PRIMARY OBJECTIVES:~I. To obtain preliminary data regarding the safety and tolerability of decitabine and venetoclax in combination with nivolumab when given for frontline therapy in TP53 mutated acute myeloid leukemia (AML) patients.~II. To obtain preliminary data regarding the rate of complete remission (CR), complete remission with incomplete hematological recovery (CRh), and complete remission with incomplete count recovery (CRi) in TP53 mutated AML who are treated with decitabine and venetoclax in combination with nivolumab for frontline therapy.~SECONDARY OBJECTIVES:~I. To observe and record anti-tumor activity. II. To obtain preliminary data regarding progression free survival (PFS) for TP53 mutated AML patients receiving combination therapy.~III. To obtain preliminary data regarding the overall survival (OS) for TP53 mutated patients receiving this combination therapy.~IV. To obtain preliminary data regarding minimal residual disease through monitoring TP53 mutational burden prior and throughout treatment.~V. To obtain preliminary data regarding the frequency of graft versus host disease (GVHD) including veno-occlusive disease (VOD) in patients who subsequently receive allogeneic transplantation after this combination therapy.~OUTLINE:~INDUCTION: Patients receive nivolumab intravenously (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 orally (PO) once daily (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.~After completion of study treatment, patients are followed up for 3 years.
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-mutated acute myeloid leukemia. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as decitabine and venetoclax, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This study is being done to find out whether giving nivolumab, decitabine, and venetoclax is better or worse than the usual approach for TP53-mutated acute myeloid leukemia.