Discontinuing Decitabine/Azacitidine + Venetoclax for AML

Overseen By Gina Bellenger

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must be taking: Azacitidine, Decitabine, Venetoclax

Must not be taking: Cytotoxic agents, Experimental agents

Disqualifiers: TP53 mutation, CNS involvement, 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

37 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether individuals with Acute Myeloid Leukemia (AML) who respond successfully to the chemotherapy combination of azacitidine or decitabine and venetoclax can safely discontinue treatment after a year without experiencing a return of leukemia. The goal is to determine if stopping these drugs is possible without increasing the risk of relapse. Suitable participants for this trial include those with AML who are in complete remission and have been on azacitidine or decitabine and venetoclax for less than a year. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants the opportunity to contribute to significant findings.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does require that you are currently on azacitidine or decitabine with venetoclax for AML treatment. If you are taking other experimental or cytotoxic drugs for AML, you must stop them at least 28 days before starting the study.

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

Research has shown that the combination of azacitidine and venetoclax is generally safe for patients with acute myeloid leukemia (AML). Doctors are familiar with the side effects of this treatment and know what to expect. Importantly, trials revealed no new warnings or precautions, making it a manageable option for many patients.

Similarly, the combination of decitabine and venetoclax is also considered safe. Studies indicate that this combination is effective and has fewer side effects compared to some traditional chemotherapy treatments. Both treatment options, using venetoclax with either azacitidine or decitabine, have been found safe in previous studies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it explores a new approach to managing acute myeloid leukemia (AML) by strategically discontinuing treatment while maintaining close monitoring. Unlike the standard continuous treatment with azacitidine, decitabine, and venetoclax, this method allows patients to pause therapy if they achieve a negative measurable residual disease (MRD) status, potentially reducing side effects and improving quality of life. This protocol offers the possibility of reinitiating treatment quickly if there are signs of relapse, providing a flexible and responsive approach to managing the disease.

What evidence suggests that discontinuing azacitidine/decitabine and venetoclax might be effective for AML?

Research shows that combining azacitidine or decitabine with venetoclax holds promise for treating acute myeloid leukemia (AML). In this trial, participants will receive either azacitidine or decitabine with venetoclax during the consolidation phase. Studies have found that patients taking azacitidine with venetoclax achieve higher remission rates than those taking azacitidine alone. Similarly, combining decitabine with venetoclax proves effective and safer than traditional chemotherapy. Both combinations have demonstrated positive results, especially for older patients, indicating their potential to manage AML well. Overall, strong evidence supports these treatments for AML. ^{2 4 6 7 8}

Who Is on the Research Team?

Onyee Chan, MD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with Acute Myeloid Leukemia (AML) who are responding well to treatment with azacitidine or decitabine plus venetoclax. They must have completed at least a year of this therapy without their AML returning.

Inclusion Criteria

I have been diagnosed with a specific type of leukemia (AML, non-M3).

I can do most of my daily activities by myself.

Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

Patient is pregnant

My cancer was diagnosed with a TP53 mutation.

I haven't used certain strong cancer drugs or experimental treatments for AML in the last 28 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Consolidation

Participants receive HMA (azacitidine or decitabine) and VEN (venetoclax) as part of standard of care treatment

12 months

Discontinuation

Participants undergo monthly clinic visits with laboratory assessment and bone marrow biopsies every 3 months to monitor disease status

Up to 36 months

Monthly clinic visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Azacitidine
• Decitabine
• Venetoclax

Trial Overview The study investigates whether patients can safely stop taking the chemotherapy drugs azacitidine or decitabine in combination with venetoclax after one year of successful treatment, without increasing the risk of AML recurrence.

How Is the Trial Designed?

Group I: Consolidation and Discontinuation Experimental Treatment 3 Interventions

Consolidation: Patient will receive HMA (azacitidine or decitabine)/VEN (venetoclax) as part of standard of care treatment. At the conclusion of consolidation, if the results of the bone marrow biopsy are a negative Measurable Residual Disease (MRD), patient will continue to Discontinuation. Discontinuation: Monthly clinic visits with laboratory assessment and bone marrow biopsies (BMBs) with MRD testing every 3 months to closely monitor disease status. At any point of the study if molecular relapse (including MRD emergence), or morphologic relapse, therapy will be reinitiated. If only molecular relapse, HMA (azacitidine or decitabine)/VEN (venetoclax) will be reinitiated with the same monitoring schedule as before. If morphologic relapse, HMA (azacitidine or decitabine)/VEN (venetoclax) will be reinitiated for 2 cycles. If no response (NR), patient will be taken off Study.

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

Approved in European Union as Vidaza for:

• Acute myeloid leukemia
• Chronic myelomonocytic leukemia
• Myelodysplastic syndromes

Approved in United States as Vidaza for:

• Myelodysplastic syndromes
• Chronic myelomonocytic leukemia

Approved in Canada as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Approved in Japan as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

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 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]

Venetoclax, when combined with azacitidine, has shown effectiveness in treating a 73-year-old patient with acute myeloid leukemia (AML) who was undergoing dialysis and ineligible for standard therapies.

