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

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

50 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well azacitidine and venetoclax work in treating patients with acute myeloid leukemia that is in remission. Drugs used in chemotherapy, such as azacitidine and venetoclax, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

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.

What data supports the idea that Azacitidine + Venetoclax for Acute Myeloid Leukemia is an effective drug?

The available research shows that the combination of Azacitidine and Venetoclax is effective for treating Acute Myeloid Leukemia, especially in older patients or those who cannot undergo intensive chemotherapy. One study found that this combination improved remission rates and survival compared to Azacitidine alone. Another study reported that patients receiving this combination had a significant increase in overall survival compared to those receiving a placebo with Azacitidine. Additionally, in a study conducted in Latin America, patients with newly diagnosed Acute Myeloid Leukemia had a high response rate, with 78.6% showing improvement, and a median survival of 9.6 months. These findings suggest that Azacitidine and Venetoclax together are a promising option for treating this condition. ^{1 2 3 4 5}

What data supports the effectiveness of the drug combination Azacitidine and Venetoclax for treating acute myeloid leukemia?

Research shows that the combination of Azacitidine and Venetoclax improves remission rates and survival in older or unfit patients with acute myeloid leukemia compared to Azacitidine alone. Additionally, a study in Latin America found that this drug combination had favorable response rates and survival outcomes in both newly diagnosed and relapsed patients. ^{1 2 3 4 5}

What safety data is available for Azacitidine and Venetoclax in treating Acute Myeloid Leukemia?

The safety of Azacitidine and Venetoclax (Ven+AZA) in treating Acute Myeloid Leukemia (AML) has been evaluated in several studies. Common hematologic toxicities were reported, but the treatment was generally tolerable. In a study conducted in Latin America, hematologic toxicities were common, but the treatment was effective with a complete response rate of 78.6% in newly diagnosed patients. Another study in China found that Ven+AZA was tolerable for AML patients, with a high response rate and some achieving minimal residual disease negativity. The treatment was effective in patients with specific genetic mutations like NPM1, IDH1/IDH2, and TP53. Overall, the safety profile is considered acceptable, but long-term efficacy and safety remain to be observed. ^{1 3 5 6 7}

Is the combination of Azacitidine and Venetoclax safe for treating acute myeloid leukemia?

The combination of Azacitidine and Venetoclax has been studied for safety in patients with acute myeloid leukemia. Common side effects include blood-related issues, but the treatment is generally considered tolerable for patients who cannot undergo standard chemotherapy. ^{1 3 5 6 7}

Is the drug combination of Azacitidine and Venetoclax a promising treatment for Acute Myeloid Leukemia?

Yes, the combination of Azacitidine and Venetoclax is promising for treating Acute Myeloid Leukemia, especially in older patients or those who cannot undergo intensive chemotherapy. It improves remission rates and survival compared to using Azacitidine alone. ^{1 2 3 4 8}

How is the drug combination of Azacitidine and Venetoclax unique for treating acute myeloid leukemia?

The combination of Azacitidine and Venetoclax is unique because it is specifically used for older patients or those who cannot undergo intensive chemotherapy, improving remission rates and survival compared to Azacitidine alone. This combination is particularly beneficial for patients who are newly diagnosed and considered unfit for standard intensive treatments. ^{1 2 3 4 8}

Research Team

Tapan Kadia, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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 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 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]

References

1. Switzerland 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. [2023]

2. United States 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. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Venetoclax in combination with azacitidine in Japanese patients with acute myeloid leukaemia: phase 1 trial findings. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Venetoclax plus azacitidine in Japanese patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Venetoclax-based combinations for acute myeloid leukemia: optimizing their use in Latin-America. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Single-institution experience of venetoclax combined with azacitidine in newly diagnosed acute myeloid leukemia patients. [2023]

7. China pubmed.ncbi.nlm.nih.gov

[Short-term efficacy of venetoclax combined with azacitidine in acute myeloid leukemia: a single-institution experience]. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

TP53 or Not TP53: That Is the Question. [2023]