A Phase II Trial of High Dose Ascorbate in Combination With Azacitidine in Adults With Myelodysplastic Syndrome
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 38
- 试验地点
- 1
- 主要终点
- Incidence of dose-limiting toxicities (DLTs)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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-
- •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.
排除标准
- •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).
研究组 & 干预措施
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.
干预措施: High-dose ascorbate (Drug)
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.
干预措施: Azacitidine (Drug)
结局指标
主要结局
Incidence of dose-limiting toxicities (DLTs)
时间窗: At the end of Cycle 1 (each cycle is 28 days)
Assess the safety and tolerability of intravenous (IV) high-dose ascorbate (HDA) in combination with azacitidine.
Treatment Efficacy
时间窗: At the end of Cycle 4 (each cycle is 28 days)
Proportion of participants achieving a complete response (CR) or partial response (PR)
次要结局
- 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))
- Overall Response Rate (ORR)(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)(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(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))
研究者
Prajwal Dhakal
Clinical Assistant Professor
University of Iowa