The combination of venetoclax and azacitidine appears to be a safe and feasible treatment option for AML patients with comorbidities, such as those requiring dialysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Administration of combined venetoclax and azacitidine in a patient with acute myeloid leukemia and multiple comorbidities undergoing dialysis: A case report. Akagi, Y., Yamashita, Y., Kosako, H., et al.[2023]

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 study of 45 elderly patients with relapsed acute myeloid leukemia, the combination of venetoclax (VEN) and azacitidine (AZA) resulted in a significantly higher overall remission rate (ORR) of 77.8% compared to 37.0% for the CAG regimen with decitabine (DAC), indicating better efficacy for the VEN and AZA combination.

The VEN and AZA treatment was associated with lower incidences of severe adverse events, such as grade Ⅲ-Ⅳ cytopenia and infections, suggesting it is a safer option for elderly patients compared to the CAG with DAC regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of venetoclax combined with azacitidine versus CAG regimen combined with decitabine in elderly patients with relapsed acute myeloid leukemia]. Wang, P., Zhang, LW., Lu, CQ., et al.[2022]

In patients with newly diagnosed unfit acute myeloid leukemia (AML), the combination of azacitidine and venetoclax is a standard first-line treatment.

However, patients with TP53-mutated AML and poor-risk cytogenetics do not benefit from adding venetoclax to azacitidine, suggesting that alternative treatment regimens should be considered for these individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TP53 or Not TP53: That Is the Question. Green, SD., Zeidner, JF.[2023]

In a phase II study involving 60 older or unfit patients with newly diagnosed acute myeloid leukemia (AML), the combination of venetoclax with cladribine and low-dose cytarabine alternating with venetoclax and 5-azacitidine resulted in a high composite complete response rate of 93%.

The treatment showed promising overall survival and disease-free survival rates, with only one death occurring within 4 weeks, indicating that this regimen is effective and has a favorable safety profile for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Study of Venetoclax Added to Cladribine Plus Low-Dose Cytarabine Alternating With 5-Azacitidine in Older Patients With Newly Diagnosed Acute Myeloid Leukemia. Kadia, TM., Reville, PK., Wang, X., et al.[2023]

In the HiDDAV study involving 42 newly diagnosed AML patients, higher doses of venetoclax (600 mg daily) were found to be tolerable but did not show significant clinical improvement compared to the standard 400 mg dose.

The study revealed that using minimal residual disease (MRD) status to guide the discontinuation of azacitidine did not lead to better outcomes in terms of duration of response or overall survival, suggesting that alternative strategies are needed to optimize treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Higher-dose venetoclax with measurable residual disease-guided azacitidine discontinuation in newly diagnosed acute myeloid leukemia. Gutman, JA., Winters, A., Kent, A., et al.[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]

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]

Citations

1. nature.com nature.com/articles/s41375-025-02730-3

Outcomes of patients treated with venetoclax plus ... The 5-year relative survival of patients with AML is ~32%, and survival rates are dependent on age at diagnosis. Patients <50 years of age have ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12422247/

Efficacy of Venetoclax Combined with Azacitidine in Elderly ... Venetoclax combined with azacitidine has shown promising activity in newly diagnosed or relapsed/refractory AML, but real-world data on older ...

3. hematologyadvisor.com hematologyadvisor.com/news/combination-azacitidine-venetoclax-acute-myeloid-leukemia-aml-treatment-risk/

Combination Azacitidine, Venetoclax Effective in AML ... Analysis showed that the overall response rates in the azacitidine plus venetoclax, chemotherapy, and azacitidine monotherapy groups were 38.5%, ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa2012971

Azacitidine and Venetoclax in Previously Untreated Acute ... The incidence of remission was higher among patients who received azacitidine plus venetoclax than among those who received azacitidine alone.

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e18509

Comparative safety and effectiveness of azacitidine plus ... In AML patients aged 60–75 years, HMA&Ven demonstrated comparable all-cause mortality to IC and significantly lower risk of several adverse events.

6. venclextahcp.com venclextahcp.com/aml/side-effects/ven-aza-safety-profile.html

VEN+AZA: Summary of safety data from the VIALE-A trial A tolerable, manageable, and predictable safety profile1. No additional warnings or precautions were observed in the AML trials for VENCLEXTA (venetoclax ...

7. ashpublications.org ashpublications.org/blood/article/145/11/1126/534406/Efficacy-and-safety-of-venetoclax-plus-azacitidine

Efficacy and safety of venetoclax plus azacitidine for patients ... Key PointsVenetoclax (14 days) + azacitidine regimen was well tolerated in patients with treatment-naive HR MDS, with no unexpected safety ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04161885

NCT04161885 | A Study Evaluating Safety and Efficacy of ... The main objective of this study is to evaluate the efficacy of venetoclax in combination with azacitidine to improve Overall Survival (OS) in Acute Myeloid ...