An Optimal Dose Finding Study of N-Acetylcysteine in Patients With Myeloproliferative Neoplasms
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 27
- 试验地点
- 2
- 主要终点
- Proportion of subjects who achieve 30% reduction of MPN-SAF Total symptom score (MPN-TSS)
研究概览
简要总结
This is a phase I/II study evaluating the optimal dose of N-acetylcysteine (N-AC) in patients with myeloproliferative neoplasms (MPN).
详细描述
This is a phase I/II open-label clinical trial determining the optimal biological dose (OBD) of N-acetylcysteine in subjects with myeloproliferative neoplasms. These are subjects who have a diagnosis of essential thrombocythemia (ET), polycythemia vera (PV), or myelofibrosis (MF).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥18 years of age
- •Have a diagnosis of essential thrombocythemia (ET), polycythemia vera (PV), or myelofibrosis (MF) according to the 2016 WHO criteria
- •Has not taken interferon-alpha or a JAK inhibitor (such as ruxolitinib or fedratinib) for treatment of MPN in the past 28 days before enrollment.
- •May continue on current MPN treatment, including aspirin, hydroxyurea, or anagrelide. Therapeutic phlebotomies should continue per the patient's usual regimen.
- •Has not taken N-Acetylcysteine (N-AC) or preparations containing N-AC in the past 28 days before enrollment.
- •Baseline MPN-TSS score of ≥ 10 at the time of enrollment.
- •Peripheral blast count <10% during Screening.
- •Free of other active or metastatic malignancies other than localized skin cancer.
- •Amenable to blood draws and symptom assessments.
- •Agree to the use of contraceptives. Female subjects of childbearing potential and their male partners, or male subjects who have female partners of childbearing potential, should both use an effective contraception method during the study and continue to use contraception for 60 days after the last dose of study drug.
排除标准
- •Eastern Cooperative Oncology Group (ECOG) questionnaire score of ≥3
- •Currently pregnant or planning on being pregnant within the study period.
- •Currently breastfeeding.
- •Known uncontrolled active viral or bacterial infection.
- •Significant impairment of major organ function defined as
- •Serum creatinine clearance less than 50 ml/min (calculated with Cockroft-Gault formula).
- •Bilirubin more than 1.5 mg/dl except for Gilbert's disease. ALT or AST more than 2X upper normal limit or has radiologic evidence of liver cirrhosis.
- •Platelets < 100 × 10^9/L
- •Hgb < 10 g/dL
- •ANC < 0.75 × 10^9/L
- •Known history of allergic reaction to N-AC.
研究组 & 干预措施
Dose Level 1 (DL1)
Patients take N-Acetylcysteince 600 mg orally twice daily.
This is the starting dose level for the study.
干预措施: N-Acetylcysteine (Drug)
Dose Level 2 (DL2)
Patients take N-Acetylcysteince 1200 mg orally twice daily.
If DL1 is well tolerated, the next cohort will progress to this dose level.
干预措施: N-Acetylcysteine (Drug)
Dose Level 3 (DL3)
Patients take N-Acetylcysteince 1800 mg orally twice daily.
If DL2 is well tolerated, the next cohort will progress to this dose level.
干预措施: N-Acetylcysteine (Drug)
结局指标
主要结局
Proportion of subjects who achieve 30% reduction of MPN-SAF Total symptom score (MPN-TSS)
时间窗: 7 days prior to beginning treatment until end of treatment, average of 9 weeks.
MPN-SAF Total symptom score (MPN-TSS) is a validated tool to objectively measure the burden of symptoms associated with MPN. Baseline TSS will be defined as the average of the daily TSS of 7 consecutive days immediately prior to beginning N-AC. The end of study MPN-TSS will be defined as the average of the daily TSS of 7 consecutive days during week 8.
Optimal Biological Dose (OBD) of N-Acetylcysteine
时间窗: From the start date of treatment until 7 days after completion of treatment or removal of treatment due to disease progression, toxicity, delay of treatment, or withdrawal of treatment, whichever came first, up to 8 weeks.
Determination of the optimal biological dose (OBD) will be utilized to evaluate the safety and tolerability of N-AC as a treatment for patients with MPN. Optimal biological dose is defined as the therapeutic dose that possesses the highest efficacy probability while inducing acceptable toxicity
次要结局
未报告次要终点
研究者
Angela G. Fleischman
Associate Professor
University of California, Irvine