Ascorbate in Myelodysplastic Syndrome

NCT ID: NCT07283900

Last Updated: 2025-12-16

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-05-01
• Study Completion Date: 2029-05-01

Brief Summary

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.

Detailed 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.

Conditions

Myelodysplastic Syndromes

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

High-Dose Ascorbate + Azacitidine

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.

Group Type: EXPERIMENTAL

High-dose ascorbate

Intervention Type: DRUG

Ascorbate, or vitamin C, is a water-soluble vitamin with antioxidant properties that also functions as a cofactor for several enzymatic reactions, including collagen synthesis and the activity of dioxygenase enzymes involved in DNA and histone demethylation

Azacitidine

Intervention Type: DRUG

Azacitidine is a pyrimidine nucleoside analog of cytidine that incorporates into RNA and DNA, inhibiting DNA methyltransferase and leading to global DNA hypomethylation

Interventions

High-dose ascorbate

Ascorbate, or vitamin C, is a water-soluble vitamin with antioxidant properties that also functions as a cofactor for several enzymatic reactions, including collagen synthesis and the activity of dioxygenase enzymes involved in DNA and histone demethylation

Intervention Type: DRUG

Azacitidine

Azacitidine is a pyrimidine nucleoside analog of cytidine that incorporates into RNA and DNA, inhibiting DNA methyltransferase and leading to global DNA hypomethylation

Intervention Type: DRUG

Other Intervention Names

Vitamin C; Vidaza

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Prajwal Dhakal

OTHER

Sponsor Role: lead

Responsible Party

Prajwal Dhakal

Clinical Assistant Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Prajwal Dhakal, MD

Role: PRINCIPAL_INVESTIGATOR

University of Iowa

Locations

University of Iowa

Iowa City, Iowa, United States

Countries

United States

Central Contacts

Prajwal Dhakal, MD

Role: CONTACT

prajwal-dhakal@uiowa.edu

1-319-356-4200

Other Identifiers

202508099

Identifier Type: -

Identifier Source: org_study_id