A Randomized, Double-blind, Placebo-controlled, Japan Local Phase II Clinical Study Comparing Eltrombopag Monotherapy Versus Placebo in Adult Lower-risk Myelodysplastic Syndromes (MDS) Patients With Platelet Transfusion Dependence
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Percentage of participants who achieve platelet transfusion independence at Week 24
研究概览
简要总结
This study is designed to evaluate the efficacy and safety of eltrombopag monotherapy in Japanese adult patients with platelet transfusion-dependent lower-risk Myelodysplastic syndromes (LR-MDS).
详细描述
This is a randomized, double-blind, placebo-controlled, Japanese local phase II study to evaluate the efficacy and safety of eltrombopag monotherapy in Japanese adult patients with platelet transfusion-dependent lower-risk MDS (IPSS-R very low, low, intermediate risk with bone marrow blast count < 5% and cytogenetic very good, good or intermediate risk). Platelet transfusion dependence at baseline is defined as receiving platelet transfusion regularly with a frequency of 2 or more times within 4 weeks prior to randomization. Platelet transfusion should be performed for a patient with platelet counts < 20 X 10^9/L, or with hemorrhagic symptoms and platelet counts < 30 X 10^9/L.
The primary objective is to demonstrate superiority of eltrombopag versus placebo in terms of the proportion of participants who achieve platelet transfusion independence at Week 24.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Participants, investigators, site staffs and site monitors will remain blinded to the identity of the treatment from the time of randomization until database lock for final analysis, and the clinical study team members and anyone involved in the Japan registration activities will be blinded until database lock for the primary analysis. Randomization data are kept strictly confidential until the time of unblinding and will not be accessible by anyone else involved in the study with the following exceptions: DMC members and who will perform data analysis for DMC.
入排标准
- 年龄范围
- 20 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients diagnosed with MDS according to the WHO classification revised 4th edition by investigator assessment with one of the following prognostic risk categories, based on the International
- •Prognostic Scoring System (IPSS-R):
- •very low (0-1.5)
- •low (2-3)
- •intermediate risks (3.5-4.5) All following criteria for prognostic variables per IPSS-R should be met.
- •Bone marrow blast < 5% (per both investigator's assessment and central review)
- •Cytogenetic very good, good or intermediate risk corresponding to IPSS-R
- •Platelet transfusion dependence
- •Refractory, intolerant to, or ineligible for MDS treatments
- •Eastern Cooperative Oncology Group (ECOG) Performance status (PS) 0 or 1
排除标准
- •Patients with a history of prior administration of eltrombopag, romiplostim, or other TPO-RA
- •Therapy-related MDS per WHO classification revised 4th edition
- •MDS/myeloproliferative neoplasms including chronic myelomonocytic leukaemia per the WHO classification revised 4th edition
- •MDS with excess blasts (EB) per WHO classification revised 4th edition
- •Known history of IPSS-R high or very high risk MDS
- •Currently receiving treatments for MDS (e.g., HMA, cyclosporine A (CsA) or lenalidomide). Supportive treatment with erythropoiesis-stimulating agents (ESAs) in anemic patients or granulocyte-colony stimulating factor (G-CSF) in patients with severe neutropenia and recurrent infections is allowed if at stable dosage for 3 months prior to screening and continued at the same dosing/schedule until the optimal dose of eltrombopag has been established.
- •Patients scheduled for hematopoietic stem cell transplantation
- •Bone marrow fibrosis that leads to an inability to aspirate adequate bone marrow sample
- •Known thrombophilic risk factors (except in cases where potential benefits of participating in the study outweighed potential risks of thromboembolic events(TEE), as determined by the investigator)
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Eltrombopag Arm
Participants randomized to a 1: 1 ratio will take eltrombopag.
干预措施: Eltrombopag (Drug)
Placebo Arm
Participants randomized to a 1: 1 ratio will take Placebo.
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of participants who achieve platelet transfusion independence at Week 24
时间窗: Week 24
Platelet transfusion independence is defined as the absence of platelet transfusion for at least 8 weeks. Platelet count should be higher than the baseline count.
次要结局
- Percentage of hematologic improvement-erythroid and -neutrophil(Week 24, Year 1, Year 2)
- Percentage of participants with platelet transfusion frequency reduction at Week 24(Week 24)
- Duration of platelet response(Week 24, Year 1, Year 2)
- Percentage of participants with disease progression excluding relapse after HI(Week 24, Year 1, Year 2)
- Percentage of participants with relapse after HI and transfusion independence(Week 24, Year 1, Year 2)
- Clinically significant bleeding events(Week 24, Year 1, Year 2)
- Time to platelet transfusion independence(Year 1, Year 2)
- Duration of platelet transfusion independence(Year 1, Year 2)
- Percentage of participants with progression to Acute myeloid leukemia (AML)(Week 24, Year 1, Year 2)
- Leukemia free survival (LFS)(Week 24, Year 1, Year 2)
- Trough concentrations of eltrombopag at steady state(Intensive: pre-dose, 1, 2, 4, 6, 8, and 24 hours post-dose. Trough: 15th days after starting the initial dose or each dose modification until reaching the maximum dose.)
- Percentage of participants with platelet transfusion independence(Year 1, Year 2)
- Time to platelet response(Week 24, Year 1, Year 2)
- Percentage of participants with platelet response (Hematologic improvement (HI) - platelet))(Week 24, Year 1, Year 2)
- Quality of Life measured using QLQ-C30(Baseline, every 4 weeks until week 52, every 8 weeks after week 52 up to end of treatment or end of post-treatment follow-up, approximately 3.5 years.)
- PK: Tmax(Intensive: pre-dose, 1, 2, 4, 6, 8, and 24 hours post-dose. Trough: 15th days after starting the initial dose or each dose modification until reaching the maximum dose.)
- PK: AUC(Intensive: pre-dose, 1, 2, 4, 6, 8, and 24 hours post-dose. Trough: 15th days after starting the initial dose or each dose modification until reaching the maximum dose.)
- Overall survival (OS)(Week 24, Year 1, Year 2)
- Pharmacokinetics (PK): Cmax(Intensive: pre-dose, 1, 2, 4, 6, 8, and 24 hours post-dose. Trough: 15th days after starting the initial dose or each dose modification until reaching the maximum dose.)