Venetoclax + Cytarabine for Acute Myeloid Leukemia

Recruiting at 108 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AbbVie

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

211 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests if venetoclax with low-dose cytarabine helps untreated AML patients who can't have intensive chemotherapy. Venetoclax works by blocking a protein that keeps cancer cells alive, making it easier to kill them. Venetoclax has been effective in treating leukemia when used with other treatments.

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.

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

Research shows that the combination of Venetoclax and low-dose Cytarabine improved response rates and overall survival in patients with newly diagnosed acute myeloid leukemia who were not eligible for intensive chemotherapy, compared to a placebo with low-dose Cytarabine. ^{1 2 3 4 5}

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

The combination of Venetoclax and low-dose Cytarabine has been studied in patients with acute myeloid leukemia, showing a favorable safety profile with a low rate of early treatment-related deaths, even in frail patients. However, there is a risk of tumor lysis syndrome (a condition where cancer cells break down rapidly) that requires careful management during treatment initiation. ^{1 2 4 5 6}

What makes the drug combination of Venetoclax and Cytarabine unique for treating acute myeloid leukemia?

The combination of Venetoclax and low-dose Cytarabine is unique because it offers improved response rates and overall survival for patients with acute myeloid leukemia who cannot undergo intensive chemotherapy, compared to using Cytarabine alone. This combination is particularly beneficial for those who are ineligible for more aggressive treatments. ^{1 2 5 6 7}

Research Team

AbbVie Inc.

Principal Investigator

AbbVie

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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 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]

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 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]

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 patients with newly diagnosed acute myeloid leukemia ineligible for intensive chemotherapy: an expanded access study in Japan. [2023]

2. England pubmed.ncbi.nlm.nih.gov

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

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

Clinical and molecular predictors of response and survival following venetoclax therapy in relapsed/refractory AML. [2021]

4. England pubmed.ncbi.nlm.nih.gov

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

5. United States 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). [2022]

6. England pubmed.ncbi.nlm.nih.gov

Real-world analysis of tumor lysis syndrome in patients started on venetoclax combination for acute myeloid leukemia. [2023]

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

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