Testing Nivolumab in Combination With Decitabine and Venetoclax in Patients With Newly Diagnosed TP53 Gene Mutated Acute Myeloid Leukemia

Inclusion Criteria

• Patients must have histologically or cytologically confirmed acute myeloid leukemia (AML)
• Presence of TP53 mutation at diagnosis
• Newly diagnosed, untreated AML
• Patients who received prior hypomethylating therapy for a prior myelodysplastic syndrome (MDS) diagnosis are allowed
• Eastern Cooperative Oncology Group (ECOG) performance status = = 60%)
• Total bilirubin = 40 mL/min/1.73 m^2
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association functional classification. To be eligible for this trial, patients should be class 2B or better. A baseline troponin should be within normal limits and baseline oxygen saturation should be greater than or equal to 92%. A baseline electrocardiogram (ECG) should be normal, or with stable changes if patient has chronic ECG changes
• Active infection is permitted if the infection is under control
• White blood count (WBC) must be = 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses = = 100,000 with symptoms of leukostasis)
• Isolated extramedullary leukemia of central nervous system (CNS) involvement with leukemia
• Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the exception of alopecia
• Patients who are receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to decitabine, venetoclax, or nivolumab
• Patients with uncontrolled intercurrent illness
• Patients with psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study because fetal risk has been demonstrated with decitabine with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with decitabine, breastfeeding should be discontinued if the mother is treated with decitabine. These potential risks may also apply to other agents used in this study