Azacitidine + Venetoclax for Acute Myeloid Leukemia

Recruiting at 6 trial locations

Overseen By Eytan Stein, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Venetoclax

Disqualifiers: APL, Blast crisis, Infections, 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: 4

Duration: 4 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether combining azacitidine (a chemotherapy drug) and venetoclax (a targeted therapy) can effectively reduce or eliminate measurable residual disease (MRD) in individuals with acute myeloid leukemia (AML) who have received standard chemotherapy and plan to undergo a bone marrow transplant. The goal is to determine if this approach can lower the risk of cancer recurrence after the transplant. This trial may suit those with AML (excluding acute promyelocytic leukemia), who have completed two rounds of intensive chemotherapy, are in remission but still have some MRD, and are eligible for a bone marrow transplant. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

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

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

Research has shown that patients generally tolerate the combination of azacitidine and venetoclax well. In studies, many patients managed these treatments without major issues. Specifically, azacitidine and venetoclax present a lower risk of certain side effects compared to other treatments for acute myeloid leukemia (AML). For example, in older patients, this combination offered similar survival rates to other options but with fewer negative side effects.

Overall, evidence suggests that this treatment pair is safe for patients with AML, although individual experiences can differ. Discussing any concerns with a healthcare provider is always important. ^{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 this combo offers a fresh approach compared to traditional chemotherapy. Most AML treatments rely on strong chemotherapy drugs to destroy cancer cells, which can be harsh and have significant side effects. However, Venetoclax targets a specific protein that cancer cells need to survive, potentially leading to more precise cancer cell destruction with fewer side effects. Meanwhile, Azacitidine helps by altering the way cancer cells express genes, making them more vulnerable to treatment. This combination has the potential to be more effective and less taxing on the body than standard treatments.

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 can be promising for treating acute myeloid leukemia (AML). Many patients entered remission, with their cancer no longer detectable after treatment. Studies have found that this combination extends patients' lives compared to those who received a placebo. In one study, patients treated with these drugs lived for a median of 16.9 months. This suggests that azacitidine and venetoclax can effectively reduce AML symptoms and may help patients live longer. ^{1 2 3 6 7}

Who Is on the Research Team?

Eytan Stein, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with Acute Myeloid Leukemia (AML) who've had standard chemotherapy and are candidates for a stem cell transplant. It's aimed at reducing residual leukemia cells to prevent relapse.

Inclusion Criteria

I have been diagnosed with a specific type of leukemia (AML) that was not caused by another cancer treatment.

Patient is willing and able to adhere to the study visit schedule and other protocol requirements.

I have completed 2 rounds of strong chemotherapy.

Exclusion Criteria

Patient has mechanical heart valve.

I have a condition that affects my ability to swallow or absorb pills.

My condition is an advanced stage of chronic myeloid leukemia.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Azacitidine and Venetoclax to reduce measurable residual disease (MRD) in AML patients

4 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including MRD status assessment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Azacitidine
• Venetoclax

Trial Overview

The study tests the combination of two drugs, Azacitidine and Venetoclax, to see if they can effectively reduce or eliminate remaining leukemia cells in AML patients before undergoing a bone marrow transplant.

How Is the Trial Designed?

Group I: Azacitidine and Venetoclax Experimental Treatment 2 Interventions

Cycle length: 28 days Azacitidine 75 mg/m2 daily, on days 1-7, given IV or SC (generally given IV in our institution) Venetoclax 400 mg orally daily on days 1-28

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

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 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 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 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 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 20 elderly patients with relapsed refractory acute myeloid leukemia (AML), the combination of azacytidine and venetoclax showed a total treatment efficiency of 90%, significantly higher than the 40% efficiency observed with azacytidine alone.

The combination treatment improved hematological parameters, such as platelet and white blood cell counts, while maintaining a similar safety profile to azacytidine alone, indicating it is a promising option for enhancing treatment efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of the Clinical Efficacy of Azacytidine + Venetoclax in the Treatment of Elderly Patients with Relapsed Refractory Acute Myeloid Leukemia. Wang, W., Luo, Q., Chen, Q., et al.[2023]

In a study of 6 children with refractory or relapsed acute myeloid leukemia (AML), the combination of venetoclax, azacitidine, and cladribine (VAC regimen) resulted in significant treatment responses, with 4 achieving complete remission and 1 showing partial remission.

Despite severe side effects like grade IV neutropenia and thrombocytopenia, there were no treatment-related deaths or infections, indicating that the VAC regimen is both effective and safe for this vulnerable patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Safety and the Short-Term Efficacy of Venetoclax Combined with Azacitidine Followed by Cladribine in Children with Refractory/Relapsed Acute Myeloid Leukemia]. DU, WW., Liu, SX., Wang, Y., 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 the HiDDAV study involving 42 newly diagnosed AML patients, higher doses of venetoclax (600 mg daily) were found to be tolerable but did not show significant clinical improvement compared to the standard 400 mg dose.

The study revealed that using minimal residual disease (MRD) status to guide the discontinuation of azacitidine did not lead to better outcomes in terms of duration of response or overall survival, suggesting that alternative strategies are needed to optimize treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Higher-dose venetoclax with measurable residual disease-guided azacitidine discontinuation in newly diagnosed acute myeloid leukemia. Gutman, JA., Winters, A., Kent, A., et al.[2023]

A lower dosage of Venetoclax (100 mg) combined with Azacitidine showed favorable outcomes in newly diagnosed acute myeloid leukemia (AML) patients, with a median overall survival of 17 months and an overall response rate of 69.4% based on a study of 36 patients.

The study suggests that even with dose reductions of Venetoclax, the combination therapy remains effective, indicating a potential strategy to manage therapy-related toxicity while still achieving significant treatment responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced duration and dosage of venetoclax is efficient in newly diagnosed patients with acute myeloid leukemia. Cui, J., Chen, X., Li, C., et al.[2023]

Citations

1.

pubmed.ncbi.nlm.nih.gov

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

Real-world outcomes of azacitidine plus venetoclax in ...

After treatment, more than half went into remission (the cancer was no longer detectable), and those with newly diagnosed AML had better ...

2.

nature.com

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

Outcomes of patients treated with venetoclax plus ...

Efficacy, including composite complete remission and overall survival, were improved with venetoclax plus azacitidine vs. placebo plus ...

3.

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 ...

4.

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%, ...

5.

ashpublications.org

ashpublications.org/bloodneoplasia/article/1/3/100017/516192/Real-world-outcomes-of-newly-diagnosed-AML-treated

Real-world outcomes of newly diagnosed AML treated with ...

In the VIALE-A study, venetoclax combined with azacitidine improved the median overall survival (OS) from 9.6 to 14.7 months, compared with placebo.2 When ...

6.

ashpublications.org

ashpublications.org/blood/article/145/11/1126/534406/Efficacy-and-safety-of-venetoclax-plus-azacitidine

Efficacy and safety of venetoclax plus azacitidine for patients ...

Overall, venetoclax plus azacitidine at the RP2D was well tolerated and had favorable outcomes. A phase 3 study (NCT04401748) is ongoing to ...

7.

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.