• Age \>= 18 years as myelodysplastic syndrome (MDS) is a very rare disease in the pediatric setting

• Diagnosis of MDS or chronic myelomonocytic leukemia (CMML) according to World Health Organization (WHO) and:

‣ MDS with int-1, int-2, or high risk by International Prognostic Scoring System (IPSS), or CMML-1/CMML-2 , myeloproliferative CMML (white blood cell \[WBC\] \>= 13 x 10\^9/L) or CMML-0 with high-risk molecular features (known mutations in ASXL1, SETBP1, RUNX1, NRAS, TP53 or more than 3 mutations).

⁃ No response after 6 cycles of azacitidine, decitabine, guadecitabine, ASTX030 or ASTX727 or relapse or progression after any number of cycles

• Serum creatinine =\< 1.5 x upper limit of normal (ULN) OR creatinine clearance \>= 50 ml/min for patients with creatinine levels \> 1.5 x ULN

• Adequate hepatic function with total bilirubin \< 2 x ULN (will allow less than 5 x ULN if Gilbert's syndrome at investigator's discretion)

• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =\< 3 x ULN

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

• Patient (or patient's legally authorized representative) must have signed an informed consent document indicating that the patient understands the purpose of and procedures required for the study and is willing to participate in the study

• Prior hydroxyurea for control of leukocytosis or use of hematopoietic growth factors (e.g., granulocyte colony-stimulating factor \[G-CSF\], granulocyte-macrophage colony-stimulating factor \[GM-CSF\], Procrit, Aranesp, thrombopoietins) is allowed at any time prior to or during study if considered to be in the best interest of the patient