Vitamin C (High Dose Ascorbate) with Azacitidine for the Treatment of Myelodysplastic Syndrome

Inclusion Criteria

• Age ≥ 18 years
• New or an established diagnosis of MDS requiring treatment with hypomethylating agents (HMAs): * Higher risk MDS per Molecular International Prognostic Scoring System for Myelodysplastic Syndromes (IPSS-M) ** Moderate high, High, or Very high
• No prior MDS-directed therapies, including lenalidomide. * Exception: Received ≤ 1 cycle of azacitidine, decitabine, or oral decitabine cedazuridine; erythropoiesis-stimulating agents (ESA), luspatercept; imetelstat. * NOTE: Prior exposure to hydroxyurea is permitted. * Continuation of hydroxyurea beyond the first cycle must be discussed with the principal investigator (PI)
• Ability to understand and be willing to provide written informed consent
• Willing and able to comply with the scheduled study visits and follow-ups, treatment plans, laboratory tests, use of 2 methods of birth control, and other procedures
• Creatinine clearance > 45 ml/min using the Cockcroft-Gault formula
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
• Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 3 x ULN
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2
• Negative serum/high-sensitivity urine pregnancy test (for women of childbearing potential) that is negative at the screening visit

Exclusion Criteria

• MDS with isolated 5q deletion that are candidates for lenalidomide treatment
• MDS/myeloproliferative neoplasm (MPN) overlap syndromes other than MDS
• Known hypersensitivity or allergy to ascorbic acid or azacitidine
• Any of the following: * Pregnant individuals * Nursing individuals * Individuals of childbearing potential who are unwilling to use adequate contraception
• Co-morbid or concurrent conditions that, in the investigator's judgment, would make the patient unsuitable for enrollment in this study or significantly interfere with the accurate assessment of the safety and toxicity of the treatment regimen
• Uncontrolled intercurrent illness, including but not limited to ongoing or active infection, myocardial infarction (≤ 6 months), current symptomatic congestive heart failure or known left heart ejection fraction (LVEF) < 40%, pulmonary congestion or pulmonary edema, clinical dehydration, unstable angina pectoris/angina equivalent, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Patients with kidney disease needing dialysis, diabetic nephropathy, renal transplant recipients, and those with history of acute or chronic oxalate nephropathy
• Patients with paroxysmal nocturnal hemoglobinuria
• HIV infection is uncontrolled by anti-retroviral therapy (Patients on effective anti-retroviral therapy with an undetectable viral load within 6 months are eligible)
• Patients with G6PD deficiency
• Diabetic patients who rely on fingerstick or continuous glucose monitoring devices to guide their insulin doses since ascorbate can interfere with glucometer readings
• Patients receiving warfarin
• Concurrent active malignancy, except adequately treated nonmelanoma skin cancer. A history of curatively treated in situ cancer of the cervix, curatively treated in situ cancer of the breast, or other solid tumors that have been curatively treated is allowed if there is no evidence of disease for > 2 years
• Disease requiring systemic treatment with systemic immunosuppression involving steroids at a dose of ≥ 20 mg/day prednisone (or equivalent). * Exceptions include intermittent use of bronchodilators or inhaled steroids, local steroid injections, and topical treatment steroids
• Primary hemochromatosis or patients with transfusion related iron overload as defined as persistently elevated ferritin > 1000 ng/mL