treatment (azacytidine, venetoclax) Experimental Treatment 2 Interventions

Patients receive azacitidine SC or IV over 1 hour daily on days 1-5, and venetoclax PO daily on days 1-14. Treatment repeats every 28 days for up to 24 cycles 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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

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 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 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 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 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 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 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]

In a study of 60 patients with acute myeloid leukemia (AML), the combination of venetoclax and azacitidine (Ven+AZA) demonstrated a high response rate, with 70.8% of previously untreated patients unfit for standard chemotherapy achieving complete remission (CR) or CR with incomplete hematological recovery (CRi) after one cycle.

Ven+AZA was found to be safe and tolerable, with some patients achieving minimal residual disease (MRD) negativity, particularly in those with favorable genetic mutations like NPM1, IDH1/IDH2, and TP53, indicating its potential effectiveness in specific patient subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Short-term efficacy of venetoclax combined with azacitidine in acute myeloid leukemia: a single-institution experience]. Yu, WJ., Jia, JS., Wang, J., et al.[2022]

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]

Citations

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

Outcomes of patients treated with venetoclax plus ... Venetoclax plus azacitidine is recognized as standard of care for patients with acute myeloid leukemia (AML) ineligible for intensive ...

2. 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 ...

3. 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 ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2950328024000177

Real-world outcomes of newly diagnosed AML treated with ... Here we report a large real-world cohort of 654 patients treated in 53 UK hospitals with either venetoclax and azacitidine (n=587) or LDAC (n=67).

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

Efficacy of Venetoclax Combined with Azacitidine in Elderly ... Dose of Venetoclax in Combination with Hypomethylating Agents and Outcomes of Patients with Acute Myeloid Leukemia: A Retrospective Study.

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/PMC10100228/

A phase 1b study of venetoclax and azacitidine ... In this phase‐1b study, we evaluated the safety of venetoclax either alone or in combination with azacitidine therapy after HMA failure. Due to the limited ...

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

Efficacy and safety of venetoclax plus azacitidine based ... This meta-analysis aimed to evaluate the efficacy and safety of venetoclax plus azacitidine (VEN + AZA) regimens in patients with relapsed ...

9. ashpublications.org ashpublications.org/blood/article/145/12/1237/517960/How-I-treat-patients-with-AML-using-azacitidine

How I treat patients with AML using azacitidine and venetoclax Venetoclax (VEN) received full approval in October 2020 for use in older patients who are unfit with acute myeloid leukemia (AML) combined with either ...