Phase II De-Escalation Study of Metronomic Decitabine/Cedazuridine Plus Venetoclax in AML

Prior treatment

• Progression or relapse after induction standard HMAs + Venetoclax therapy
• Uncontrolled infection, active CNS disease, or concurrent malignancy requiring systemic therapy
• Candidate for intensive chemotherapy
• Uncontrolled infection, active CNS disease, or concurrent malignancy requiring systemic therapy
• Candidate for stem cell transplant

Other illness

• Inability to take oral medication or presence of malabsorption syndrome or any other uncontrolled gastrointestinal condition

Other

• Pregnancy or breastfeeding

• Newly diagnosed AML (WHO 2022 classification or ICC 2022 classification)
• Participants must be considered Ineligible for intensive induction defined by the following:
  • Age 75 years or older, or
  • Age 18 to 74 years with at least one of the following comorbidities:
  • Severe cardiac disorder (eg, congestive heart failure requiring treatment, ejection fraction ≤50%, or chronic stable angina). ii) Severe pulmonary disorder (eg, DLCO ≤65% or FEV1 ≤65%). iii) Creatinine clearance ≥30 mL/min to \<45 mL/min iv) Moderate hepatic impairment with total bilirubin \>1.5 to ≤3.0 × upper limit of normal (ULN).
• Must have achieved CR,CRh, CRi, following induction with maximum 3 cycles of standard IV HMAs and venetoclax.
• Able to provide informed consent
• Prior and concomitant hydroxyurea is permitted
• ECOG performance status 0 to 3