Venetoclax + Chemotherapy for Acute Myeloid Leukemia

(Venetoclax AML Trial)

Recruiting at 2 trial locations

Overseen By Ioannis Mantzaris, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Ioannis Mantzaris

Disqualifiers: Heart failure, Myocardial infarction, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

99 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for people with acute myeloid leukemia (AML), a type of blood cancer. Researchers aim to determine the safest and most effective dose of Venetoclax, a targeted therapy, when combined with standard chemotherapy drugs. People newly diagnosed with AML or certain similar conditions, who haven't received prior treatment, might be suitable candidates. The trial seeks to evaluate the effectiveness and safety of this combination for patients. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

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

Research has shown that venetoclax, when combined with other treatments, is generally safe for patients with acute myeloid leukemia (AML), though it carries some risks. One study found that venetoclax can increase the risk of severe neutropenia, a condition where dangerously low white blood cell counts make patients more susceptible to infections.

Cytarabine has long been used to treat AML and is usually safe. It is well-tolerated even by older patients, with rare instances of neurotoxicity, which involves damage to the nervous system.

Daunorubicin, another chemotherapy drug in this trial, also has a good safety record. Studies have shown it is safe in both higher and lower doses for newly diagnosed AML patients.

When used together, as previous studies have indicated, these drugs are considered safe for helping AML patients achieve remission. However, careful monitoring remains crucial due to the potential for serious side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for acute myeloid leukemia?

Researchers are excited about Venetoclax in combination with chemotherapy for treating Acute Myeloid Leukemia (AML) because it introduces a novel mechanism by targeting cancer cells' ability to regulate apoptosis, or programmed cell death. Unlike standard treatments like the "7+3" regimen of Cytarabine and Daunorubicin, Venetoclax specifically inhibits the BCL-2 protein, which helps cancer cells survive. This targeted approach can potentially enhance the effectiveness of traditional chemotherapy, offering a promising new strategy to improve outcomes for patients with AML.

What evidence suggests that Venetoclax plus chemotherapy could be effective for acute myeloid leukemia?

Research has shown that venetoclax, when combined with the 7+3 chemotherapy regimen, may help treat acute myeloid leukemia (AML). Studies have found that this combination can lead to cancer remission in about 72% of patients. On average, patients live approximately 11 months after starting this treatment. The risk of dying within the first eight weeks is relatively low at 6%. These findings suggest the treatment might offer a good chance of remission, although results can vary for each person. ^{6 7 8 9 10}

Who Is on the Research Team?

Ioannis Mantzaris, MD

Principal Investigator

Montefiore Medical Center

Are You a Good Fit for This Trial?

Adults aged 18-75 with a new diagnosis of acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS), who may have had prior treatments at the investigator's discretion. Participants must be in good physical condition (ECOG ≤2), have proper kidney and liver function, and agree to use contraception. Excluded are those with certain heart conditions, active CNS AML involvement, uncontrolled infections like HIV/Hepatitis B/C, gastrointestinal absorption issues, significant medical/psychiatric history affecting study participation, extremely high white cell count or women not using effective birth control.

Inclusion Criteria

Ability to understand and provide signed informed consent

I have been newly diagnosed with AML according to WHO standards.

I can take care of myself but might not be able to do heavy physical work.

Exclusion Criteria

My leukemia is of a specific type known as acute promyelocytic.

My acute myeloid leukemia has spread to my brain or spinal cord.

My white blood cell count is above 25 x 10⁹/L.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Participants receive Venetoclax in combination with daunorubicin and cytarabine to determine the maximum tolerated dose

Up to 6 weeks

Multiple visits for dose escalation and monitoring

Consolidation Treatment

Participants who achieve CRc proceed to consolidation therapy with high-dose cytarabine and Venetoclax

Up to 42 days per cycle, for up to 4 cycles

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 6 years

What Are the Treatments Tested in This Trial?

Interventions

• Cytarabine
• Daunorubicin
• Venetoclax

Trial Overview

The trial is testing Venetoclax combined with intensive chemotherapy drugs Daunorubicin and Cytarabine in untreated adults with AML/MDS. It has two parts: first determining the safest dose combination (dose escalation), then expanding to more patients to compare this optimal dose against the starting dose for safety and effectiveness (dose expansion).

