Ascorbate in Myelodysplastic Syndrome (AIMS)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Myelodysplastic Syndromes
• Intervention / Treatment: Drug: High-dose ascorbate; Drug: Azacitidine

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.

• Study Type: Interventional
• Enrollment (Estimated): 38
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Prajwal Dhakal, MD; Phone Number: 1-319-356-4200; Email: prajwal-dhakal@uiowa.edu

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Drug: 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; Other Names: Vitamin C; 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; Other Names: Vidaza

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Time from treatment initiation to death from any cause.	From treatment initiation until death from any cause or up to 24 months, whichever comes first
Event-Free Survival (EFS)	Time from treatment initiation to progression, relapse, treatment failure, or death.	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	Changes in red blood cell and platelet transfusion needs during treatment.	At baseline, assessed throughout the treatment up to the end of cycle 4 (each cycle is 28 days)
Hematologic Parameters	Changes in hemoglobin, platelet, and neutrophil counts.	At baseline, assessed throughout the treatment up to the end of cycle 4 (each cycle is 28 days)
Composite Complete Response (cCR) Rate	Proportion of participants achieving CR, CRh, CRL, or CR-equivalent per IWG 2023 criteria.	At the end of cycle 4 (each cycle is 28 days)
Overall Response Rate (ORR)	Proportion of participants achieving CR, CRh, CRL, PR, or hematologic improvement (HI) per IWG 2023 criteria after four treatment cycles	At the end of cycle 4 (each cycle is 28 days)
Health-Related Quality of Life (HRQOL) Using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)	HRQOL will be assessed using the EORTC QLQ-C30 questionnaire. This outcome measure will evaluate participants' overall quality of life, functional status, and symptom burden at various time points throughout the study. Scoring Range: 0 to 100 for each scale. Functioning Scales: Higher scores = better functioning. Symptom Scales: Higher scores = worse symptoms. Global Health Status/QOL Scale: Higher scores = better overall QOL.	At baseline, at the end of cycle 4, every 3 months after the end of cycle 4 up to 24 months (each cycle is 28 days)
Health-Related Quality of Life (HRQOL) using EuroQol (EQ-5D-5L) questionnaire	HRQOL will be assessed using the EQ-5D-5L questionnaire, which uses a descriptive system and a visual analogue scale. The descriptive system will evaluate participants' mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Scoring range: 11111 to 55555. Higher scores= worse problems. The visual analog scale asks patients to rate their current health on a scale of 0 to 100. Higher scores= better health status.	At baseline, at the end of cycle 4, every 3 month after end of cycle 4 up to 24 months (each cycle is 28 days)

Collaborators and Investigators

• Sponsor: Prajwal Dhakal
• Investigators: Principal Investigator: Prajwal Dhakal, MD, University of Iowa

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2026
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2029

Study Registration Dates

• First Submitted: November 19, 2025
• First Submitted That Met QC Criteria: December 11, 2025
• First Posted (Actual): December 16, 2025

Study Record Updates

• Last Update Posted (Actual): March 16, 2026
• Last Update Submitted That Met QC Criteria: March 12, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Vitamin C; Myelodysplastic Syndrome; Ascorbate; AIMS
• Additional Relevant MeSH Terms: Hematologic Diseases; Bone Marrow Diseases; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Carbohydrates; Sugar Acids; Acids, Acyclic; Carboxylic Acids; Hydroxy Acids; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Aza Compounds; Nucleosides; Ribonucleosides; Azacitidine; Ascorbic Acid
• Other Study ID Numbers: 202508099

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes