Venetoclax Combination Therapy for Acute Myeloid Leukemia

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: OHSU Knight Cancer Institute

Must not be taking: CYP3A4 inducers/inhibitors

Disqualifiers: CNS involvement, Active malignancy, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of medications to evaluate their effectiveness in treating acute myeloid leukemia (AML), a specific type of blood cancer. The treatment includes venetoclax, which helps stop cancer cell growth, along with chemotherapy drugs such as azacitidine, cladribine, and cytarabine, which aim to kill or prevent the spread of these cells. The trial seeks individuals newly diagnosed with monocytic AML or with certain gene mutations in their AML who cannot or do not wish to undergo standard intensive chemotherapy. Participants should be willing to provide bone marrow samples and adhere to specific care routines during the trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot use drugs that strongly interact with the study drugs, particularly strong or moderate CYP3A4 inducers or inhibitors, within 2 days or 3 half-lives before starting the trial. It's best to discuss your current medications with the trial team.

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

Research has shown that combining venetoclax with cladribine, cytarabine, and azacitidine has been studied for treating acute myeloid leukemia (AML). This combination has proven effective for some patients, but safety remains a major concern.

Studies indicate that venetoclax is generally well-tolerated in older AML patients, especially when used with azacitidine. However, common side effects, like low blood cell counts, require careful management by healthcare providers.

Venetoclax has received full approval for use in some AML patients, indicating that its safety profile is well understood. When combined with azacitidine, it is often prescribed for patients who might not tolerate more aggressive treatments.

Cladribine and cytarabine, chemotherapy drugs with a long history of use, work by killing cancer cells or stopping their growth. Like all chemotherapy drugs, they can cause side effects such as nausea or fatigue, but doctors are adept at managing these.

Overall, this drug combination has shown promise in treating AML. While side effects exist, they are usually manageable with medical guidance. Anyone considering joining a trial should discuss potential risks and benefits with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for acute myeloid leukemia (AML) because it combines venetoclax, cladribine, and cytarabine, potentially enhancing its effectiveness. Unlike standard treatments like daunorubicin and cytarabine alone, this combination includes venetoclax, which targets BCL-2, a protein that helps cancer cells survive. This targeted approach may lead to better outcomes by specifically attacking cancer cell survival mechanisms. Additionally, combining these drugs could potentially reduce the time needed to see positive patient responses.

What evidence suggests that this trial's treatments could be effective for acute myeloid leukemia?

This trial will evaluate the combination of venetoclax with cladribine, cytarabine, and azacitidine for treating acute myeloid leukemia (AML). Studies have shown that venetoclax, which blocks a protein called BCL-2 that helps cancer cells survive, can be effective in this combination. By blocking this protein, the growth of cancer cells may be stopped. Research indicates that this combination can lead to quick and lasting improvements, especially in patients who cannot undergo intensive treatments. Additionally, using these drugs together might kill more cancer cells than using them separately. Overall, early findings suggest this combination could be a promising treatment for AML. ^{1 2 5 6 7}

Who Is on the Research Team?

Curtis A Lachowiez

Principal Investigator

OHSU Knight Cancer Institute

Are You a Good Fit for This Trial?

This trial is for patients with newly diagnosed monocytic AML or active signaling mutated AML. Specific eligibility criteria are not provided, but typically participants must meet certain health standards and may be required to have a particular type of cancer.

Inclusion Criteria

I understand this study is experimental and I can give my consent.

I am willing to receive care for side effects related to blood issues, infections, and immediate aftereffects.

Negative urine pregnancy test at screening and within 24 hours of cycle 1 day 1 for persons of childbearing potential

Exclusion Criteria

My AML has spread to my brain or spinal cord and is causing symptoms.

I have not had another cancer in the last 5 years.

Investigational therapy within 28 days of C1D1

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Patients receive cladribine, cytarabine, and venetoclax to induce remission

4 weeks

Multiple visits for drug administration

Re-Induction

Patients with > 5% blasts after cycle 1 receive additional treatment to achieve remission

4 weeks

Multiple visits for drug administration

Remission After Induction

Patients achieving remission receive further treatment to consolidate response

4 weeks

Multiple visits for drug administration

Continuing Therapy

Patients receive alternating cycles of venetoclax and azacitidine or cladribine and cytarabine

Up to 18 cycles (each cycle is 4 weeks)

Regular visits for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Periodic visits for monitoring

What Are the Treatments Tested in This Trial?

