Venetoclax + Cytarabine for Acute Myeloid Leukemia

No longer recruiting at 142 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AbbVie

Must not be taking: Antiretrovirals, CYP3A inducers

Disqualifiers: HIV, Hepatitis B/C, CNS involvement, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 17.1 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether the drug venetoclax, combined with low-dose cytarabine (a chemotherapy drug), can extend the lives of people with acute myeloid leukemia (AML) compared to cytarabine with a placebo. It targets individuals who have not yet received treatment for AML. Suitable candidates include those diagnosed with AML who cannot undergo intensive chemotherapy, possibly due to existing health conditions like heart or lung issues. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

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 have received prior treatment for AML, except for hydroxyurea. Also, you should not take strong or moderate CYP3A inducers 7 days before starting the study treatment.

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

Studies have shown that venetoclax, when combined with low-dose cytarabine (LDAC), is generally well-tolerated in patients with acute myeloid leukemia (AML). Research indicates that this combination effectively targets and kills cancer cells. Patients taking venetoclax and LDAC together often did not experience severe side effects, though some reported mild issues such as nausea and low blood cell counts. These are common side effects of many cancer treatments. Overall, the safety profile appears manageable, allowing many patients to continue their daily activities. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for AML?

Researchers are excited about venetoclax plus low-dose cytarabine for treating acute myeloid leukemia (AML) because this combination targets cancer cells differently than standard treatments. Most AML treatments rely on high-dose chemotherapy, which can be harsh and cause significant side effects. Venetoclax works by inhibiting a protein called BCL-2, which helps cancer cells survive. This mechanism makes it potentially effective when combined with low-dose cytarabine, offering a less intensive option that could be easier on patients while still targeting the leukemia cells effectively.

What evidence suggests that venetoclax + cytarabine could be an effective treatment for acute myeloid leukemia?

Research has shown that venetoclax, when combined with low-dose cytarabine, may benefit people with acute myeloid leukemia (AML) who cannot undergo strong chemotherapy. In this trial, one group of participants will receive this combination. Venetoclax targets proteins that help cancer cells survive. By blocking these proteins, venetoclax facilitates chemotherapy in killing cancer cells. Studies have found that using venetoclax with other drugs effectively treats AML. This combination could offer a promising option for those needing a gentler treatment approach. ^{6 7 8 9 10}

Who Is on the Research Team?

AbbVie Inc.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

This trial is for treatment-naive patients with acute myeloid leukemia who are unfit for intensive chemotherapy. They must be aged ≥75 or 18-74 with certain health conditions, have an ECOG performance status of 0-3, adequate liver and kidney function, a life expectancy of at least 12 weeks, and agree to contraception if applicable. Exclusions include prior malignancies (with some exceptions), known CNS involvement by AML, active hepatitis B/C infections, HIV infection.

Inclusion Criteria

My kidneys work well enough, with a creatinine clearance rate of at least 30 mL/min.

I am under 75 and my bilirubin levels are within the normal range.

My condition is not due to leukemia affecting my organs.

Exclusion Criteria

I have AML and may have been treated with hydroxyurea or for myelodysplastic syndrome, but not with cytarabine.

I have been diagnosed with acute promyelocytic leukemia.

I am HIV positive and aware of potential medication interactions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive venetoclax or placebo with low-dose cytarabine in 28-day cycles

Up to 17.1 months

Monthly visits for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 month

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Cytarabine
• Placebo
• Venetoclax

Trial Overview The study aims to determine if venetoclax combined with low-dose cytarabine improves survival compared to low-dose cytarabine and placebo in elderly or less fit patients with AML. Participants will either receive the combination therapy or the standard care (cytarabine plus placebo) to assess effectiveness.

How Is the Trial Designed?

Group I: Venetoclax + Low Dose Cytarabine (LDAC) Experimental Treatment 2 Interventions

Venetoclax 600 mg orally every day (QD) plus LDAC 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.

Group II: Placebo + LDAC Placebo Group 2 Interventions

Matching placebo to venetoclax orally QD plus LDAC 20 mg/m² subcutaneously on Days 1 to 10 of each 28-day cycle.

Cytarabine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Cytosar-U for:

• Acute myeloid leukemia
• Acute lymphocytic leukemia
• Chronic myeloid leukemia
• Meningeal leukemia

Approved in European Union as Depocyt for:

• Lymphomatous meningitis

Approved in Canada as Cytosar-U for:

• Acute myeloid leukemia
• Acute lymphocytic leukemia
• Chronic 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 Phase 3 clinical trial, venetoclax combined with low-dose cytarabine showed improved response rates and overall survival in patients with newly diagnosed acute myeloid leukemia who couldn't undergo intensive chemotherapy, supporting its efficacy.

In an expanded access study in Japan involving 14 patients, the safety profile of venetoclax was consistent with previous findings, with neutropenia being the most common serious side effect, indicating that careful management of adverse events is crucial in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax plus low-dose cytarabine in patients with newly diagnosed acute myeloid leukemia ineligible for intensive chemotherapy: an expanded access study in Japan. Asada, N., Ando, J., Takada, S., et al.[2023]

The combination of venetoclax with hypomethylating agents (HMA) has significantly improved survival rates in patients with acute myeloid leukemia (AML), as demonstrated in a phase 3 study.

