High-dose Ascorbate (HDA) in Combination With Standard of Care Azacitidine and Venetoclax in Acute Myeloid Leukemia (AML)

Inclusion Criteria: * 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. Exclusion Criteria * Patients who have received prior therapy to treat their AML (except for cytoreductive hydroxyurea or cytarabine dose ≤ 1 g/m2 for hyperleukocytosis) * Known hypersensitivity or allergy to ascorbate, azacitidine/decitabine, or venetoclax * AML patients with the following cytogenetic/molecular aberrations are not eligible i. t(8;21)(q22;q22.1)/RUNX1::RUNX1T1 ii. inv(16)(p13.1q22) or t(16;16)(p13.1;q22)/ CBFB::MYH11 iii. bZIP in-frame mutated CEBPA without any adverse mutations iv. KMT2A rearrangement v. NPM1 or IDH1 or IDH2 or FLT3-ITD or FLT3-TKD mutation * Patients with kidney disease needing dialysis, diabetic nephropathy, renal transplant recipients, and those with history of acute or chronic oxalate nephropathy * Patients with primary hemochromatosis or transfusional iron overload as defined as persistently elevated Ferritin \> 1000 ng/mL. * Patients with type I or type II diabetes mellitus on treatment with short acting insulin who need at least a daily blood glucose monitoring test via finger stick * Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen * Other major co-morbidities as determined unsuitable per the treating physician * HIV-infection that is uncontrolled by anti-retroviral therapy. (HIV-infected patients on effective anti- retroviral therapy with undetectable viral load within 6 months are eligible for this study) * Patients with G6PD (glucose-6-phosphate dehydrogenase) deficiency * Patients who are on warfarin or other strong CYP3A4 inducer/inhibitor and cannot have a drug substitution or who decline the drug substitution