Venetoclax + Decitabine for Acute Myeloid Leukemia

Overseen By Cancer Clinical Trials Office

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Chicago

Must not be taking: Venetoclax, Decitabine, Azacitidine

Disqualifiers: HIV, CNS involvement, Active infection, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety of a new drug combination, Venetoclax and Decitabine, for individuals with acute myeloid leukemia (AML), a type of blood cancer. It aims to assess patient tolerance to these drugs when used together. The trial seeks participants with high-risk AML, including those whose disease has returned, not responded to treatment, or involves specific genetic changes. Participants should not have received prior treatment with Venetoclax or Decitabine and must be free of certain other health issues. 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 taking your current medications, but you cannot take certain treatments like chemotherapy, radiation, or specific drugs that affect liver enzymes within a week before starting the study. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that the combination of Venetoclax and Decitabine is generally well-tolerated by patients with acute myeloid leukemia (AML). In studies with older AML patients, this treatment proved both effective and well-received. Researchers reported no unexpected safety issues. Common side effects included low blood cell counts, often seen with treatments for blood cancers. These findings suggest the treatment is relatively safe for humans, although side effects can still occur. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for acute myeloid leukemia?

Researchers are excited about Venetoclax and Decitabine as a combination treatment for Acute Myeloid Leukemia (AML) because they offer a unique approach compared to standard chemotherapy options. Most treatments for AML focus on killing rapidly dividing cells, but Venetoclax works differently by targeting a protein called BCL-2, which helps cancer cells survive. This makes cancer cells more vulnerable to Decitabine, which can then more effectively disrupt their DNA. By combining these mechanisms, this treatment has the potential to enhance effectiveness and improve outcomes for patients who may not respond well to traditional therapies.

What evidence suggests that Venetoclax and Decitabine might be an effective treatment for acute myeloid leukemia?

Research has shown that venetoclax, a medicine that helps kill cancer cells, holds promise for treating acute myeloid leukemia (AML). In this trial, participants will receive a combination of venetoclax and decitabine. Studies have found that this combination works well and is safe, especially for older patients with AML. It has demonstrated good results in terms of safety and effectiveness, with many patients responding positively. Additionally, it has been effective for patients who have not tried other treatments before. Overall, this combination targets cancer cells effectively and offers hope for people with AML. ^{1 3 5 6 7}

Who Is on the Research Team?

Olatoyosi M. Odenike

Principal Investigator

University of Chicago

Are You a Good Fit for This Trial?

Adults with acute myeloid leukemia (AML) can join this trial. Phase 1 is for those with high-risk AML, including relapsed or refractory disease and specific genetic changes. They must have good organ function and not be on certain treatments recently. Phase 2 is specifically for untreated AML patients with TP53 mutations. Pregnant women, HIV-positive individuals, and those with other significant health issues cannot participate.

Inclusion Criteria

My AML is considered high risk.

My condition has returned or didn't respond to treatment.

My leukemia is TP53 mutant.

Exclusion Criteria

I have been diagnosed with acute promyelocytic leukemia.

My leukemia has spread to my brain or spinal cord.

I am not taking any strong medications that affect liver enzymes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Cycle 1

Cycle 1 of Treatment will be Decitabine days 1-10 plus Venetoclax ramp up on days 1-3 followed by Venetoclax target dose on days 4-21

3 weeks

Treatment Cycle 2

Cycle 2 of Treatment will be Decitabine days 1-10 plus Venetoclax target dose days 1-21

3 weeks

Maintenance

During maintenance Decitabine on days 1-5 plus Venetoclax days 1-21

3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Decitabine
• Venetoclax

Trial Overview The study tests the safety of Venetoclax combined with Decitabine in treating AML. Participants will receive both drugs to see how well they tolerate them and what effects they have on their leukemia.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 2 Interventions

Cycle 1 of Treatment will be Decitabine days 1-10 plus Venetoclax ramp up on days 1-3 followed by Venetoclax target dose on days 4-21 Cycle 2 of Treatment will be Decitabine days 1-10 plus Venetcolax target dose days 1-21 During maintenance Decitabine on days 1-5 plus Venetoclax days 1-21

Decitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Dacogen for:

• Acute myeloid leukemia
• Myelodysplastic syndromes

Approved in United States as Dacogen for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Approved in Canada as Dacogen for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Approved in Japan as Dacogen for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

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 phase 1/2 study involving six Japanese patients aged 60 and older with acute myeloid leukaemia, the combination of venetoclax and azacitidine demonstrated a high response rate, with 83% of patients achieving a response, including three complete remissions.

The treatment was generally well tolerated, with a median overall survival of 15.7 months, although some patients experienced serious adverse events, including grade 3 fungal pneumonia, which required treatment adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax in combination with azacitidine in Japanese patients with acute myeloid leukaemia: phase 1 trial findings. Taniguchi, S., Yamauchi, T., Choi, I., et al.[2021]

In a phase 2 trial involving 168 patients with acute myeloid leukaemia (AML), the combination of venetoclax and a 10-day regimen of decitabine resulted in a high overall response rate of 74%, with particularly impressive results in newly diagnosed AML patients (89%).

The treatment demonstrated a manageable safety profile, with common adverse events including neutropenia and infections, and a 30-day mortality rate of only 3.6%, indicating that this combination therapy is both effective and relatively safe for older patients or those unfit for intensive chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

10-day decitabine with venetoclax for newly diagnosed intensive chemotherapy ineligible, and relapsed or refractory acute myeloid leukaemia: a single-centre, phase 2 trial. DiNardo, CD., Maiti, A., Rausch, CR., et al.[2021]

The VA regimen, combining venetoclax and azacitidine, demonstrated a high complete remission (cCR) rate of 78.8% after the first treatment cycle and 81.8% after prolonged treatment in 66 patients with newly diagnosed acute myeloid leukemia (AML) who were not suitable for conventional chemotherapy.

