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

Trial Summary

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.

What data supports the effectiveness of the drug combination Venetoclax and chemotherapy for treating acute myeloid leukemia?

Research shows that combining Venetoclax with low-dose cytarabine or daunorubicin and cytarabine improves response rates and overall survival in patients with acute myeloid leukemia, especially those who are older or cannot undergo intensive chemotherapy. These combinations have shown promising results in both international and Japanese studies, transforming treatment options for this condition. ^{1 2 3 4 5}

Is the combination of Venetoclax and chemotherapy safe for treating acute myeloid leukemia?

The combination of Venetoclax with chemotherapy for acute myeloid leukemia has shown a favorable safety profile, with a low rate of early treatment-related deaths, even in frail patients. However, severe and prolonged myelosuppression (a decrease in bone marrow activity leading to fewer blood cells) is a concern. ^{1 2 3 4 5}

How is the drug combination of Venetoclax, Cytarabine, and Daunorubicin unique for treating acute myeloid leukemia?

This drug combination is unique because it includes Venetoclax, which targets a specific protein (BCL-2) that helps cancer cells survive, and is combined with chemotherapy drugs Cytarabine and Daunorubicin to improve treatment effectiveness, especially for patients who cannot undergo intensive chemotherapy. ^{1 2 3 4 6}

What is the purpose of this trial?

This research study is studying the combination of venetoclax and chemotherapy as a possible treatment for acute myelogenous leukemia (AML). The drugs involved in this study are: * Venetoclax * Daunorubicin * Cytarabine

Research Team

Richard Stone, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

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

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

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

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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]

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 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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Venetoclax plus low-dose cytarabine in Japanese patients with untreated acute myeloid leukaemia ineligible for intensive chemotherapy. [2022]

2. England 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. [2023]

3. England 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. [2023]

4. England 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. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Venetoclax-containing regimens in acute myeloid leukemia. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Venetoclax in combination with nucleoside analogs in acute myelogenous leukemia. [2023]