Venetoclax + Azacitidine for Acute Myeloid Leukemia

(VIALE-T Trial)

No longer recruiting at 278 trial locations

Overseen By ABBVIE CALL CENTER

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: AbbVie

Disqualifiers: Other malignancy, HIV, Hepatitis, others

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how well a combination of two drugs, venetoclax and azacitidine, extends the lives of people with Acute Myeloid Leukemia (AML) after a stem cell transplant. Researchers aim to determine if this treatment is more effective than supportive care alone, which involves managing symptoms and complications. The trial consists of two parts: the first establishes the correct drug doses, and the second compares the combination treatment to supportive care alone. Suitable participants have AML and are either planning for or have recently undergone a stem cell transplant. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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 this trial's treatments are likely to be safe?

Research shows that the combination of venetoclax and azacitidine is generally well-tolerated by patients. Previous studies have found that most side effects can be managed. Common issues include low blood cell counts, nausea, and tiredness. Serious side effects can occur, but they are less common. These findings suggest that the treatment is reasonably safe for people with acute myeloid leukemia (AML).

Prospective trial participants should discuss potential risks and benefits with the research team. The team can provide more detailed information about what to expect based on these studies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of venetoclax and azacitidine for treating Acute Myeloid Leukemia (AML) because it targets cancer cells in a novel way. Venetoclax works by inhibiting a protein called BCL-2, which helps cancer cells survive. By blocking this protein, venetoclax can potentially trigger the death of these cancer cells. Meanwhile, azacitidine, a type of chemotherapy, disrupts the DNA of cancer cells, preventing them from multiplying. This dual approach may offer a more effective strategy compared to the standard chemotherapy options like cytarabine and daunorubicin, which primarily focus on killing fast-growing cells without the targeted action of venetoclax. Additionally, the inclusion of best supportive care ensures that patients receive comprehensive treatment tailored to their needs.

What evidence suggests that this trial's treatments could be effective for Acute Myeloid Leukemia?

Research has shown that using venetoclax with azacitidine can benefit people with acute myeloid leukemia (AML). In this trial, some participants will receive the combination of venetoclax and azacitidine, while others will receive best supportive care. Studies have found that this combination extends life compared to azacitidine alone. For instance, one study showed that people who took both drugs lived longer than those who did not. Another study with older AML patients found that adding venetoclax to azacitidine led to better outcomes. These findings suggest that using both drugs together could be more effective than using just one. ^{1 6 7 8 9}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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 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 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 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 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]

Citations

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

Outcomes of patients treated with venetoclax plus ... Measurable residual disease response and prognosis in treatment-naïve acute myeloid leukemia with venetoclax and azacitidine. J Clin Oncol ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12135334/

Efficacy and safety of venetoclax and azacitidine for acute ... The salvage therapy outcomes in patients with treatment-naïve AML after AZA-VEN suggested best outcomes for VEN-AZA combined with a targeted ...

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. 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. 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).

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, ...