The treatment was generally safe, with manageable adverse effects, primarily neutropenia, thrombocytopenia, and anemia, and showed better outcomes in patients with specific gene mutations (IDH1/2 or NPM1) and those experiencing rebound thrombocytosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy of venetoclax combined azacitidine in newly diagnosed acute myeloid leukemia unfit for standard chemotherapy: a single center experience]. Sun, L., Ye, SJ., Zhou, N., et al.[2023]

In a study comparing older adults with newly diagnosed acute myeloid leukemia (AML), those treated with the combination of decitabine (DEC) and venetoclax (VEN) had a significantly longer median overall survival of 13.4 months compared to 8.3 months for those receiving DEC alone.

The combination therapy also resulted in a higher response rate of 70.3% versus 24.3% for DEC monotherapy, indicating that DEC+VEN is more effective in treating AML without increasing short-term mortality rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax with decitabine versus decitabine monotherapy in elderly acute myeloid leukemia: a propensity score-matched analysis. Kwag, D., Cho, BS., Bang, SY., et al.[2022]

In a study of 22 heavily pre-treated patients with relapsed or refractory acute myeloid leukaemia (RR-AML), the combination of venetoclax and decitabine resulted in a 45.5% overall response rate, with 40.9% achieving complete remission, demonstrating its efficacy in a real-world setting.

While the treatment was effective, it was associated with significant side effects, including grade IV neutropenia and thrombocytopenia in all patients, but no deaths were attributed to the treatment side effects, indicating that the adverse effects were manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Venetoclax Combined with Decitabine-Based Treatment for Heavily Pre-Treated Relapsed or Refractory AML Patients in a Real-World Setting. Tong, J., Zhao, N., Hu, X., 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]

In a study of 81 patients with acute myeloid leukemia (AML) receiving venetoclax with decitabine or azacitidine, 72.8% experienced infections, with the most common pathogens being Candida albicans and Klebsiella pneumonia.

The study found that the incidence of infectious complications was lower with this treatment compared to conventional chemotherapy, and high leukemia burden and fever were identified as significant risk factors for developing infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A real-world study of infectious complications of venetoclax combined with decitabine or azacitidine in adult acute myeloid leukemia. Zhu, LX., Chen, RR., Wang, LL., et al.[2022]

Venetoclax, a BCL-2 inhibitor, shows promise in combination therapies for newly diagnosed or relapsed acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), achieving high remission rates and deep molecular responses.

Despite these encouraging results, there are concerns about side effects such as incomplete blood count recovery and increased infection rates, particularly when used with chemotherapy, and more research is needed to understand the long-term effectiveness and durability of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax combination therapy in acute myeloid leukemia and myelodysplastic syndromes. Shimony, S., Stone, RM., Stahl, M.[2023]

In a study involving 145 older patients (median age 74) with acute myeloid leukemia (AML) who were ineligible for intensive chemotherapy, the combination of venetoclax with decitabine or azacitidine resulted in a high complete remission (CR) rate of 67%, demonstrating its efficacy in this challenging population.

The treatment was well tolerated, with no cases of tumor lysis syndrome reported, and the median overall survival was 17.5 months, indicating that venetoclax combined with hypomethylating agents is a promising option for elderly patients with AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. DiNardo, CD., Pratz, K., Pullarkat, V., et al.[2021]

A once-weekly low-dose decitabine (LDDec) combined with venetoclax (VEN) showed high efficacy in treating elderly patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), achieving an overall response rate of 88% for AML and 64% for MDS in a retrospective study of 39 patients.

Patients receiving the LDDec/VEN regimen experienced longer treatment durations and a trend towards higher transfusion independence compared to those on standard dosing, suggesting that this approach may reduce severe myelosuppression while maintaining effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Metabolically Optimized, Noncytotoxic Low-Dose Weekly Decitabine/Venetoclax in MDS and AML. Levitz, D., Saunthararajah, Y., Fedorov, K., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02203773

NCT02203773 | Study of ABT-199 (GDC-0199) in ... This is a Phase 1b, open-label, non-randomized, multicenter study to evaluate the safety and pharmacokinetics of orally administered venetoclax (ABT-199) ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6499443/

Evaluating venetoclax and its potential in treatment-naïve ... Venetoclax (ABT-199), a BH3-mimetic and selective BCL-2 inhibitor, was recently approved by the US Food and Drug Administration (FDA) for the treatment of acute ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03941964

NCT03941964 | A Study of the Effectiveness of Venetoclax ... A study evaluating the effectiveness and safety of venetoclax, in combination with azacitidine or decitabine, in an outpatient setting for treatment-naïve ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0006497118473065

A Phase 1b Study of Venetoclax (ABT-199/GDC-0199) in ... Venetoclax (VEN) is a selective, potent, orally bioavailable BCL-2 inhibitor that has demonstrated single-agent activity in AML cell lines, primary pt samples, ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6318429/

Venetoclax combined with decitabine or azacitidine in ... The novel combination of venetoclax with decitabine or azacitidine was effective and well tolerated in elderly patients with AML.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12032727/

Meta-analysis on the effectiveness and safety of venetoclax ... Real-world outcomes of frontline venetoclax-based therapy in older adults with acute myeloid leukemia: an analysis utilizing EHR data. Leuk ...

7. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30010-X/abstract

Safety and preliminary efficacy of venetoclax with ... Elderly patients (aged ≥65 years) with acute myeloid leukaemia have poor outcomes and no effective standard-of-care therapy exists.