Interventions

• Azacitidine
• Cladribine
• Cytarabine
• Venetoclax

Trial Overview The trial tests venetoclax combined with cladribine and cytarabine, alternating with azacitidine plus venetoclax. It's a phase II study to see if this regimen can effectively kill more cancer cells in the specified patient group.

How Is the Trial Designed?

Group I: Treatment (venetoclax, cladribine, cytarabine, azacitidine) Experimental Treatment 11 Interventions

See Detailed Description

Cladribine is already approved in United States, European Union for the following indications:

Approved in United States as Leustatin for:

• Hairy cell leukemia
• Chronic lymphocytic leukemia (CLL)
• Non-Hodgkin's lymphoma
• Multiple sclerosis

Approved in European Union as Litak for:

• Hairy cell leukemia
• Chronic lymphocytic leukemia (CLL)
• Non-Hodgkin's lymphoma

Who Is Running the Clinical Trial?

OHSU Knight Cancer Institute

Lead Sponsor

Trials

239

Recruited

2,089,000+

Oregon Health and Science University

Collaborator

Trials

1,024

Recruited

7,420,000+

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

In a study of 6 children with refractory or relapsed acute myeloid leukemia (AML), the combination of venetoclax, azacitidine, and cladribine (VAC regimen) resulted in significant treatment responses, with 4 achieving complete remission and 1 showing partial remission.

Despite severe side effects like grade IV neutropenia and thrombocytopenia, there were no treatment-related deaths or infections, indicating that the VAC regimen is both effective and safe for this vulnerable patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Safety and the Short-Term Efficacy of Venetoclax Combined with Azacitidine Followed by Cladribine in Children with Refractory/Relapsed Acute Myeloid Leukemia]. DU, WW., Liu, SX., Wang, Y., 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 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]

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 comparison of two combination therapies for acute myeloid leukemia—glasdegib+low-dose cytarabine (LDAC) and venetoclax+LDAC—no statistically significant differences in overall survival or complete remission rates were found, suggesting similar efficacy.

When choosing between these treatments, factors like safety profiles, ease of administration, and patient preferences will be important since both therapies appear equally effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of glasdegib versus venetoclax combined with low-dose cytarabine in acute myeloid leukemia. Tremblay, G., Daniele, P., Bell, T., et al.[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 study comparing treatment regimens for relapsed/refractory acute myeloid leukemia (R/R AML), the venetoclax (VEN) combination therapy showed a comparable overall response rate (59.3%) to intensive chemotherapy (IC) (44.0%), suggesting it is an effective alternative for patients who have failed previous treatments.

Patients receiving the VEN combination had a significantly higher percentage of successful stem cell transplants at blast clearance (86.5% vs. 62.3% for IC), indicating better disease control and potentially lower treatment-related mortality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective comparison of salvage intensive chemotherapy versus venetoclax-combined regimen in patients with relapsed/refractory acute myeloid leukemia (AML). Park, S., Kwag, D., Kim, TY., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03586609

NCT03586609 | Venetoclax, Cladribine, Low Dose ... This phase II trial studies how well venetoclax, cladribine, low dose cytarabine, and azacitidine work in treating patients with acute myeloid leukemia that ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11707511/

Venetoclax-Based Combination Regimens in Acute Myeloid ... Overall, the results from this study suggest that venetoclax added to FLAG/idarubicin serves as an effective addition to intensive chemotherapy, with a ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06504459

Study Details | NCT06504459 | Venetoclax in Combination ... Giving venetoclax with cladribine and cytarabine alternating with azacitidine and venetoclax may kill more cancer cells in patients with newly diagnosed ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.18.01600

Venetoclax Combined With Low-Dose Cytarabine for ... Venetoclax plus LDAC has a manageable safety profile, producing rapid and durable remissions in older adults with AML ineligible for intensive chemotherapy.

5. haematologica.org haematologica.org/article/view/11526

Cladribine plus cytarabine plus venetoclax in acute ... Efficacy and safety of cladribine, low-dose cytarabine and venetoclax in relapsed/refractory acute myeloid leukemia: results of a pilot study.

6. link.springer.com link.springer.com/article/10.1007/s00277-025-06643-0

Efficacy and safety of venetoclax plus azacitidine based ... This meta-analysis aimed to evaluate the efficacy and safety of venetoclax plus azacitidine (VEN + AZA) regimens in patients with relapsed ...

7. ashpublications.org ashpublications.org/blood/article/145/12/1237/517960/How-I-treat-patients-with-AML-using-azacitidine

How I treat patients with AML using azacitidine and venetoclax Venetoclax (VEN) received full approval in October 2020 for use in older patients who are unfit with acute myeloid leukemia (AML) combined with either ...