A Multi-center, Randomized, Double-blind, Placebo-controlled Clinical Trial of Deferasirox in Patients With Myelodysplastic Syndromes (Low/Int-1 Risk) and Transfusional Iron Overload
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 225
- 试验地点
- 12
- 主要终点
- Event-free Survival
研究概览
简要总结
This was a randomized, double-blind trial to evaluate deferasirox vs placebo in patients with myelodysplastic syndromes (low/int-1 risk) and transfusional iron overload .The trial was conducted in 17 countries, started in 2010 and ended in 2018.
详细描述
This randomized, double blind trial to evaluate deferasirox vs placebo in patients with myelodysplastic syndromes (low/int-1 risk) and transfusional iron overload consisted of four periods, a screening period, a treatment period, a post treatment follow-up period and a survival period. The trial recruitment period lasted until December 2014 and the trial continued for three years from the date the last patient enrolled until February 2018 (last patient last visit date).
Screening period:
The screening period lasting up to 35 days with two screening visits, at least 14 days apart, used to assess patient eligibility. Eligible patients with low or int-1 risk myelodysplastic syndromes (MDS) with transfusional iron overload were randomized in a 2:1 ratio to deferasirox or placebo respectively. Randomization was also stratified using the International prognostic scoring system of low or int-1 MDS and by geographical region (Asian vs non-Asian countries) since the Asian population has been reported to have a longer survival.
The following concomitant medications could be permitted for use while the patient was on study, and information outlining start date(s) and end date(s) of each medication taken were to be recorded on the appropriate eCRF: Erythropoietin (growth factor), G-CSF (growth factor), GM-CSF growth factor), Azacitidine, Thalidomide, Arsenic trioxide, Lenalidomide, Decitabine, Cyclosporine A, Vitamin C supplements (≤ 200 mg/day)
Treatment period:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
Patients, investigator staff, persons performing the assessments, and data analysts remained blind to the identity of the study treatment from the time of randomization until database lock.
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
- •Weigh between 35-135 kilograms
- •Low or int-1 risk MDS
- •Ferritin >1000 micrograms/liter at screening
- •History of transfusion of 15 to 75 Packed Red Blood Cells (PRBC) units
- •Anticipated to be transfused with at least 8 units of PRBCs annually during the study
- •Women of child-bearing potential using effective methods of contraception during dosing of study treatment
排除标准
- •More than 6 months of cumulative ICT (such as daily deferasirox (Exjade®) or deferiprone or 5×/week deferoxamine)
- •More than 3 years since patient began receiving regular transfusions (2 units per 8 weeks or 4 units received in a 3 month period)
- •Significant proteinuria
- •History of hospitalization for congestive heart failure; other heart conditions as specified in the protocol
- •Systemic diseases which would prevent study treatment
- •Hepatitis B; Hepatitis C; HIV
- •Liver cirrhosis
- •Pregnant, or breast-feeding patients, or patients of child-bearing potential not employing an effective method of birth control
- •History of drug or alcohol abuse within the 12 months prior to enrollment
研究组 & 干预措施
Deferasirox
10 mg/kg/day (once daily) for the first 2 weeks of treatment, followed by 20 mg/kg/day (once daily) from Week 2 to End of Treatment. After 3 months of treatment at 20 mg/kg/day, the dose was allowed to be adjusted by 5 or 10 mg/kg/day up to 40 mg/kg/day based on serum ferritin responses. When a target serum ferritin level was reached (usually between 500 and 1000 µg/L), the dose could be reduced by 50% to maintain the serum ferritin within the target range.
干预措施: Deferasirox (Drug)
Placebo
10 mg/kg/day (once daily) for the first 2 weeks of treatment, followed by 20 mg/kg/day (once daily) from Week 2 to End of Treatment. After 3 months of treatment at 20 mg/kg/day, the dose was allowed to be adjusted by 5 or 10 mg/kg/day up to 40 mg/kg/day based on serum ferritin responses. When a target serum ferritin level was reached (usually between 500 and 1000 µg/L), the dose could be reduced by 50% to maintain the serum ferritin within the target range.
干预措施: Placebo (Drug)
结局指标
主要结局
Event-free Survival
时间窗: Day 1 to end of treatment period, approx. 7 years
Event-free survival was defined as the time from the date of randomization to the date of the first documented non-fatal event (worsening cardiac function, hospitalization for congestive heart failure, liver function impairment, liver cirrhosis, transformation to AML, as defined in the protocol), or death, whichever occurred first. Participants who did not experience a non-fatal event as of the time of data cut-off (end of study), as well as participants who did not experience a non-fatal event and stopped study participation before the data cut-off, were censored as specified in the protocol.
次要结局
- Time to Disease Progression(Day 1 to end of treatment period, approx. 7 years)
- Time to First Occurrence of Serum Ferritin Level >2 Times the Baseline Value at Two Consecutive Assessments (at Least Two Weeks Apart)(Day 1 to end of treatment period, approx. 7 years)
- Percentage of Participants With Significant Renal Dysfunction(Day 1 to end of treatment period, approx. 7 years)
- Percentage of Participants With Newly Occurring Moderate or Severe Neutropenia(Day 1 to end of treatment period, approx. 7 years)
- Overall Survival(Day 1 to end of treatment period, approx. 7.4 years)
- Percentage of Participants With Newly Occurring Severe Thrombocytopenia(Day 1 to end of treatment period, approx. 7 years)
- Time to Study Drug Discontinuation Due to an AE or Laboratory Abnormality(Day 1 to end of treatment period, approx. 7 years)
- Percentage of Participants With Hematologic Improvement (HI) in Terms of Erythroid Response(Day 1 to end of treatment period, approx. 7 years)
- Percentage of Participants With Newly Occurring Hypothyroidism Compared to Baseline(Day 1 to end of treatment period, approx. 7 years)
- Percentage of Participants With Worsening Glucose Metabolism Compared to Baseline(Day 1 to end of treatment period, approx. 7 years)
- Time to at Least a 10% Increase From Baseline in Left Ventricular Internal Systolic Diameter (LVISD) at Two Consecutive Assessments at Least Two Weeks Apart(Day 1 to end of treatment period, approx. 7 years)
- Percentage of Participants With Major Gastrointestinal Bleeding(Day 1 to end of treatment period, approx. 7 years)
- Time to at Least a 10% Increase From Baseline in Left Ventricular End-diastolic Internal (LVIDD) at Two Consecutive Assessments at Least Two Weeks Apart(Day 1 to end of treatment period, approx. 7 years)
- Total Number of Infections Requiring Intravenous Antimicrobials(Day 1 to end of treatment period, approx. 7 years)