Venetoclax + Azacitidine for Acute Myeloid Leukemia

Overseen By Betul Oran

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immune suppressives

Disqualifiers: Active GVHD, Infections, Cardiac 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: 72

Duration: 48-96 weeks

125 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments, venetoclax and azacitidine, to determine their effectiveness in controlling acute myeloid leukemia (AML) after a stem cell transplant. Venetoclax blocks a protein essential for cancer cell survival, while azacitidine is a chemotherapy drug that stops cancer cells from growing or spreading. The goal is to prevent high-risk leukemia from returning post-transplant. The trial seeks participants who have undergone a stem cell transplant and are currently in remission from AML or certain other blood cancers. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, it mentions that participants should not have uncontrolled infections or be on certain immune suppressive drugs, so it's best to discuss your specific medications with the trial team.

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

Research has shown that the combination of venetoclax and azacitidine is generally well-tolerated by people with acute myeloid leukemia (AML). In studies, many patients experienced side effects, but these were mostly manageable. Common side effects included low blood cell counts, nausea, and diarrhea. Serious side effects occurred less frequently, and doctors closely monitored patients to manage these risks.

Venetoclax, used in other treatments, works by blocking a protein that helps cancer cells survive. Azacitidine, a long-standing chemotherapy agent, stops cancer cells from growing or spreading. Both have shown promise in controlling leukemia.

Overall, the combination appears relatively safe, but participants should discuss any concerns with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments for acute myeloid leukemia?

Researchers are excited about using venetoclax and azacitidine for treating acute myeloid leukemia (AML) because they target cancer cells in innovative ways. Unlike standard treatments like chemotherapy, which attacks rapidly dividing cells broadly, venetoclax specifically targets and inhibits the BCL-2 protein that helps cancer cells survive. This targeted approach can potentially lead to fewer side effects and improve the quality of life for patients. Additionally, when combined with azacitidine, which modifies DNA to reactivate tumor suppressor genes, this treatment duo can be more effective in eradicating residual leukemia cells and preventing relapse after stem cell transplantation.

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

Studies have shown that using venetoclax with azacitidine can effectively treat acute myeloid leukemia (AML), particularly for patients unable to undergo intensive chemotherapy. Research indicates that this combination can extend the lives of older patients with AML. One study found that patients receiving both venetoclax and azacitidine lived longer than those receiving only azacitidine. In this trial, participants will receive the combination of venetoclax and azacitidine. This treatment works in two ways: venetoclax blocks a protein essential for cancer cell survival, and azacitidine prevents cancer cells from growing and spreading. Overall, this treatment shows promise in controlling high-risk leukemia and preventing its recurrence after a stem cell transplant. ^{1 6 7 8 9}

Who Is on the Research Team?

Betul Oran, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with acute myeloid leukemia who are in remission after a stem cell transplant but have high-risk features like minimal residual disease. They should be within 42 to 100 days post-transplant, have good organ function, and no active graft-versus-host disease or other serious conditions.

Inclusion Criteria

I understand the study's risks and benefits and can consent.

My kidney function is within the required range.

My AML is classified as high-risk based on specific genetic features.

Exclusion Criteria

I have been cancer-free for over a year, except for leukemia.

I have been diagnosed with a type of skin cancer.

I have uncontrolled graft-versus-host disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive venetoclax and azacitidine for maintenance or minimal residual disease after allogeneic stem cell transplantation. Treatment repeats every 4-8 weeks for up to 12 cycles.

48-96 weeks

12 cycles of treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment, including incidence of severe infections and other adverse events.

8 weeks

Follow-up visits up to 60 days after last V+V dose

What Are the Treatments Tested in This Trial?

Interventions

• Azacitidine
• Venetoclax

Trial Overview The effectiveness of venetoclax combined with azacitidine is being tested as a treatment to prevent the return of acute myeloid leukemia after stem cell transplantation. Venetoclax targets proteins that cancer cells need to survive, while azacitidine interferes with their growth.

How Is the Trial Designed?

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

Patients receiving venetoclax and azacitidine for maintenance after allogeneic stem cell transplantation, receive azacitidine SC on days 1-5 and venetoclax PO QD on days 1-7. Patients receiving venetoclax and azacitidine for minimal residual disease after allogeneic stem cell transplant, receive azacitidine SC on days 1-5 and venetoclax PO QD on days 1-14. Treatment repeats every 4-8 weeks for up to 12 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+

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 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 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 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 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 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]

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. 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.

3. 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 ...

4. 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.

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. 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/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 ...

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, ...