NCT03682536进行中（未招募）3 期
A Phase 3, Open-label, Randomized Study to Compare the Efficacy and Safety of Luspatercept (ACE-536) Versus Epoetin Alpha for the Treatment of Anemia Due to IPSS-R Very Low, Low or Intermediate Risk Due to Myelodysplastic Syndrome (MDS) in ESA Naïve Subjects Who Require Red Blood Cell Transfusions
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- Celgene
- 入组人数
- 363
- 试验地点
- 226
- 主要终点
- Percentage of Participants With Red Blood Cell Transfusion Independence (RBC-TI) for 12 Weeks (84 Days) With a Mean Hemoglobin Increase ≥ 1.5 g/dL
研究概览
简要总结
The purpose of this study is to determine the effectiveness of luspatercept (ACE-536) compared to epoetin alfa on red blood cell (RBC) transfusion independence (for at least 12 weeks) with a concurrent hemoglobin increase of at least 1.5 g/dL in participants with anemia due to revised international prognostic scoring system (IPSS-R) very low, low, or intermediate risk myelodysplastic syndromes (MDS) who require RBC transfusions and have never been exposed to erythropoiesis stimulating agent (ESA).
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
- •Documented diagnosis of Myelodysplastic syndromes (MDS) according to WHO 2016 classification that meets revised international prognostic scoring system (IPSS-R) classification of very low, low, or intermediate risk disease, and have < 5% blasts in bone marrow
- •Endogenous serum erythropoietin (sEPO) level of < 500 U/L
- •Requires Red blood cell (RBC) transfusions, as documented by the criteria: Average transfusion requirement of 2 - 6 units/8 weeks of packed red blood cells (pRBCs) confirmed for a minimum of 8 weeks immediately preceding randomization
- •Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2
排除标准
- •Clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or hypothyroidism, or any type of known clinically significant bleeding or sequestration or drug induced anemia
- •Known history of diagnosis of Acute myeloid leukemia (AML)
- •Uncontrolled hypertension, defined as repeated elevations of systolic blood pressure (SBP) of ≥ 150 mmHg and/or diastolic blood pressure (DBP) ≥ 100 mmHg despite adequate treatment
- •Other protocol-defined inclusion/exclusion criteria apply
研究组 & 干预措施
Luspatercept
Experimental
干预措施: Luspatercept (Drug)
Epoetin alfa
Active Comparator
干预措施: Epoetin alfa (Drug)
结局指标
主要结局
Percentage of Participants With Red Blood Cell Transfusion Independence (RBC-TI) for 12 Weeks (84 Days) With a Mean Hemoglobin Increase ≥ 1.5 g/dL
时间窗: Week 1 through Week 24
Percentage of participants who are RBC transfusion-free for any 12-week period associated with a concurrent mean hemoglobin (Hgb) increase ≥ 1.5 g/dL compared to baseline. After applying below 14/3-day rule, the baseline Hgb value is defined as the lowest Hgb value from the central, local laboratory, or pre transfusion Hgb from transfusion records that is within 56 days on or prior to the first dose of treatment, or randomization date if participants were not treated. 4/3-day rule: only Hgb values that are at least 14 days after a transfusion may be used unless there is another transfusion within 3 days after the Hgb assessment. If this occurs, that Hgb value will be used despite being \< 14 days after the previous transfusion.
次要结局
- Percentage of Participants With Red Blood Cell Transfusion Independence (RBC-TI) for 24 Weeks(Week 1 through Week 24)
- Mean Hemoglobin Change Over 24 Weeks(Week 1 through Week 24)
- Percentage of Participants Achieving Red Blood Cell Transfusion Independence (RBC-TI) for ≥ 12 Weeks (84 Days)(Week 1 through Week 24)
- Percentage of Participants Achieving Hematologic Improvement - Erythroid Response (HI-E) Per IWG(Week 1 through Week 24)
- The Number of Participants With Adverse Events (AEs)(From first dose to 42 days post last dose (Up to approximately an average of 72 weeks and a maximum of 208 weeks))
- Number of Participants With a Positive Anti-drug Antibody (ADA) Test(Day 1 on week 4, 10, 16, 22, and every 12 weeks (±14 days) from the 24-Week MDS Assessment visit for up to one year from the first dose)
- Area Under the Concentration-time Curve [AUC](Day 1 on week 4, 10, 16, 22, and every 12 weeks (±14 days) from the 24-Week MDS Assessment visit for up to one year from the first dose)
- Time to Hematologic Improvement - Erythroid Response (HI-E)(Week 1 through Week 24)
- Time to First Red Blood Cell (RBC) Transfusion(Week 1 through End of Treatment (Up to approximately an average of 66 weeks and a maximum of 202 weeks))
- Percentage of Participants Achieving Red Blood Cell Transfusion Independence (RBC-TI) for ≥ 56 Days (8 Weeks)(Week 1 through Week 24)
- Percentage of Participants Achieving Red Blood Cell Transfusion Independence (RBC-TI) for a Consecutive 24-week Period(Week 1 through Week 48)
- Change From Baseline in the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30)(Baseline and week 24.)