How Is the Trial Designed?

Group I: Venetoclax plus 7+3 Experimental Treatment 3 Interventions

see detailed description

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?

Ioannis Mantzaris

Lead Sponsor

Trials

1

Recruited

100+

Montefiore Medical Center

Lead Sponsor

Trials

468

Recruited

599,000+

Dana-Farber Cancer Institute

Collaborator

Trials

1,128

Recruited

382,000+

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

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 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]

In a phase 2 clinical trial involving 42 adults with newly diagnosed acute myeloid leukemia (AML), the combination of venetoclax with daunorubicin and cytarabine (DA 2 + 6) achieved a high overall response rate of 92.9%, indicating strong efficacy in treating this condition.

The treatment demonstrated a shorter myelosuppressive period compared to previous regimens, with median recovery times for neutrophils and platelets of 13 and 12 days, respectively, while maintaining similar efficacy and safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax combined with daunorubicin and cytarabine (2 + 6) as induction treatment in adults with newly diagnosed acute myeloid leukemia: a phase 2, multicenter, single-arm trial. Suo, X., Zheng, F., Wang, D., 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]

In a phase 2 trial involving 33 adults with newly diagnosed acute myeloid leukaemia, the combination of venetoclax with daunorubicin and cytarabine (DAV regimen) achieved a remarkable composite complete remission rate of 91% after one cycle of treatment.

The treatment was found to be safe, with no treatment-related deaths reported, although all patients experienced grade 3 or worse adverse events, such as neutropenia and thrombocytopenia, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax plus 3 + 7 daunorubicin and cytarabine chemotherapy as first-line treatment for adults with acute myeloid leukaemia: a multicentre, single-arm, phase 2 trial. Wang, H., Mao, L., Yang, M., et al.[2022]

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]

Citations

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Efficacy and Biological Correlates of Response in a Phase II ...

A and B, the median leukemia-free survival was 2.3 months (range, 1.0–2.7), and the median overall survival was 4.7 months (range, 2.3–6.0), in patients with ...

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pmc.ncbi.nlm.nih.gov

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

Evaluating venetoclax and its potential in treatment-naïve ...

Results were dramatic–venetoclax plus rituximab achieved an 84.9% progression-free survival rate at 2 years, vs the bendamustine plus rituximab arm, which ...

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clinicaltrials.gov

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NCT01994837 | A Phase 2 Study of ABT-199 in Subjects ...

This was a Phase 2, open-label, multicenter study evaluating the preliminary efficacy and safety of venetoclax (ABT-199) administered orally in participants ...

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Meta-analysis on the effectiveness and safety of venetoclax ...

This approach has yielded a long-term cure rate of 30% to 40% in young AML patients [1, 15,16,17,18]. Despite these advancements, the cure rate ...

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nature.com

nature.com/articles/s41408-025-01270-4

Venetoclax schedule in AML: 7 vs 14 vs 21 vs 28 days

Topline results included similar CR/CRi (72% each) and overall survival (11.2 vs 10.3 months), however, early mortality at 8 weeks (6% vs 16%) ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40348597/

The Clinical Safety and Efficacy of Cytarabine ...

Results: CPX-351 exhibited an adverse event profile that was comparable to that of conventional chemotherapy. It resulted in complete remission rates of 18%-41% ...

7.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e18535

Real-world outcomes of cytarabine consolidation in older ...

Conclusions: Cytarabine consolidation in patients ≥60 years with AML is safe and feasible. Neurotoxicity was rare, especially at reduced dose.

8.

sciencedirect.com

sciencedirect.com/science/article/pii/S253113792300161X

Toxicity and outcome of adults with acute myeloid leukemia ...

In conclusion, our data suggest that high-dose of cytarabine (18 g/m2) is a safe option after induction of AML. Conflicts of interest. None. Recommended ...

9.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12063066/

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It resulted in complete remission rates of 18%–41% in relapsed/refractory AML patients. For newly diagnosed individuals, CPX‐351 led to complete ...

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Venetoclax plus daunorubicin and cytarabine for newly ...

In a phase 1b study, we assessed the safety and efficacy of Ven with daunorubicin and cytarabine in patients with newly diagnosed AML. A total ...