Discontinuing Decitabine/Azacitidine + Venetoclax for AML

Recruiting in Palo Alto (17 mi)

Overseen by Onyee Chan, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

The purpose of this research study is to see if people whose Acute myeloid leukemia (AML) is being successfully treated with azacitidine or decitabine in combination with venetoclax can discontinue this chemotherapy for some period of time after a year of treatment without increasing the likelihood that their AML will return.

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.

What data supports the effectiveness of the drug combination of azacitidine and venetoclax for treating acute myeloid leukemia (AML)?

Research shows that combining venetoclax with azacitidine improves remission rates and survival in older or unfit patients with AML compared to azacitidine alone. Additionally, a study found that this combination leads to rapid deep remission in patients not suitable for standard chemotherapy, with a complete remission rate of 81.8% after prolonged treatment. ^{1 2 3 4 5}

Is the combination of venetoclax and azacitidine safe for treating acute myeloid leukemia?

The combination of venetoclax and azacitidine is generally considered safe for treating acute myeloid leukemia, with common side effects including bone marrow suppression, infections, nausea, vomiting, anorexia, and fatigue. Studies show that this combination has a lower incidence of severe blood-related side effects and infections compared to other regimens. ^{1 2 3 5 6}

How is the drug combination of Decitabine/Azacitidine and Venetoclax unique for treating AML?

This drug combination is unique because it offers a treatment option for older patients or those with other health issues who cannot undergo intensive chemotherapy, and it has shown promising results in improving remission rates and survival in these patients. ^{2 3 7 8 9}

Research Team

Onyee Chan, MD

Principal Investigator

Moffitt Cancer Center

Eligibility Criteria

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.

Must agree to adhere to the study visit schedule and other protocol requirements

Exclusion Criteria

My cancer was diagnosed with a TP53 mutation.

Patient is pregnant

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

Trial Timeline

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

Treatment Details

Interventions

• Azacitidine (Anti-metabolites)
• Decitabine (Anti-metabolites)
• Venetoclax (BCL-2 Inhibitor)

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.

Participant Groups

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 Canada, Japan for the following indications:

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+

Patrick Hwu

H. Lee Moffitt Cancer Center and Research Institute

Chief Executive Officer since 2020

MD from The Medical College of Pennsylvania

Wade J. Sexton

H. Lee Moffitt Cancer Center and Research Institute

Chief Medical Officer

MD

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

Findings from Research

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 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 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]

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]

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 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]

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]

References

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

TP53 or Not TP53: That Is the Question. [2023]

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

Venetoclax in combination with azacitidine in Japanese patients with acute myeloid leukaemia: phase 1 trial findings. [2021]

3. United States 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. [2023]

4. China pubmed.ncbi.nlm.nih.gov

[Efficacy of venetoclax combined azacitidine in newly diagnosed acute myeloid leukemia unfit for standard chemotherapy: a single center experience]. [2023]

5. Italy pubmed.ncbi.nlm.nih.gov

Higher-dose venetoclax with measurable residual disease-guided azacitidine discontinuation in newly diagnosed acute myeloid leukemia. [2023]

6. China 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]. [2022]

7. United States 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. [2023]

8. England 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. [2021]

9. Germany pubmed.ncbi.nlm.nih.gov

A real-world study of infectious complications of venetoclax combined with decitabine or azacitidine in adult acute myeloid leukemia. [2022]