Ascorbate in Myelodysplastic Syndrome (AIMS)

Prajwal Dhakal

Status and phase: Begins enrollment in 2 months; Phase 2

Conditions: Myelodysplastic Syndromes

Treatments: Drug: Azacitidine; Drug: High-dose ascorbate

Study type: Interventional

Funder types: Other

Identifiers

NCT07283900

202508099

Details and patient eligibility

About

This is an open-label, phase II clinical trial with safety run-in evaluating the safety, tolerability, and efficacy of IV HDA in combination with azacitidine for participants with MDS.

Full description

This Phase II clinical trial investigates the combination of high-dose intravenous ascorbate (vitamin C) with azacitidine in adults with higher-risk myelodysplastic syndrome (MDS). The study includes a small safety run-in followed by an efficacy phase, enrolling a total of 38 participants. It aims to determine whether adding high-dose ascorbate can safely enhance the therapeutic response to azacitidine, a standard hypomethylating agent used in MDS treatment.

Enrollment: 38 estimated patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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).

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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38 participants in 1 patient group

High-Dose Ascorbate + Azacitidine

Experimental group

Description:

All participants receive the combination of high-dose intravenous ascorbate (75 g on days 1, 3, 5, and 7) and azacitidine (75 mg/m² intravenous or subcutaneous on days 1-7) in 28-day treatment cycles.

Treatment:

Drug: High-dose ascorbate

Drug: Azacitidine