Primary Objective:~To compare survival of patients treated with a combination of pevonedistat and azacitidine after failure of DNA methyltransferase inhibitors (DNMTi) to historical survival for patients with relapsed/refractory myelodysplastic syndrome (MDS) or myelodysplastic/ myeloproliferative overlap syndromes (MDS/MPN) who are ineligible for hematopoietic stem cell transplant (HSCT)~Secondary Objectives:~To determine the rate of hematologic improvement (HI) in patients with relapsed/refractory MDS or MDS/MPN treated with pevonedistat and azacitidine after DNMTi failure~To determine the complete remission (CR) and marrow CR rates in patients with relapsed/refractory MDS or MDS/MPN treated with pevonedistat and azacitidine after DNMTi failure~To determine the reduction of bone marrow blasts in patients with relapsed/refractory MDS or MDS/MPN treated with pevonedistat and azacitidine after DNMTi failure~Exploratory Objectives:~To correlate the mutation burden in patients with relapsed/refractory MDS or MDS/MPN with response to treatment with pevonedistat and azacitidine~To correlate genomic aberrations with rate of response and survival in relapsed/refractory MDS or MDS/MPN patients treated with pevonedistat and azacitidine~To measure the effect of pevonedistat treatment in combination with azacitidine on quality of life in patients with relapsed/refractory MDS or MDS/MPN~To define epigenetic biomarkers for pevonedistat use in relapsed/refractory MDS or MDS/MPN
This study will evaluate the treatment combination of pevonedistat and azacitidine in the setting of DNA methyltransferase inhibitor(s) failure in patients with relapsed/refractory myelodysplastic syndrome or myelodysplastic syndrome/myeloproliferative neoplasm.