A Phase II Multi-center, Open Label, Randomized Study to Assess Safety and Efficacy of Two Different Schedules of Oral LDE225 in Adult Patients With Relapsed/Refractory or Untreated Elderly Patients With Acute Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 70
- 试验地点
- 2
- 主要终点
- Rate of Complete Remission (CR)
研究概览
简要总结
The study will evaluate the efficacy, safety and tolerability of two dosing schedules of LDE225 in patients with relapsed/refractory acute leukemia or elderly patients with untreated acute leukemia.
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
- 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
- •Subjects must have relapsed or primary refractory non-M3 acute myeloid leukemia or relapsed or refractory non-T-cell acute lymphoblastic leukemia or untreated acute myeloid leukemia in elderly patients.
- •Performance status of 0, 1 or 2 per WHO classification.
- •Adequate renal and liver function.
- •Adequate blood creatine kinase value (CK < 1.5ULN)
排除标准
- •Allogeneic stem cell transplantation within the last 4 months and/or active graft versus host disease requiring systemic immunosuppressant therapy, or autologous stem cell transplantation within the last 4 weeks.
- •Patient for which immediate allogeneic stem cell transplantation is the treatment of choice.
- •Pregnant or nursing (lactating) women.
- •Active CNS leukemic involvement
研究组 & 干预措施
LDE225-400
Patients who were randomized to Schedule A, and received 400 mg LDE225 twice daily for the first two weeks only and then after two weeks, received 800 mg LDE225 once daily until disease progression, toxicity, withdrawal of consent, death, discretion of the investigator or early termination of the study.
干预措施: LDE225 (Drug)
LDE225-800
Patients who were randomized to Schedule B, received 800 mg LDE225 once daily until disease progression, toxicity, withdrawal of consent, death, discretion of the investigator or early termination of the study.
干预措施: LDE225 (Drug)
结局指标
主要结局
Rate of Complete Remission (CR)
时间窗: at screening, every week up to Week 9, every 2 weeks thereafter until CR, every 4 weeks after CR up to 24 months
Complete Response (CR) was based on the International Working Group (IWG) criteria based on weekly peripheral blood count measurements and bone marrow biopsy/aspiration collection. Efficacy assessments were performed to determine CR. A treatment cycle was defined as 4 weeks. The outcome measure for the study is based on standardized response criteria as defined by the International Working Group (IWG) for AML. The IWG was established by a group of investigators interested in the design and conduct of clinical trials in acute myeloid leukemia (AML). The criteria established by this group (a set of recommendations for response assessment) are well established, endorsed by major institutions and Health Authorities, and are widely used in clinical trials. No statistical analysis was planned for this primary outcome.
Complete Remission With Incomplete Blood Count Recovery (CRi)
时间窗: within 3 days after clearance of blasts from peripheral blood (PB), monthly thereafter until CR or reappearance of blasts in the PB, after CR every other month until discontination up to 24 months
The other primary efficacy endpoint was CRi based on the International Working Group (IWG) criteria based on weekly peripheral blood count measurements and bone marrow biopsy/aspiration collection. Efficacy assessments were performed to determine CRi. A treatment cycle was defined as 4 weeks. No statistical analysis was planned for this primary outcome.
次要结局
- Overall Response Rate (ORR)(Every 8 weeks for the first 6 months and every 12 weeks until 53 weeks after the last patient is enrolled or until relapse up to 24 months)
- Parmacokintics (PK) Parameter: Cmax(Week 1 Day 1, Week 9 Day 1)
- Parmacokintics (PK) Parameter: Tmax(Week 1 Day 1,Week 9 Day 1)
- Parmacokintics (PK) Parameter: AUC0-8h(Week 1 Day 1,Week 9 Day 1)
- Parmacokintics (PK) Parameter: AUC0-24h(Week 1 Day 1,Week 9 Day 1)