A Randomized, Double-blind, Placebo-controlled Phase 3 Study of Tamibarotene Plus Azacitidine Versus Placebo Plus Azacitidine in Newly Diagnosed, Adult Patients Selected for RARA-positive Higher-risk Myelodysplastic Syndrome (SELECT MDS-1)
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 246
- 试验地点
- 128
- 主要终点
- Percentage of Participants With Complete Remission (CR)
研究概览
简要总结
This study compares the efficacy of Tamibarotene in combination with azacitidine to azacitidine in combination with placebo in participants who are Retinoic Acid Receptor Alpha (RARA) positive, and newly diagnosed with higher-risk myelodysplastic syndrome (HR-MDS), and who have not received treatment for this diagnosis. The primary goal of the study is to compare the complete remission rate between the two treatment arms.
详细描述
A subset of participants have MDS characterized by an overexpression of the RARA gene. A blood test will be used to identify participants with RARA-positive MDS. Assessment of the RARA biomarker for study eligibility will be done by collection of blood samples from potential study participants at the pre-screening visit and testing at a central laboratory. Participants who meet eligibility requirements will be randomized 2:1 to receive either Tamibarotene plus azacitidine or placebo plus azacitidine.
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)
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
- •Participants must be RARA-positive based on the investigational assay.
- •Participants must be newly diagnosed with HR-MDS as follows:
- •Diagnosis of MDS according to the World Health Organization (WHO) classification and classified by the Revised International Prognostic Scoring System (IPSS R) risk category as very high, high, or intermediate risk.
- •Participants must have Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤
排除标准
- •Participants are suitable for and agree to undergo allogeneic hematopoietic stem cell transplant (HSCT) at the time of screening.
- •Participants who need treatment prior to stem cell transplant can receive treatment on this study and stop the study treatment when they are ready to proceed to transplant.
- •Participants who received prior treatment for MDS with any hypomethylating agent, lenalidomide, chemotherapy or allogeneic HSCT.
研究组 & 干预措施
Tamibarotene + Azacitidine
Tamibarotene: 6 mg administered orally twice per day (BID) on Days 8 through 28 of each 28-day treatment cycle.
Azacitidine: 75 mg/m^2 administered intravenously or subcutaneously each day on Days 1 through 7 of each 28-day treatment cycle.
干预措施: Tamibarotene (Drug)
Tamibarotene + Azacitidine
Tamibarotene: 6 mg administered orally twice per day (BID) on Days 8 through 28 of each 28-day treatment cycle.
Azacitidine: 75 mg/m^2 administered intravenously or subcutaneously each day on Days 1 through 7 of each 28-day treatment cycle.
干预措施: Azacitidine (Drug)
Tamibarotene Matched Placebo + Azacitidine
Placebo: Tamibarotene-matching tablets administered orally BID on Days 8 through 28 of each 28-day treatment cycle.
Azacitidine: 75 mg/m^2 administered intravenously or subcutaneously each day on Days 1 through 7 of each 28-day treatment cycle.
干预措施: Placebo (Drug)
Tamibarotene Matched Placebo + Azacitidine
Placebo: Tamibarotene-matching tablets administered orally BID on Days 8 through 28 of each 28-day treatment cycle.
Azacitidine: 75 mg/m^2 administered intravenously or subcutaneously each day on Days 1 through 7 of each 28-day treatment cycle.
干预措施: Azacitidine (Drug)
结局指标
主要结局
Percentage of Participants With Complete Remission (CR)
时间窗: Up to 45 months
CR was determined by the investigator per the modified International Working Group Myelodysplastic Syndrome (IWG MDS). CR was defined as participants with hemoglobin ≥11 grams/deciliter (g/dL), neutrophils ≥1.0\*10\^9/L, platelets ≥100\*10\^9/L, blasts 0%, bone marrow blasts (BMBs) ≤5% and normal maturation of all cell lines, persistent dysplasia were noted.
次要结局
- Duration of Overall Response (DOR)(Up to 45 months)
- Number of Participants Who Achieved Transfusion Independence (TI)(Up to 45 months)
- Percentage of Participants Who Achieved Overall Response (OR)(Up to 45 months)
- Duration of Complete Response (DOCR)(Up to 45 months)
- Time to Complete Remission (TCR)(Up to 45 months)
- Time to Initial Response (TIR)(Up to 45 months)
- Change in Health-Related Quality of Life (HRQoL) as Assessed by the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 Scale (EORTC QLQ-30)(Up to 45 months)
- Change in HRQOL as Assessed by the European Quality of Life 5 Dimensions Scale (EuroQoL-5D)(Up to 45 months)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(Up to 45 months)