NCT06465953招募中3 期
A Phase 3, Multicenter, Open Label, Randomized, Non-comparative Two-arm Study of Ivosidenib (IVO) Monotherapy and Azacitidine (AZA) Monotherapy in Adult Patients With Hypomethylating Agent (HMA) