To find the recommended dose of ropeginterferon alfa-2b in combination with azacitidine in patients with newly diagnosed MDS/AML with TP53 mutations. To learn if the recommended dose of ropeinterferon alfa-2b found in Dose Escalation in combination with azacitidine can help to control the disease.

Primary Objectives To evaluate the safety and to determine the recommended phase 2 dose of rope interferon in combination with AZA.

Eligibility Criteria

Participants with following:

i) Adult participants (≥ 18 years) with newly diagnosed MDS/AML ≥ 10% blasts with TP53 aberration

• TP53 aberration defined by:

  • Single TP53 mutation> 10% VAF
  • ≥ 1 mutation of any VAF, irrespective of cytogenetics or TP53 allele loss
  • Single TP53 mutation 5-10% with complex karyotype and/or TP53 allele loss

• (TP53 mutation will include any known pathogenic missense, truncating or splicing mutations (defined as Tier 1 or 2 in the UT MD Anderson CLIA lab myeloid NGS panel or validated by molecular pathologist; TP53 allele loss on FISH should be at least > 5%) ii) Ineligible for intensive chemotherapy

  • Adult participants ≥ 60 years of age, OR

  • Adult participants 18 to 60 years of age with at least one of the following relevant clinical situations/status:

  • Eastern cooperative oncology group (ECOG) performance status ≥2

  • Clinically significant organ comorbidities, as reflected by at least 1 of:

    • Left ventricular ejection fraction (LVEF) \