Nivolumab + Chemotherapy for Acute Myeloid Leukemia

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Autoimmune disease, Transplantation history, 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 explores a new treatment combination for acute myeloid leukemia (AML) with a specific genetic mutation called TP53. It examines how well nivolumab, an immunotherapy drug, works with two chemotherapy drugs, decitabine and venetoclax, to target and destroy cancer cells. Researchers aim to understand the side effects and effectiveness of this treatment combination compared to standard approaches for this type of AML. Individuals newly diagnosed with AML and a TP53 mutation might be suitable candidates, especially if they have not yet received treatment for AML. 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 treatment combination.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic corticosteroids or other immunosuppressive medications, you may need to stop them 14 days before starting the trial treatment.

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

Research shows that using nivolumab with decitabine and venetoclax can cause some side effects, but these treatments are generally safe in certain situations. Studies have found that low-dose decitabine combined with venetoclax is safe and effective for treating high-risk acute myeloid leukemia. Patients can usually tolerate these drugs well, although some side effects may occur.

When nivolumab is added, the overall response rate increased to 44%, but more immune-related side effects were observed. These side effects occur because the treatment boosts the immune system to fight cancer. Despite the potential for more side effects, this combination shows promise in combating the disease.

It is important to note that this is early research, and the trial remains in its first phase. While there is some evidence of safety, further research is needed to fully understand all possible side effects. Always consult with a doctor about the risks and benefits before joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatment combining nivolumab, decitabine, and venetoclax for acute myeloid leukemia (AML) because it offers a novel approach compared to traditional chemotherapy alone. Nivolumab is an immune checkpoint inhibitor that helps the immune system better attack cancer cells, which is different from typical chemotherapy that directly kills cancer cells. Venetoclax targets a specific protein that cancer cells need to survive, potentially increasing the effectiveness of the treatment. This combination may enhance the body's ability to fight AML more effectively, offering hope for improved outcomes where standard treatments may fall short.

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

This trial will evaluate the combination of three drugs—nivolumab, decitabine, and venetoclax—for treating acute myeloid leukemia (AML), especially in patients with TP53 mutations. Nivolumab, which participants in this trial may receive, is a type of immunotherapy that helps the body's immune system attack cancer cells. Decitabine and venetoclax, also part of the treatment regimen, are chemotherapy drugs that stop cancer cells from growing and spreading. Studies have found that venetoclax, when used with other treatments, can improve outcomes for some AML patients. Although researchers are still studying this drug combination, early evidence suggests it could be a promising treatment for this aggressive type of leukemia. ^{1 2 3 5 6}

Who Is on the Research Team?

Alice Mims

Principal Investigator

Ohio State University Comprehensive Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed, untreated acute myeloid leukemia (AML) that has a TP53 mutation. Participants must have good organ function, controlled infection if present, no severe concurrent illness or psychiatric conditions, and agree to use contraception. Prior hypomethylating therapy for MDS is allowed.

Inclusion Criteria

My white blood cell count is less than or equal to 25,000.

I have been diagnosed with acute myeloid leukemia through tissue or cell analysis.

My kidney function, measured by GFR, is above 40 mL/min.

Exclusion Criteria

Patients with uncontrolled intercurrent illness

My leukemia affects my central nervous system only.

Patients with history of prior allogeneic transplantation. This is due to this being a pilot study with a limited number of patients

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Patients receive nivolumab, decitabine, and venetoclax for up to 3 cycles

12 weeks

Multiple visits for IV administration and monitoring

Maintenance

Patients achieving CR or CRi continue treatment with nivolumab, decitabine, and venetoclax

Ongoing every 28 days

Regular visits for IV administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Decitabine
• Nivolumab
• Venetoclax

Trial Overview The study tests the effectiveness and side effects of combining nivolumab (an immunotherapy drug), decitabine, and venetoclax in treating AML with TP53 mutations. It aims to see if this combination works better than standard treatments.

How Is the Trial Designed?

Group I: Treatment (nivolumab, decitabine, venetoclax) Experimental Treatment 3 Interventions

INDUCTION: Patients receive nivolumab IV over 30 minutes on day 15 of cycle 1 and days 1 and 15 of subsequent cycles, decitabine IV over 60 minutes on days 1-10 of induction cycle 1 (and cycles 2 and 3 if needed), and venetoclax PO QD on days 1-21. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients who achieve a CR or CRi receive nivolumab IV over 30 minutes on days 1 and 15, decitabine IV over 60 minutes on days 1-5, and venetoclax PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04277442

Study Details | NCT04277442 | Testing Nivolumab in ... This trial studies the side effects of nivolumab in combination with decitabine and venetoclax and to see how well they work in treating patients with TP53- ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12350645/

Comprehensive view on chemotherapy-free management ... Comprehensive view on chemotherapy-free management of acute myeloid leukemia by using venetoclax in combination with targeted and/or immune ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0753332224000131

Review Immunotherapies of acute myeloid leukemia This study demonstrated that decitabine plus pembrolizumab therapy was effective in patients with relapsed AML. Pembrolizumab has shown promising results in ...

4. haematologica.org haematologica.org/article/view/9775

Outcomes of relapsed or refractory acute myeloid leukemia ... VEN+HMA offers superior responses and survival in older patients with ND AML; however, patients who have R/R disease after front-line VEN+HMA display high-risk ...

5. onclive.com onclive.com/view/addition-of-relatlimab-nivolumab-to-azacitidine-venetoclax-shows-safety-early-efficacy-in-adverse-risk-frontline-aml

Addition of Relatlimab/Nivolumab to Azacitidine ... - OncLive No patients achieved a partial remission (PR) or morphologic leukemia-free state (MLFS). However, results from the relapsed/refractory AML ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8409404/

Low‐dose decitabine plus venetoclax is safe and effective as ... Low‐dose decitabine plus venetoclax is safe and effective as post‐transplant maintenance therapy for high‐risk acute myeloid leukemia and ...