Ascorbate in Myelodysplastic Syndrome

Official title

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

Overview

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.

Interventions

• 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
• 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

Primary outcome measures

• Incidence of dose-limiting toxicities (DLTs) [Time frame: At the end of Cycle 1 (each cycle is 28 days)]
• Treatment Efficacy [Time frame: At the end of Cycle 4 (each cycle is 28 days)]

Secondary outcome measures (8)

• Overall Survival (OS) [Time frame: From treatment initiation until death from any cause or up to 24 months, whichever comes first]
• Event-Free Survival (EFS) [Time frame: 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 [Time frame: At baseline, assessed throughout the treatment up to the end of cycle 4 (each cycle is 28 days)]
• Hematologic Parameters [Time frame: At baseline, assessed throughout the treatment up to the end of cycle 4 (each cycle is 28 days)]
• Composite Complete Response (cCR) Rate [Time frame: At the end of cycle 4 (each cycle is 28 days)]
• Overall Response Rate (ORR) [Time frame: 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) [Time frame: 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 [Time frame: 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)]

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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• University of Iowa — Iowa City

Identifiers

NCT: NCT07283900 · 202508099

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