Venetoclax + Azacitidine for Acute Myeloid Leukemia

(VIALE-T Trial)

Recruiting at 248 trial locations

Overseen By ABBVIE CALL CENTER

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: AbbVie

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

465 Participants Needed

Trial Summary

What is the purpose of this trial?

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 Leukemia (AML) participants compared to Best Supportive Care (BSC) when given as maintenance therapy following allogeneic stem cell transplantation (SCT). This study will have 2 parts: Part 1 (Dose Confirmation), which may include participants who are greater than or equal to 18 years old; Part 2 (Randomization) which may include participants who are greater than or equal to 12 years old. During Part 1, recommended Phase 3 dose of venetoclax in combination with azacitidine will be determined and during Part 2, the efficacy and safety of venetoclax with azacitidine (Part 2 Arm A) will be compared with BSC (Part 2 Arm B).

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 effectiveness of the drug combination Venetoclax and Azacitidine for treating Acute Myeloid Leukemia?

Research shows that the combination of venetoclax and azacitidine improves remission rates and survival in older or unfit patients with acute myeloid leukemia compared to azacitidine alone. Additionally, the VIALE-A trial found that this combination significantly prolonged overall survival in patients who were not eligible for intensive chemotherapy. ^{1 2 3 4 5}

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

The combination of Venetoclax and Azacitidine has been studied for safety in patients with acute myeloid leukemia, showing common blood-related side effects. These studies suggest it is generally safe for use in humans, but patients may experience some blood-related toxicities. ^{2 3 6 7 8}

How is the drug Venetoclax + Azacitidine unique for treating acute myeloid leukemia?

Venetoclax combined with azacitidine is unique because it is specifically used for older patients or those who cannot undergo standard chemotherapy, offering improved remission rates and survival compared to azacitidine alone. This combination is particularly beneficial for patients who are newly diagnosed and considered unfit for more aggressive treatments. ^{1 3 6 7 9}

Research Team

ABBVIE INC.

Principal Investigator

AbbVie

Eligibility Criteria

This trial is for AML patients who are at least 18 years old for Part 1 and at least 12 for Part 2, have had or are planning an allogeneic stem cell transplant, and meet specific health criteria. It's not open to those with certain infections, a history of other cancers within the last two years (with some exceptions), or disease progression on venetoclax before.

Inclusion Criteria

My kidney, liver, and blood tests meet the study's requirements.

I have AML and am planning or have had a stem cell transplant within 45 days.

I am over 17 with a KPS score above 50, or 12-16 years old with a Lansky score above 40.

Exclusion Criteria

I show signs of a blood cancer that has spread outside my bone marrow.

I haven't had cancer, except for certain skin cancers or treated early-stage cancers, in the last 2 years.

I have HIV or have had hepatitis B or C.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Confirmation

Participants receive various doses of venetoclax and azacitidine to determine the recommended Phase 3 dose

28 days

Daily administration

Randomization and Treatment

Participants are randomized to receive venetoclax with azacitidine or best supportive care

Up to 24 cycles (each cycle = 28 days)

Daily administration for venetoclax, Days 1-5 for azacitidine per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 39 months after randomization

Treatment Details

Interventions

• Azacitidine
• Venetoclax

Trial Overview The study tests if Venetoclax combined with Azacitidine improves survival in AML patients after stem cell transplantation compared to just supportive care. The first part determines the best dose; the second part compares effectiveness and safety between the two approaches.

Participant Groups

Group I: Part 2: Arm B - Best Supportive Care (BSC) Experimental Treatment 1 Intervention

Participants will receive treatment as prescribed by their physician according to the BSC for up to 24 cycles (1 cycle = 28 days)

Group II: Part 2: Arm A - Venetoclax + Azacitidine (AZA) + BSC Experimental Treatment 3 Interventions

Participants will be administered with venetoclax and AZA at a dose level determined in Part 1 in addition to best supportive care (when required). Venetoclax will be administered once daily (QD) (Days 1-28) for up to 24 cycles, AZA QD on Days 1-5 of each 28-day cycle for up to 6 cycles and best supportive care (BSC) for 24 cycles (each cycle = 28 days).

Group III: Part 1: Venetoclax + Azacitidine (AZA) + Best Supportive Care Experimental Treatment 3 Interventions

Participants will be administered various doses and dose regiments of venetoclax and AZA. Venetoclax will be administered once daily (QD) (Days 1-28) for up to 24 cycles, AZA QD on Days 1-5 of each 28-day cycle for up to 6 cycles and best supportive care (BSC) for 24 cycles (each cycle = 28 days)

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?

AbbVie

Lead 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

Findings from Research

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 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 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 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 treatment-naïve patients with IDH1/2-mutant acute myeloid leukemia (AML), the combination of venetoclax and azacitidine resulted in a high composite complete remission rate of 79% and a median overall survival of 24.5 months, significantly outperforming the azacitidine-only group, which had an 11% remission rate and 6.2 months of survival.

The treatment was found to be safe, with no unexpected toxicities reported, and the favorable outcomes for patients with IDH1/2 mutations were consistent regardless of their cytogenetic risk, indicating a robust efficacy of this regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Venetoclax and Azacitidine in Treatment-Naïve Patients with Acute Myeloid Leukemia and IDH1/2 Mutations. Pollyea, DA., DiNardo, CD., Arellano, ML., 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 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 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 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]

References

1. 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]

2. England pubmed.ncbi.nlm.nih.gov

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

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

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

4. United States 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. [2023]

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

Impact of Venetoclax and Azacitidine in Treatment-Naïve Patients with Acute Myeloid Leukemia and IDH1/2 Mutations. [2023]

6. England pubmed.ncbi.nlm.nih.gov

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

7. Netherlands pubmed.ncbi.nlm.nih.gov

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

8. England pubmed.ncbi.nlm.nih.gov

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

9. 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]