- Duration of Red Blood Cell Transfusion Independence (RBC-TI) ≥ 12 Weeks (84 Days)(Week 1 through End of Treatment (Up to approximately an average of 66 weeks and a maximum of 202 weeks))
- Time to Red Blood Cell Transfusion Independence (RBC-TI) ≥ 12 Weeks (84 Days)(Week 1 through Week 24)
- The Number of Red Blood Cell (RBC) Units Transfused Within the First 24 Weeks of Treatment(Week 1 through Week 24)
- The Number of Participants With Acute Myeloid Leukemia (AML) Progression(From randomization to 5 years from first dose or 3 years from last dose (whichever occurs later), unless the participant withdraws consent from the study, dies or is lost to follow-up. (Up to approximately 221 weeks))
- Median Time to Acute Myeloid Leukemia (AML) Progression(From randomization to first diagnosis of AML up to 5 years from first dose or 3 years from last dose (whichever occurs later), unless the participant withdraws consent from the study, dies or is lost to follow-up. (Up to approximately 221 weeks))
- Overall Survival (OS)(Randomization to death due to any cause up to 5 years from first dose or 3 years from last dose (whichever occurs later), unless the participant withdraws consent from the study, dies or is lost to follow-up. (Up to approximately 221 weeks))
- Maximum Plasma Concentration of Drug [Cmax](Day 1 on week 4, 10, 16, 22, and every 12 weeks (±14 days) from the 24-Week MDS Assessment visit for up to one year from the first dose)
- Change From Baseline in the Functional Assessment of Cancer Therapy-Anemia Version 4 (FACT-An)(Baseline, Day 1 on weeks 7,13,19, and 24.)
研究者
研究点 (226)
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相关资讯
Luspatercept Demonstrates Durable Transfusion Independence in Lower-Risk MDS Across Two Pivotal Trials- In the phase 3b MAXILUS trial, 81.5% of ESA-naive patients with lower-risk MDS achieved RBC transfusion independence for ≥8 weeks plus concurrent Hb increase ≥1 g/dL.
- Long-term COMMANDS data show luspatercept nearly doubled the duration of transfusion independence compared with epoetin alfa, with some "super-responders" remaining transfusion-free for ≥2.5 years.
- MAXILUS results affirm the importance of early treatment initiation with luspatercept at the maximum approved dose in both ESA-naive and ESA-relapsed/refractory populations.
- Both trials reinforce luspatercept's role as a frontline standard in lower-risk MDS, raising expectations for durable transfusion independence.3 months agoLuspatercept Shows Survival Advantage Over ESA in Low-Risk MDS After Three Years- Luspatercept doubled transfusion independence rates compared to erythropoietin-stimulating agents in the phase 3 COMMANDS trial, achieving 60% versus 35% response rates in low-risk myelodysplastic syndromes.
- The survival benefit emerged after three years of treatment, with luspatercept showing superior overall survival compared to ESA in a piecewise analysis at 36 months or longer.
- Duration of transfusion independence was significantly longer with luspatercept, particularly benefiting patients with SF3B1 mutations who achieved 70% response rates versus 33% with ESA.
- The survival advantage appears linked to sustained transfusion independence rather than disease modification, potentially reducing cardiovascular mortality in this elderly patient population.9 months agoReblozyl Shows Promise as First-Line Treatment for Myelodysplastic Syndromes in Phase 3 Trial- Bristol Myers Squibb's Reblozyl demonstrated statistically significant and clinically meaningful improvements in red blood cell transfusion independence in a Phase 3 trial for myelodysplastic syndromes.
- The COMMANDS study evaluated Reblozyl versus epoetin alfa in transfusion-dependent, erythropoiesis stimulating agent-naïve patients with very low-, low-, and intermediate-risk myelodysplastic syndromes.
- Reblozyl met the primary endpoint of red blood cell transfusion independence for 12 weeks and key secondary endpoints, including transfusion independence at 24 weeks.
- These results suggest Reblozyl could address a significant unmet need for improved first-line treatment options in patients with transfusion-dependent myelodysplastic syndromes.last yearLuspatercept and Novel Therapies Reshape Treatment Strategies in Myelodysplastic Syndromes- The COMMANDS trial demonstrated that luspatercept significantly improved red blood cell transfusion independence compared to epoetin alfa in patients with low-risk MDS.
- Imetelstat has shown promise in patients with prior ESA treatment, exhibiting a 34% transfusion independence rate, potentially modifying the disease course by reducing mutation burden.
- Lenalidomide has been confirmed to prolong time to transfusion dependence in low-risk MDS patients with del(5q), while ivosidenib offers a treatment option for relapsed or refractory MDS with _IDH1_ mutation.
- Molecular assessment is increasingly crucial in defining MDS, leading to more specific diagnostic criteria and therapeutic strategies, including targeting rare mutations like _IDH1_.last yearLuspatercept Improves Quality of Life in First-Line Treatment of Anemia in Lower-Risk MDS- Luspatercept's approval offers an effective and well-tolerated first-line treatment for anemia in lower-risk myelodysplastic syndrome (MDS) patients without prior ESA use.
- The COMMANDS trial demonstrated luspatercept's significant advantage over ESAs in treating anemia, leading to improved fatigue and overall quality of life (QOL) for patients.
- Treatment goals for lower-risk MDS focus on enhancing QOL and managing anemia symptoms, as curative options like stem cell transplants are often unsuitable for this patient group.
- Ongoing research aims to discover transformative approaches that can change the disease's natural history and provide a potential cure for MDS, addressing the limitations of current treatments.last year
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