Venetoclax + Azacitidine for Leukemia

Overseen By Derek Schatz

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Colorado, Denver

Must not be taking: CYP3A inhibitors, CYP3A inducers

Disqualifiers: HIV, Hepatitis B/C, Heart failure, 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: Unknown

Duration: 16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for adults with acute myeloid leukemia (AML) who have not yet received prior treatment. The focus is on combining two drugs, venetoclax (a targeted therapy) and azacitidine (a chemotherapy drug), to evaluate their effectiveness in treating this type of blood cancer. Participants will receive azacitidine intravenously for seven days, while the venetoclax dose will gradually increase from 100mg to 600mg. The trial seeks non-elderly adults diagnosed with AML who have not received any treatment for this condition. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take certain steroids or drugs that affect liver enzymes (CYP3A inhibitors or inducers) within 7 days before starting the study. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of venetoclax and azacitidine is generally well-tolerated by patients with acute myeloid leukemia (AML). In studies with older AML patients, this combination proved to be safe. Most patients managed the treatment well, though some experienced side effects like low white blood cell counts, nausea, and tiredness.

Previous research has also demonstrated that venetoclax, even when combined with other drugs, is usually safe and generally tolerated without major problems. These findings suggest that the treatment might be safe for those considering joining this clinical trial. However, discussing potential risks and benefits with a healthcare provider before deciding to participate is always important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Venetoclax combined with Azacitidine for leukemia because it offers a unique approach by targeting specific proteins that help cancer cells survive. Venetoclax works by inhibiting the BCL-2 protein, which is crucial for cancer cell survival, leading to their death. This is different from traditional chemotherapy, which attacks all rapidly dividing cells. Additionally, Azacitidine is administered intravenously, while Venetoclax is taken orally, offering a convenient combination that enhances patient comfort and adherence. This targeted strategy not only has the potential to improve effectiveness but also to reduce side effects compared to more generalized treatments.

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

Research has shown that combining venetoclax with azacitidine, the focus of this trial, may effectively treat acute myeloid leukemia (AML). One study found that this combination outperformed azacitidine alone, leading to better patient outcomes. Another study supported these findings, demonstrating effectiveness in patients who had not previously received treatment for AML. This suggests that venetoclax and azacitidine together could be a strong treatment option for individuals with this type of leukemia. ^{1 2 3 5 6}

Who Is on the Research Team?

Daniel Pollyea, MD

Principal Investigator

University of Colorado, Denver

Are You a Good Fit for This Trial?

Adults aged 18-59 with newly diagnosed acute myeloid leukemia (AML) who haven't been treated before can join. They should be in relatively good health, with an ECOG score of ≤2, and have normal liver and kidney function. Men must use contraception; women not post-menopausal or without a hysterectomy/oophorectomy must use two forms of birth control or abstain from sex.

Inclusion Criteria

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

I will use birth control from the start of the study drug until 90 days after the last dose.

I am a pre-menopausal woman who agrees to use two forms of birth control or abstain from sex.

Exclusion Criteria

I have been treated for MDS or AML, but ATRA for suspected APL doesn't disqualify me.

I cannot take medicine by mouth due to a digestive condition.

I am currently being treated for a serious infection that is not under control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive up to four cycles of venetoclax and azacitidine. Azacitidine is given intravenously for 7 days, and venetoclax is given orally, starting at 100mg and progressing to 600mg.

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including response rate and incidence of minimal residual disease.

4 years

Maintenance or Extension

Depending on recovery, participants may continue medication, receive maintenance therapy, or pursue an allogeneic stem cell transplant.

What Are the Treatments Tested in This Trial?

Interventions

• Azacitidine
• Venetoclax

Trial Overview The trial is testing the combination of two drugs, Venetoclax and Azacitidine, as a treatment for AML in non-elderly adults. It's aimed at those who are newly diagnosed and have not received any prior treatments for their condition.

How Is the Trial Designed?

Group I: Azacitidine and Venetoclax Experimental Treatment 2 Interventions

Azacitidine will be given intravenously for 7 days. Venetoclax will be given orally. The patient will start out with 100mg and progress to 600mg. Once 600mg is reached, the patient will stay at this dose until the 28 day cycle is finished.

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?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

AbbVie

Industry 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 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 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 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/PMC10928973/

Meta‑analysis of the efficacy of venetoclax and azacitidine ... The combination of venetoclax and azacitidine demonstrated greater overall efficacy than azacitidine monotherapy for AML treatment.

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

Azacitidine and Venetoclax in Previously Untreated Acute ... In March 2020, the trial was declared to be successful (i.e., the trial showed efficacy of azacitidine plus venetoclax as compared with the ...

3. 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 ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0006497118473065

A Phase 1b Study of Venetoclax (ABT-199/GDC-0199) in ... A Phase 1b Study of Venetoclax (ABT-199/GDC-0199) in Combination with Decitabine or Azacitidine in Treatment-Naive Patients with Acute Myelogenous Leukemia

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

Evaluating venetoclax and its potential in treatment-naïve ... Initial clinical trials examined venetoclax's efficacy in CLL. Tumor lysis was a major concern during these early trials; the first Phase I study utilized a ...

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) ...