NCT03920657终止2 期
Early and Low Dose Deferasirox (3.5 mg/kg FCT) to Suppress NTBI and LPI as Early Intervention to Prevent Tissue Iron Overload in Lower Risk MDS
Fondazione Italiana Sindromi Mielodisplastiche-ETS10 个研究点 分布在 1 个国家目标入组 11 人开始时间: 2019年10月4日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 11
- 试验地点
- 10
- 主要终点
- Change of hepatic iron
研究概览
简要总结
The scientific rationale for this study is the evolving understanding that iron-induced tissue damage is not only a process of progressive bulking of organs through high-volumes iron deposition, but also a reactive iron species related "toxic" damage.
Iron mediated damage can occur prior reaching high iron storage thresholds derived from thalassemia major setting, free toxic iron species being already present when transferrin saturation >60-70% (25); therefore a timely early adoption of iron chelation may be of benefit before overt iron overload is seen.
Our hypothesis is that early and low dose DFX-FCT is better tolerated and is able to prevent iron accumulation and consequently tissue iron related damage, by consistently suppressing iron reactive oxygen species (NTBI and LPI).
If this hypothesis is confirmed this approach could contribute to an improvement of clinical practice of patients managements. Additionally this approach might also be a contribute in preventing future iron overloaded related complication, in this already frail and co-treated patient population.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis: Adult Myelodysplastic Syndrome (≥18 years).
- •Revised IPSS: very low. low - intermediate
- •Having received 5-20 packed red blood cell units
- •Serum ferritin ≥300 ng/ml
- •Transferrin saturation ≥ 60%
- •Chelation naïve
- •Capability to provide informed consent
排除标准
- •Patients aged <18 years old
- •Higher risk (revised IPSS) MDS (Intermediate 2, high)
- •Cumulative transfusion story of > 20 packed red cell units
- •Creatinine Clearance (CrCL): <60 ml/min. Patients with CrCl of 40-60ml/min will be included only individually if no other renal risk factors are present.
- •Serum creatinine >2 x ULN at screening. If borderline serum creatinine will be measured within 7-10 days and the mean value will be used for eligibility criteria.
- •Significant proteinuria as indicated by a urinary protein/creatinine ratio > 0.5 mg/mg in a non-first void urine sample (or alternatively in two of three samples obtained for screening).
- •ECOG performance status >
- •Left ventricular ejection fraction < 50% by echocardiography
- •A history of repeated hospitalization for congestive heart failure.
- •Systemic diseases that would prevent study treatment (e.g. uncontrolled hypertension, cardiovascular, renal, hepatic, metabolic, etc.)
- •Clinical or laboratory evidence of chronic Hepatitis B or Hepatitis C (definition of chronic hepatitis follows EASL 2017 criteria).
- •History of HIV positive test result (ELISA or Western blot).
- •Treatment with systemic investigational drug within 4 weeks or topical investigational drug within 7 days of study start.
- •ALT or AST over 3 times superior to ULN at screening.
- •ANC < 500/ microL
- •Platelets transfusion dependency
- •Total bilirubin over 1.5 times superior to ULN at screening (patients with Gilbert syndrome are allowed to enter the study)
- •Diagnosis of Child score C liver cirrhosis.
- •Patients participating in another clinical trial other than an observational registry study.
- •Patients with a history of another malignancy within the past 3 years, with the exception of basal skin carcinoma or cervical carcinoma in situ or completely resected colonic polyps carcinoma in situ.
- •History of non-compliance to medical regimens, or patients who are considered potentially unreliable and/or not cooperative.
- •Presence of a surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of study drug.
- •Pregnant, intending-to-become pregnant, or breast-feeding patients.
- •Women of potential maternity age who do not agree to practice effective contraceptive methods fo the entire study duration.
- •History of drug or alcohol abuse within the 12 months prior to enrollment.
- •Hypersensitivity to the active substance or to any of the excipients.
- •Inability to provide a valid informed consent
研究组 & 干预措施
Deferasirox
Experimental
patients will be assigned to a fixed dose of 3.5 mg/kg/day of DFX FCT.
干预措施: Deferasirox (Drug)
结局指标
主要结局
Change of hepatic iron
时间窗: 1 year
Change of hepatic iron from the baseline according to baseline hepatic iron level: For patients with baseline LIC ≤5 mg/g dry weight (dw) ± 1.5 mg/g dw. For patients with baseline LIC \>5 mg/g dw ±20%
次要结局
- Efficacy of treatment(1 year)
- Evolution of toxic serum iron forms(1 year)
- Hemopoietic response(1 year)
- Costs analysis(1 year)
- Definition of iron overload(1 year)
- Relationship between NTBI and LPI with serum ferritin and liver and pancreas iron overload(1 year)
- Leukemic transformation(1 year)
- Study of biological cellular damage(1 year)
- Evolution of iron overload serologic markers(1 year)
- Overall safety of deferasirox(1 year)
研究者
研究点 (10)
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