If you choose to join this study, you will get a random assignment (like a coin flip) to 1 of 2 groups. Group 1: If you are in this group, you will get ASTX727 as a pill you take by mouth once a day for the first 5 days of the cycle. Each cycle lasts 28 days. You will continue on treatment indefinitely if you achieve a remission or are having clinical benefit and do not go on another myeloMATCH treatment study or onto receive an allogeneic stem cell transplant. ASTX727 is a standard, approved drug for the treatment of MDS. If your disease does not have a complete remission after 6 cycles, you may be offered the opportunity to begin taking the study drug along with ASTX727. If you do take part, you will get ASTX727 as pills you take by mouth once a day for the first 5 days of the cycle and enasidenib as pills you take by mouth once a day for 28 days. Each cycle lasts for 28 days Group 1: If you are in this group, you will get the study drug plus ASTX727. You will get ASTX727 as pills you take by mouth once a day for the first 5 days of the cycle and the study drug as pills you take by mouth once a day for 28 days. Each cycle lasts 28 days. You will continue on treatment indefinitely if you achieve a remission or are having clinical benefit and do not go on another myeloMATCH treatment study or onto receive an allogeneic stem cell transplant.