Ascorbate in Myelodysplastic Syndrome

NCT07283900 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 202508099
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

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.

Conditions

Myelodysplastic Syndromes

Keywords

Vitamin C; Ascorbate; Myelodysplastic Syndrome; AIMS

Outcome Measures

Primary Outcomes (2)

• Incidence of dose-limiting toxicities (DLTs)

  Assess the safety and tolerability of intravenous (IV) high-dose ascorbate (HDA) in combination with azacitidine.

  At the end of Cycle 1 (each cycle is 28 days)

• Treatment Efficacy

  Proportion of participants achieving a complete response (CR) or partial response (PR)

  At the end of Cycle 4 (each cycle is 28 days)

Secondary Outcomes (8)

• Overall Survival (OS)

  From treatment initiation until death from any cause or up to 24 months, whichever comes first

• Event-Free Survival (EFS)

  From treatment initiation until disease progression, disease relapse, treatment failure, or death from any cause, whichever came first, assessed up to 24 months

• Transfusion Requirements

  At baseline, assessed throughout the treatment up to the end of cycle 4 (each cycle is 28 days)

• Hematologic Parameters

  At baseline, assessed throughout the treatment up to the end of cycle 4 (each cycle is 28 days)

• Composite Complete Response (cCR) Rate

  At the end of cycle 4 (each cycle is 28 days)

Study Arms (1)

High-Dose Ascorbate + Azacitidine

EXPERIMENTAL

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.

Drug: High-dose ascorbate; Drug: Azacitidine

Interventions

High-dose ascorbate 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

Also known as: Vitamin C

High-Dose Ascorbate + Azacitidine

Azacitidine DRUG

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

Also known as: Vidaza

High-Dose Ascorbate + Azacitidine

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Prajwal Dhakal: lead

Study Sites (1)

University of Iowa

Iowa City, Iowa, 52242, United States

RECRUITING

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

Ascorbic Acid; Azacitidine

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates; Aza Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Prajwal Dhakal, MD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Prajwal Dhakal, MD

CONTACT

1-319-356-4200; prajwal-dhakal@uiowa.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Assistant Professor

Study Record Dates

• First Submitted: November 19, 2025
• First Posted: December 16, 2025
• Study Start: March 11, 2026
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2029
• Last Updated: March 16, 2026

Record last verified: 2026-03

Locations

US (1)