Venetoclax + Azacitidine for Myelodysplastic Syndrome

Not currently recruiting at 70 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: AbbVie

Must not be taking: BH3 mimetics

Disqualifiers: Low-risk MDS, t-MDS, MDS/MPN, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, venetoclax and azacitidine, to determine their effectiveness for people with myelodysplastic syndrome (MDS). The study focuses on patients who have not received prior treatment and are considered higher-risk based on specific scoring systems that assess the severity of their condition. Suitable candidates for this trial are those who have never been treated for MDS and have been diagnosed with the higher-risk type. The study aims to identify a safe and effective dose and evaluate how well these drugs work together. As a Phase 1 trial, the research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it does mention that prior therapy for MDS is not allowed, so it's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Studies have shown that the combination of venetoclax and azacitidine is generally well-tolerated. Research indicates that patients treated with this combination experience higher remission rates compared to those receiving azacitidine alone. While some side effects occur, they are usually manageable. Common issues include nausea and low blood cell counts, but serious side effects are rare. As this is a Phase 1 trial, the main goal is to ensure safety and determine the correct dose, so participants receive close monitoring for any problems. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the combination of Venetoclax and Azacitidine for treating Myelodysplastic Syndrome because it offers a new approach. Most treatments for this condition, like chemotherapy, mainly target rapidly dividing cells, which can affect both cancerous and healthy cells. However, Venetoclax works differently by targeting and inhibiting the BCL-2 protein, which helps cancer cells survive. This targeted action, combined with Azacitidine, which can help boost the effect of Venetoclax, could potentially lead to more effective treatment with fewer side effects. This combination aims to strike at the root of the cancer cells' survival mechanism, offering hope for better outcomes.

What evidence suggests that this trial's treatments could be effective for myelodysplastic syndrome?

Research has shown that using venetoclax with azacitidine, the combination studied in this trial, may help treat high-risk myelodysplastic syndrome (MDS). Studies have found that this combination increases the chances of remission more than azacitidine alone. In patients with acute myeloid leukemia (AML), which is similar to MDS, this combination has also increased remission rates. Another study confirmed that this treatment works better for both AML and MDS than azacitidine alone. Overall, early findings suggest this treatment could be more effective for patients with higher-risk MDS. ^{2 4 6 7 8}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed higher-risk Myelodysplastic Syndromes (MDS) who haven't been treated before. They should have a certain level of risk based on scoring systems like IPSS or IPSS-R and less than 20% bone marrow blasts. Participants need to be fairly active and able to care for themselves (ECOG score ≤2). Those who've had previous MDS treatments, live vaccines recently, other types of MDS, or any organ transplants can't join.

Inclusion Criteria

I can take care of myself and am up and about more than half of my waking hours.

I have a specific type of blood disorder (MDS) that is serious but not yet treated, and my bone marrow is mostly healthy.

Exclusion Criteria

My condition is a type of MDS not treated before, with a low to intermediate risk score, or it has evolved from another blood disorder.

I have received treatment for myelodysplastic syndrome (MDS) before.

I have had a stem cell or organ transplant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive venetoclax in combination with azacitidine to determine the recommended Phase 2 dose

Up to 32 days

Safety Expansion

Participants continue to receive the determined dose to further evaluate safety and pharmacokinetics

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years after the last participant is enrolled

What Are the Treatments Tested in This Trial?

Interventions

• Azacitidine
• Venetoclax

Trial Overview The study tests Venetoclax combined with Azacitidine in people with high-risk MDS who haven’t received treatment yet. It's an early-phase trial that includes finding the right dose and checking how safe it is over time.

How Is the Trial Designed?

Group I: Venetoclax + Azacitidine Experimental Treatment 2 Interventions

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

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

Published Research Related to This Trial

In a phase 1b study involving 44 patients with relapsed/refractory higher-risk myelodysplastic syndromes (MDS), the combination of venetoclax and azacitidine demonstrated significant activity, with a median overall survival of 12.6 months after prior treatment failure with hypomethylating agents.

The treatment resulted in hematological improvements, including complete remission in 7% of patients and transfusion independence in 36%, indicating that venetoclax plus azacitidine can provide meaningful clinical benefits for patients with limited options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1b study of venetoclax and azacitidine combination in patients with relapsed or refractory myelodysplastic syndromes. Zeidan, AM., Borate, U., Pollyea, DA., 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 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 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 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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10100228/

A phase 1b study of venetoclax and azacitidine ... Poor outcome of patients with myelodysplastic syndrome after azacitidine treatment failure. Clin Lymphoma Myeloma Leuk. 2013;13(6):711‐715. [DOI] [PubMed] ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04160052

Venetoclax and Azacitidine for the Treatment of High-Risk ... This phase I/II trial studies the side effects and best dose of venetoclax when given together with azacitidine in treating patients with high-risk ...

3. tandfonline.com tandfonline.com/doi/full/10.1080/16078454.2023.2198098

Full article: The efficacy and safety of venetoclax and ... The present meta-analysis demonstrated that the Ven + AZA regimen is efficacious for the treatment of AML and MDS, with it being more effective for ND-AML than ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa2012971

Azacitidine and Venetoclax in Previously Untreated Acute ... The incidence of remission was higher among patients who received azacitidine plus venetoclax than among those who received azacitidine alone.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04401748

NCT04401748 | Study Of Venetoclax Tablet With ... The purpose of this study is to see how safe and effective venetoclax and azacitidine (AZA) combination are when compared to AZA and a placebo (contains no ...

6. 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) ...

7. 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 ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6499443/

Evaluating venetoclax and its potential in treatment-naïve ... Study of ABT-199 (GDC-0199) in combination with azacitidine or decitabine (chemo combo) in subjects with AML, Active, not recruiting, AML, Venetoclax,