Venetoclax + Chemotherapy for Acute Myeloid Leukemia

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Richard Stone, MD

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Dana-Farber Cancer Institute

Must not be taking: CYP3A inducers, CYP3A inhibitors

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

No Placebo Group

Breakthrough Therapy

Trial Summary

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

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}

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.

Trial 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 (Antimetabolite)
• Daunorubicin (Anthracycline)
• Venetoclax (BCL-2 Inhibitor)

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University of Chicago Chicago, IL

Dana Farber Cancer Institute Boston, MA

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute Lead Sponsor

Genentech, Inc. Industry Sponsor

AbbVie Industry Sponsor

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] In a multinational phase 3 trial (VIALE-C), venetoclax plus low-dose cytarabine prolonged overall survival vs placebo plus low-dose cytarabine in patients with newly diagnosed acute myeloid leukaemia ineligible for intensive chemotherapy, although it was not statistically significant. Herein, we assess the benefit of venetoclax plus low-dose cytarabine in the Japanese subgroup of VIALE-C patients (n = 27).

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] Venetoclax (Ven) combined with intensive chemotherapy was proven effective in the management of acute myeloid leukemia (AML). However, the severe and prolonged myelosuppression remains a concern to worry about. To explore more appropriate combination regimens, we designed Ven combining daunorubicin and cytarabine (DA 2 + 6) regimen as induction therapy, aimed to evaluate the effectiveness and safety in adults de novo AML.

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] In a Phase 3 international clinical trial (VIALE-C), venetoclax plus low-dose cytarabine improved the response rate and overall survival versus placebo plus low-dose cytarabine in patients with newly diagnosed acute myeloid leukemia who were ineligible for intensive chemotherapy. After the enrollment period of VIALE-C ended, we conducted an expanded access study to provide preapproval access to venetoclax in combination with low-dose cytarabine in Japan.

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] Adults with acute myeloid leukaemia have unsatisfactory clinical outcomes and rates of complete remission. Venetoclax combined with azacytidine or low-dose cytarabine has shown efficacy in adults aged 75 years or older (or 18-74 years with comorbidities precluding intensive chemotherapy) with acute myeloid leukaemia. We aimed to investigate the activity and safety of venetoclax plus 3+7 daunorubicin and cytarabine chemotherapy in adults with acute myeloid leukaemia.

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

Venetoclax-containing regimens in acute myeloid leukemia. [2021] Venetoclax in combination with hypomethylating agents (HMAs) or low-dose cytarabine (LDAC) has demonstrated exceptional activity in elderly and unfit patients with newly diagnosed acute myeloid leukemia (AML). Notably, the safety profile of venetoclax-based induction regimens was favorable, with a low rate of early treatment-related mortality, even in frail study participants. Thus, the introduction of venetoclax has transformed the landscape of AML therapy in elderly patients. Given these promising results, venetoclax in combination with other agents is now being studied as a frontline therapy in younger patients with AML, as well as in relapsed/refractory AML patients. Here, we review clinical data for venetoclax-based therapy in AML, both from prospective as well as retrospective studies, and highlight ongoing novel studies of venetoclax-containing regimens and discuss future research directions.

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

Venetoclax in combination with nucleoside analogs in acute myelogenous leukemia. [2023] Venetoclax in combination with nucleoside analogs such as hypomethylating agents (HMA) and low-dose cytarabine (LDAC) has led to unprecedented response and survival outcomes in patients with acute myeloid leukemia (AML). This has spurred the development of regimens combining venetoclax with other nucleoside analogs with distinct mechanisms of action. Here, we review older and newer nucleoside analogs, the rationale for their combination with venetoclax, and clinical evidence for the combination when available.