High-dose IV vitamin C plus azacitidine for higher-risk myelodysplastic syndrome

A Phase II Trial of High Dose Ascorbate in Combination With Azacitidine in Adults With Myelodysplastic Syndrome

This trial will try adding high-dose IV vitamin C to azacitidine for adults with higher-risk MDS to see if it improves treatment response and is safe.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 38 (estimated)
• Ages: 18 Years to 99 Years
• Sex: All
• Sponsor: University of Iowa (Academic / other)
• Drugs / interventions: prednisone
• Locations: 1 site (Iowa City, Iowa)
• Trial ID: NCT07283900 on ClinicalTrials.gov

What this trial studies

This open-label Phase II trial enrolls 38 adults with higher-risk myelodysplastic syndrome and begins with a small safety run-in followed by an efficacy phase. Participants receive high-dose intravenous ascorbate together with standard azacitidine and are closely monitored for safety, tolerability, and hematologic responses. Eligible patients include those with IPSS-M moderate high to very high risk, ECOG 0–2, adequate organ function, and minimal prior HMA exposure. Primary outcomes include adverse events and response rates to determine whether ascorbate adds benefit to azacitidine therapy.

Who should consider this trial

Good fit: Adults (≥18) with higher-risk MDS per IPSS-M who need hypomethylating-agent therapy, have ECOG 0–2, adequate organ function, and limited prior MDS-directed therapy (≤1 prior HMA cycle) are ideal candidates.

Not a fit: Patients with isolated del(5q) eligible for lenalidomide, MDS/MPN overlap syndromes, extensive prior MDS therapy, or significant organ dysfunction are unlikely to receive benefit from this approach.

Why it matters

Potential benefit: If successful, adding high-dose IV vitamin C could increase response rates to azacitidine and help delay progression of higher-risk MDS.

How similar studies have performed: Preclinical data and small clinical reports suggest vitamin C can modulate epigenetics and may enhance hypomethylating agents, but robust clinical evidence for this combination in MDS is limited.

Eligibility criteria

Inclusion Criteria

* Age ≥ 18 years.
* Diagnosis of myelodysplastic syndrome (MDS) requiring treatment with a hypomethylating agent (HMA).
* Higher-risk MDS per the Molecular International Prognostic Scoring System (IPSS-M) - Moderate High, High, or Very High risk categories.
* No prior MDS-directed therapy, except:

  ≤ 1 prior cycle of azacitidine, decitabine, or oral decitabine-cedazuridine; or prior use of ESA, luspatercept, or imetelstat. Prior hydroxyurea use is allowed but continuation beyond Cycle 1 requires PI approval.
* ECOG performance status 0-2.
* Adequate organ function: Creatinine clearance \>45 mL/min; total bilirubin ≤1.5 × ULN; ALT and AST ≤3 × ULN.
* Ability to provide written informed consent.
* Willingness to comply with study visits, treatment, and contraception requirements.
* Negative pregnancy test for women of childbearing potential at screening.

Exclusion Criteria

* MDS with isolated del(5q) eligible for lenalidomide therapy.
* MDS/MPN overlap syndromes other than MDS.
* Known hypersensitivity or allergy to ascorbate or azacitidine.
* Pregnant or nursing individuals.
* Inability or unwillingness to use adequate contraception.
* Uncontrolled intercurrent illness including active infection, recent myocardial infarction (≤6 months), uncontrolled heart failure or arrhythmia, pulmonary edema, unstable angina, or significant psychiatric illness.
* Renal disease requiring dialysis, diabetic nephropathy, renal transplant recipients, or history of oxalate nephropathy.
* Paroxysmal nocturnal hemoglobinuria.
* Uncontrolled HIV infection (patients on effective antiretroviral therapy with undetectable viral load within 6 months are eligible).
* G6PD deficiency.
* Use of warfarin (due to potential interaction with high-dose ascorbate).
* Diabetic patients using fingerstick or continuous glucose monitors to adjust insulin doses (ascorbate can cause false readings).
* Concurrent active malignancy, except adequately treated nonmelanoma skin cancer or curatively treated in situ cancers with \>2 years disease-free.
* Systemic immunosuppressive therapy with prednisone ≥20 mg/day (or equivalent), except for inhaled or topical steroids.
* Primary hemochromatosis or transfusion-related iron overload (ferritin \>1000 ng/mL).

Where this trial is running

Iowa City, Iowa

• University of Iowa — Iowa City, Iowa, United States (Recruiting)

Study contacts

• Principal investigator: Prajwal Dhakal, MD — University of Iowa
• Study coordinator: Prajwal Dhakal, MD

Conditions Myelodysplastic Syndromes; Vitamin C; Ascorbate; Myelodysplastic Syndrome; AIMS