Venetoclax + Chemotherapy for Acute Myeloid Leukemia

Recruiting at 1 trial location

Overseen By Richard Stone, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Dana-Farber Cancer Institute

Must not be taking: CYP3A inducers, CYP3A inhibitors

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

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

Compensation: Varies

Number of Visits: Unknown

64 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for people with acute myeloid leukemia (AML), a cancer of the blood and bone marrow. Researchers are examining how well the drugs venetoclax (a targeted therapy), daunorubicin, and cytarabine work together against this type of leukemia. The trial targets those newly diagnosed with AML who have not received other treatments, except for hydroxyurea. Participants should not have certain genetic forms of AML or health issues like heart problems that could affect eligibility. 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 combination therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you must avoid certain drugs like strong or moderate CYP3A inducers and inhibitors within 7 days before starting the study treatment. It's best to discuss your current medications with the study team to ensure they don't interfere with the trial.

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

Research has shown that combining the drug venetoclax with the chemotherapy drugs daunorubicin and cytarabine may help treat acute myeloid leukemia (AML). In earlier studies, most patients tolerated this combination well, though some experienced side effects, which are common with strong cancer treatments.

The most common side effect was a drop in blood cell counts, increasing the risk of infections. Other side effects included nausea and tiredness, typical for chemotherapy.

Overall, the combination of venetoclax with daunorubicin and cytarabine has proven safe enough for further study. Ongoing research aims to confirm the effectiveness and safety of this treatment for people with AML. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Venetoclax with chemotherapy for treating Acute Myeloid Leukemia (AML) because it introduces a novel mechanism of action. Most traditional AML treatments, like Cytarabine and Daunorubicin, focus on killing rapidly dividing cells. Venetoclax, however, specifically targets and inhibits the BCL-2 protein, which helps cancer cells survive. This dual approach not only aims to enhance the overall effectiveness against the leukemia but also holds the potential for faster, more comprehensive results compared to standard chemotherapy alone.

What evidence suggests that the combination of venetoclax and chemotherapy could be an effective treatment for acute myeloid leukemia?

In this trial, participants will receive a combination of venetoclax, daunorubicin, and cytarabine. Research has shown that this combination holds promise for treating acute myeloid leukemia (AML). Studies have found that it can safely lead to MRD-negative remissions, effectively reducing the number of cancer cells in the body. This treatment has successfully helped patients reach remission, where the signs and symptoms of cancer are reduced. Various studies have tested it and found it effective in managing AML. Overall, evidence suggests that this treatment could be a strong option for those with AML. ^{6 7 8 9 10}

Who Is on the Research Team?

Richard Stone, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults aged 18-60 with newly diagnosed acute myelogenous leukemia (AML), including those evolved from other conditions like MDS, but not previously treated except possibly with hydroxyurea. Participants must have adequate heart, liver, and kidney function and cannot be pregnant or have active infections like HIV or hepatitis B/C. They should not have had any chemotherapy within the last month.

Inclusion Criteria

I am a woman who can have children and have a recent negative pregnancy test.

aspartate aminotransferase (AST) ≤ 2.5 × ULN*

total bilirubin ≤ 1.5 × ULN*

Exclusion Criteria

My leukemia has specific genetic changes known as inversion 16 or t(8;21).

My leukemia is of a specific type (APL, inversion16, t(8;21), or FLT3 mutant).

I have skin cancer that is either basal cell or squamous cell type.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Participants receive venetoclax with induction chemotherapy to determine the maximum tolerated dose

2-3 weeks

Daily visits for drug administration

Consolidation

Participants receive venetoclax with consolidation chemotherapy to determine the maximum tolerated dose

2-3 weeks

Daily visits for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Cytarabine
• Daunorubicin
• Venetoclax

Trial Overview The study tests a combination of venetoclax with two chemotherapy drugs, daunorubicin and cytarabine, as a potential treatment for AML. The goal is to see how well these medications work together in patients who haven't received prior AML-specific treatment.

How Is the Trial Designed?

Group I: Venetoclax+Daunorubicin+Cytarabine Experimental Treatment 3 Interventions

* Venetoclax administered orally on days 1 to 11 daily * Daunorubicin administered intravenously on days 2-4 * Cytarabine administered on days 2-8 by continuous IV infusion

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?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

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

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 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]

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 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]

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]

Citations

1. ashpublications.org ashpublications.org/blood/article/145/17/1870/535523/Venetoclax-plus-daunorubicin-and-cytarabine-for

Venetoclax plus daunorubicin and cytarabine for newly ... Key PointsVen can be safely used in combination with 7+3 chemotherapy for remission induction in patients with newly diagnosed AML.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39919267/

Venetoclax plus daunorubicin and cytarabine for newly ... Ven (400 mg), when combined with 7+3 chemotherapy, was safe and effective in achieving MRD-negative remissions across all durations.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05342584

Study Details | NCT05342584 | Venetoclax Plus Intensive ... Venetoclax plus daunorubicin and cytarabine for newly diagnosed acute myeloid leukemia: results of a phase 1b study. Blood. 2025 Apr 24;145(17):1870-1875 ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05628623

Testing the Use of Combination Therapy in Patients With ... The study is comparing the use of Cytarabine to Cytarabine and Venetoclax, Daunorubicin/Cytarabine Liposome and Venetoclax, and Azacitidine and Venetoclax.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10176670/

Venetoclax combined with daunorubicin and cytarabine (2 + 6 ... Venetoclax (Ven) combined with intensive chemotherapy was proven effective in the management of acute myeloid leukemia (AML).

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

Venetoclax Combined With Low-Dose Cytarabine for ... Venetoclax Combined With Low-Dose Cytarabine for Previously Untreated Patients With Acute Myeloid Leukemia: Results From a Phase Ib/II Study. Andrew H Wei ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06697327

Daunorubicin + Cytarabine + Venetoclax in de Novo AML To evaluate the safety of the regimen, as defined by Grade 3-4 clinical adverse events (AEs), incidence of laboratory abnormalities, and treatment-related ...

8. ehoonline.biomedcentral.com ehoonline.biomedcentral.com/articles/10.1186/s40164-023-00409-y

Venetoclax combined with daunorubicin and cytarabine (2 + 6 ... Venetoclax (Ven) combined with intensive chemotherapy was proven effective in the management of acute myeloid leukemia (AML).

9. ashpublications.org ashpublications.org/bloodadvances/article/8/24/6248/518219/Lower-intensity-CPX-351-plus-venetoclax-induction

Lower-intensity CPX-351 plus venetoclax induction for adults ... This study highlights that lower-intensity therapy of CPX-351 plus venetoclax as induction therapy provides a well-tolerated treatment option in adults with AML

10. aacrjournals.org aacrjournals.org/bloodcancerdiscov/article/6/1/23/750802/Venetoclax-Based-Combination-Regimens-in-Acute

Venetoclax-Based Combination Regimens in Acute Myeloid ... This review highlights the evolution of venetoclax-based regimens in AML and provides a commentary on notable practical considerations when utilizing this ...