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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
8
Given intracutaneously
Given IV
Correlative studies
Given IV
Given SC
Roswell Park Cancer Institute
Buffalo, New York, United States
Incidence of adverse events
Will evaluate the proportion of n=12 evaluable patients in the expansion cohort experiencing a dose-limiting toxicity. Toxicity rates will be described using upper 1-sided 95% Jeffreys binomial confidence intervals.
Time frame: Up to 180 days
Immune cell profile
Descriptive statistics will be used to evaluate the Immune cell profile in the peripheral blood and bone marrow following combination therapy using mass cytometry.
Time frame: Up to 180 days
Peripheral blood and bone marrow cells responses
Will determine the impact of combination treatment on peripheral blood and bone marrow cells from patients treated in this manner on NY-ESO-1 target gene expression, NY-ESO-1 protein expression, NY-ESO-1 promoter methylation, and global deoxyribonucleic acid (DNA) methylation. The statistical significance of the change in marker values resulting from treatment will be assessed using the (paired sample) Wilcoxon Signed Rank test.
Time frame: Up to 180 days
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.