A One Year, Open Label, Multicenter Trial of LBH589 Alone or in Combination With ESA in Red Blood Cell Transfusion-dependent LOW and INT-1 MDS Patients Being Either Refractory to ESA or With a Low Probability of Response - the GErman PAnobinostat Low Risk MDS Trial - GEPARD Study
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 34
- 试验地点
- 1
- 主要终点
- Percentage of Participants With Hematological Response of the Erythropoetic System (HI-E) - Core Phase
研究概览
简要总结
This study assessed the efficacy and safety of LBH589 as single agent and in combination with ESA in red blood cell transfusion-dependent Low and Int-1 MDS patients being either refractory to ESA or with a low probability of response. The study had a non-randomized core phase followed by a randomized phase.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Patients with a lower risk MDS (LOW or INT-1 according to IPSS)
- •Red blood cell transfusion dependency of at least 4 Units/8 weeks.
- •Not responding to Erythropoietin stimulating agents (ESA) or having a low chance to do so
- •Age-adjusted normal cardiac, kidney, liver function
排除标准
- •Concomitant use of ESA
- •Concomitant use of any other investigational drug
- •Other malignancy that is not in remission for at least 1 year
- •Platelet Count < 75 x 109/L
- •Impaired cardiac function or clinically significant cardiac diseases
研究组 & 干预措施
LBH589
During the core phase, all participants received oral LBH589 40 mg (30 mg after a protocol amendment) for 4 months. During the randomization phase, participants with hematological improvement of the erythropoetic system (HI-E) and participants with stable disease, who were randomized to single agent LBH589, continued on single agent LBH589 40mg/30mg for an additional 4 months.
干预措施: LBH589 (Drug)
LBH589 + Epoetin Alfa
During the randomized phase, participants randomized to LBH589 + Epoetin Alfa (ESA) received oral LBH589 40mg/30mg + ESA 30000 international units (IU)/week injected subcutaneously for 4 months.
干预措施: LBH589 (Drug)
LBH589 + Epoetin Alfa
During the randomized phase, participants randomized to LBH589 + Epoetin Alfa (ESA) received oral LBH589 40mg/30mg + ESA 30000 international units (IU)/week injected subcutaneously for 4 months.
干预措施: Epoetin Alfa (Drug)
结局指标
主要结局
Percentage of Participants With Hematological Response of the Erythropoetic System (HI-E) - Core Phase
时间窗: 16 weeks
HI-E was assessed according to the modified international working group (IWG) criteria for HI. Erythroid response (pretreatment, \<11 g/dL): Hgb increase by ≥ 1.5 g/dL, relevant reduction of units of RBC transfusions by an absolute number of at least 4 RBC transfusions/8 wk compared with the pretreatment transfusion number in the previous 8 wk, and only RBC transfusions given for a Hgb of ≤ 9.0 g/dL pretreatment were counted in the RBC transfusion response evaluation; Platelet response (pretreatment, \< 100 x 109/L): absolute increase of ≥ 30 x 109/L for participants starting with \> 20 x 109/L and platelets Increase from \< 20 x 109/L to \> 20 x 109/L and by at least 100%; Neutrophil response (pretreatment, \< 1.0 x 109/L): at least 100% increase and an absolute increase \> 0.5 x 109/L; Progression or relapse after HI: At least 1 of the following: At least 50% decrement from maximum response levels in granulocytes or platelets, reduction in Hgb by ≥1.5 g/dL, or transfusion dependence.
次要结局
- Frequency Distribution of IPSS Score Status - Randomized Phase(52 weeks)
- Time to Response - Overall Period(52 weeks)
- Overall Survival (OS) - Overall Period(48 weeks)
- Percentage of Participants With Objective Response During the Randomized Phase(32 weeks, 48 weeks)
- Frequency Distribution of IPSS Score Status - Core Phase(baseline)
- Event-free Survival (EFS) - Overall Period(52 weeks)
- Disease-free Survival (DFS) - Overall Period(52 weeks)
- Time to Cause-specific Death - Overall Period(52 weeks)
- Percentage of Participants With HI-E - Randomized Phase(32 weeks, 52 weeks)
- Mean Single Scoring Values of the IPSS - Core Phase(baseline)
- Mean Single Scoring Values of the IPSS - Randomized Phase(52 weeks)
- Progression-free Survival (PFS) - Overall Period(52 weeks)
- Percentage of Participants With Objective Response During Core Phase(16 weeks)