PRIMARY OBJECTIVES:~I. Evaluate the safety of NY-ESO-1 vaccination (Anti-DEC-205-NY-ESO-1 fusion protein + poly-ICLC) given in combination with decitabine 20 mg/m^2 intravenously and nivolumab 3 mg/kg in patients with myelodysplastic syndrome (MDS) or low blast count acute myeloid leukemia (AML).~SECONDRY OBJECTIVES:~I. Assess immune and molecular epigenetic responses following combination therapy with nivolumab, decitabine and NY-ESO-1 fusion protein CDX-1401 (NY-ESO-1) vaccination.~TERTIARY OBJECTIVES:~I. To record the response rate (complete response, partial response and hematological improvement) in MDS or low blast count AML patients treated with the combination in order to provide descriptive characteristics.~II. To record the overall survival (OS), progression free survival (PFS) and time to AML transformation (TTT) (for patients with MDS at diagnosis) enrolled on the study.~OUTLINE:~Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 intracutaneously and poly ICLC subcutaneously (SC) on day -14, on day 15 of courses 1-4, and then on day 1 of every 4 courses thereafter. Patients also receive nivolumab intravenously (IV) over 30 minutes on days 1 and 15 and decitabine IV over 1 hour on days 1-5. Courses with nivolumab and decitabine repeat every 4 weeks in the absence of disease progression or unaccepted toxicity.~After completion of study treatment, patients are followed up at 30, 60, 90, and 180 days.
This phase I trial studies the side effects of DEC-205/NY-ESO-1 fusion protein CDX-1401, poly ICLC, decitabine, and nivolumab in treating patients with myelodysplastic syndrome or acute myeloid leukemia. DEC-205/NY-ESO-1 fusion protein CDX-1401 is a vaccine that may help the immune system specifically target and kill cancer cells. Poly ICLC may help stimulate the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as decitabine, 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. Monoclonal antibodies, such as nivolumab, may interfere with the ability of cancer cells to grow and spread. Giving DEC-205/NY-ESO-1 fusion protein CDX-1401, poly ICLC, decitabine, and nivolumab may work better in treating patients with myelodysplastic syndrome or acute myeloid leukemia.