Phase 2/3 Study of Monotherapy LY2157299 Monohydrate in Very Low-, Low-, and Intermediate-Risk Patients With Myelodysplastic Syndromes
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 43
- 试验地点
- 1
- 主要终点
- Percentage of Participants With Hematological Improvement (HI)
研究概览
简要总结
The purpose of this study is to investigate the effect of the study drug known as galunisertib in participants with myelodysplastic syndromes (MDS). Participants with different degrees of disease (very low, low, and intermediate risk) will be studied. The study treatment is expected to last about 6 months for each participant.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Confirmed diagnosis of MDS based on the World Health Organization (WHO) criteria
- •Participants with 5q deletions are allowed only if they have failed or are intolerant of lenalidomide treatment
- •Participants must have a Revised International Prognostic Scoring System (IPSS-R) category of very low-, low-, or intermediate-risk disease
- •In the 8 weeks prior to registration, participants in phase 2 should have anemia with Hb ≤10.0 g/dL (based on the average of 2 baseline measurements and untransfused for at least 1 week) with or without red blood cell (RBC) transfusion dependence confirmed for a minimum of 8 weeks before enrollment
- •For phase 3, participants should have anemia with RBC transfusion dependence confirmed within 8 weeks before enrollment
- •Performance status ≤2 on the Eastern Cooperative Oncology Group (ECOG) scale
排除标准
- •No history of moderate or severe cardiac disease
- •No prior history of acute myeloid leukemia (AML)
研究组 & 干预措施
Phase (ph) 2: Galunisertib + BSC
Ph 2. 150 milligrams Galunisertib given orally twice daily (BID) for 14 days followed by 14 days with no study drug (28 day cycles). Participants will receive best supportive care (BSC) according to institutional guidelines. Treatment is expected to last for 6 cycles. Participants may receive additional cycles if they are deriving clinical benefit.
干预措施: Galunisertib (Drug)
Ph 3: Placebo + BSC
Placebo administered orally BID for 14 days followed by 14 days with no study drug (28 day cycles). Participants will receive BSC according to institutional guidelines. Treatment is expected to last for 6 cycles. Participants may receive additional cycles if they are deriving clinical benefit. This arm is contingent on the data from the phase 2 arm.
干预措施: Placebo (Drug)
Ph 3: Galunisertib + BSC
150 milligrams Galunisertib given orally twice daily (BID) for 14 days followed by 14 days with no study drug (28 day cycles). Participants will receive best supportive care (BSC) according to institutional guidelines. Treatment is expected to last for 6 cycles. Participants may receive additional cycles if they are deriving clinical benefit. This arm is contingent on the data from the phase 2 arm.
干预措施: Galunisertib (Drug)
结局指标
主要结局
Percentage of Participants With Hematological Improvement (HI)
时间窗: Baseline through end of study treatment (24 weeks)
Percentage of participants with hematological improvement (HI) based on International Working Group (IWG) 2006 criteria in participants with very low, low, and intermediate-risk myelodysplastic syndromes treated with Galunisertib plus best supportive care, as assessed by the International Prognostic Scoring System (IPSS-R). To be classified as an HI responder, the HI response must have lasted at least 8 weeks (56 days).
Percentage of Participants Who Are Transfusion-free or Have Hemoglobin (Hb) Increase ≥1.5 Grams/Deciliter Maintained for 8 Weeks During Phase 3
时间窗: Baseline through end of study treatment (24 weeks)
Comparison of the percentage of participants with very low-, low-,and intermediate-risk MDS who were transfusion-free or had an increase ≥1.5 g/dL in hemoglobin (Hb) maintained for at least 8 weeks within the first 24 weeks of treatment with galunisertib plus best supportive care or placebo plus best supportive care and assessed by IPSS-R. The Phase 3 portion of this study was not conducted because efficacy level required in phase 2 to move forward to phase 3 was not achieved.
次要结局
- Change From Baseline in EuroQol 5-Dimension 5 Level Instrument(Phase 3: Baseline, Cycle 2, Cycle 4, Cycle 6 (Cycle = 28 days))
- Overall Survival (OS)(Baseline to date of death from any cause (Up to 2 years))
- Change From Baseline in Brief Fatigue Inventory (BFI)(Baseline, Follow up (final visit up to 24 months))
- Percentage of Participants With Cytogenetic Response(Baseline through end of study treatment (24 weeks))
- Percentage of Participants Who Are Hospitalized (Resource Utilization)(Baseline through end of study treatment (24 weeks))
- Population Pharmacokinetics (PK): Mean Population Clearance of Galunisertib(Day 1 pre-dose & between 0.5 to 2 hours post dose; Day 14 pre-dose, between 0.5 to 2 & between 3 to 5 hours post dose; Days 15 & 16 (if logistically possible) between 0.5 to 2 hours post dose)
- Number of Participants With a Change in Bone Marrow Fibrosis Grading(Baseline, Cycle 6 (Cycle = 28 days))