Venetoclax is also safe when added to standard intensive regimens, leading to high remission rates and measurable residual disease negativity in both newly diagnosed and relapsed/refractory AML patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax in combination with nucleoside analogs in acute myelogenous leukemia. Ball, BJ., Koller, PB., Pullarkat, V.[2023]

Venetoclax, when combined with hypomethylating agents or low-dose cytarabine, has shown remarkable effectiveness in treating newly diagnosed acute myeloid leukemia (AML) in elderly and unfit patients, with a favorable safety profile and low early treatment-related mortality.

Due to its success in older patients, venetoclax is now being explored as a frontline treatment for younger patients with AML and those with relapsed or refractory cases, indicating its potential to change AML treatment across different age groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax-containing regimens in acute myeloid leukemia. Aldoss, I., Pullarkat, V., Stein, AS.[2021]

In a subgroup of 27 Japanese patients with newly diagnosed acute myeloid leukaemia, venetoclax combined with low-dose cytarabine showed a higher complete remission rate (44.4%) compared to placebo (11.1%), indicating potential efficacy in this population.

Despite the higher remission rate, the median overall survival was similar between the venetoclax (4.7 months) and placebo (8.1 months) groups, suggesting limited survival benefit, which may be influenced by small sample size and baseline health differences among patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax plus low-dose cytarabine in Japanese patients with untreated acute myeloid leukaemia ineligible for intensive chemotherapy. Yamauchi, T., Yoshida, C., Usuki, K., et al.[2022]

In a study of 211 patients with untreated acute myeloid leukemia (AML) who were not eligible for intensive chemotherapy, venetoclax combined with low-dose cytarabine (LDAC) showed a median overall survival of 8.4 months compared to 4.1 months for the placebo group, indicating a 30% reduction in the risk of death.

The treatment with venetoclax + LDAC also resulted in significantly higher complete response rates (48.3% vs. 13.2%) and improved event-free survival (4.9 months vs. 2.1 months), while maintaining a similar safety profile to the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

6-month follow-up of VIALE-C demonstrates improved and durable efficacy in patients with untreated AML ineligible for intensive chemotherapy (141/150). Wei, AH., Panayiotidis, P., Montesinos, P., et al.[2022]

In a study of 86 patients with relapsed or refractory acute myeloid leukemia (RR-AML) treated with venetoclax combinations, the complete remission rate was 24%, and the overall response rate was 31%, indicating that venetoclax is an effective treatment option for this patient group.

Azacitidine combined with venetoclax showed significantly better outcomes than low-dose cytarabine with venetoclax, with median overall survival of 25 months compared to 3.9 months, highlighting the importance of treatment choice in improving survival in RR-AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and molecular predictors of response and survival following venetoclax therapy in relapsed/refractory AML. Stahl, M., Menghrajani, K., Derkach, A., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6524989/

Venetoclax Combined With Low-Dose Cytarabine for ... Effective treatment options are limited for patients with acute myeloid leukemia (AML) who cannot tolerate intensive chemotherapy.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03941964

NCT03941964 | A Study of the Effectiveness of Venetoclax ... A study evaluating the effectiveness and safety of venetoclax, in combination with azacitidine or decitabine, in an outpatient setting for treatment-naïve ...

3. eurjmedres.biomedcentral.com eurjmedres.biomedcentral.com/articles/10.1186/s40001-025-02571-x

Meta-analysis on the effectiveness and safety of venetoclax ... This meta-analysis focuses on evaluating the efficacy and adverse reactions of venetoclax in combination with HMAs in AML treatment.

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

Evaluating venetoclax and its potential in treatment-naïve ... Venetoclax (ABT-199), a BH3-mimetic and selective BCL-2 inhibitor, was recently approved by the US Food and Drug Administration (FDA) for the treatment of acute ...

5. ashpublications.org ashpublications.org/bloodadvances/article/8/13/3583/516002/Venetoclax-a-new-player-in-the-treatment-of

Venetoclax: a new player in the treatment of children with high ... After its first clinical application in chronic lymphocytic leukemia,3 venetoclax has shown efficacy in acute myeloid leukemia (AML) models.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8225137/

Review of Venetoclax in CLL, AML and Multiple Myeloma Venetoclax is a highly selective and effective B-cell lymphoma-2 (BCL-2) inhibitor, which is able to reinstate the apoptotic potential of cancer cells.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06504459

Study Details | NCT06504459 | Venetoclax in Combination ... Giving venetoclax with cladribine and cytarabine alternating with azacitidine and venetoclax may kill more cancer cells in patients with newly diagnosed ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04029688

NCT04029688 | A Study Evaluating the Safety, Tolerability ... This is a Phase I/II, multicenter, open-label, multi-arm study designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9318140/

Targeting Acute Myeloid Leukemia with Venetoclax Venetoclax is a BCL-2 inhibitor that effectively improves clinical outcomes in newly diagnosed, relapsed and refractory acute myeloid leukemia (AML) patients, ...

10. sciencedirect.com sciencedirect.com/science/article/pii/S0301472X18300420

Review Venetoclax: A new wave in hematooncology Venetoclax has synergic activity with low-dose cytarabine, 5-azacytidine (5-Aza) in acute myeloid leukemia. Inhibitors of antiapoptotic proteins of the BCL2 ...