High-dose Ascorbate (HDA) in Combination With Azacitidine and Venetoclax (Aza/Ven) in Newly Diagnosed Acute Myeloid Leukemia (AML)
This is a randomized, open-label, Phase I clinical study with expansion. It will assess the safety and efficacy of high-dose ascorbate administered concomitantly with azacitidine and venetoclax in newly diagnosed AML.
• Adults aged ≥ 18 who are deemed unfit for intensive chemotherapy by meeting at least one of the following criteria:
‣ age ≥ 75
⁃ Eastern Cooperative Oncology Group (ECOG) performance of 2-3
⁃ Severe cardiac disorder (e.g., congestive heart failure requiring treatment, ejection fraction ≤ 50%, or chronic stable angina)
⁃ Severe pulmonary disorder (e.g., DLCO ≤ 65% or FEV1 ≤ 65%)
⁃ Creatinine clearance \< 45 mL/min
⁃ Hepatic disorder with total bilirubin \> 1.5 times the upper limit of normal
⁃ Any other comorbidity that the investigators determine to be incompatible with intensive chemotherapy
• Newly diagnosed (non-APL) acute myeloid leukemia except those with cytogenetic/molecular abnormalities in the exclusion criteria
• Participants must have adequate organ function, defined as:
‣ Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤ 3.0 x upper limit of normal (ULN)
⁃ International normalized ratio (INR) \< 1.5 x ULN and partial thromboplastin time (PTT) \< 1.5 x ULN (patient could be eligible if they respond appropriately to correction with FFP or cryoprecipitate)
• Patients with a history of antecedent myelodysplasia (MDS) are eligible if they have not had prior chemotherapy/hypomethylating agent (e.g., azacitidine or decitabine). Prior exposure to other investigational agents could be considered at PI's discretion
• Patients who have developed therapy-related AML after prior radiation or chemotherapy for other malignancy(ies) are eligible if they have not been exposed to hypomethylating agent (e.g., azacitidine or decitabine) and/or venetoclax
• Patients presenting with marked leukocytosis (WBC \> 25 k/mm3) should receive cytoreduction with hydroxyurea or cytarabine dose ≤ 1 g/m2 to mitigate the risk of tumor lysis syndrome before initiation of therapy with venetoclax
• For female participants of childbearing potential, a negative serum or urine pregnancy test (sensitivity of at least 25 mIU/mL) at screening
• Ability to understand and the willingness to sign a written informed consent document.
• Both male and female participants of childbearing potential agree to use an adequate method of contraception from screening through 6 months after the last dose of study treatment.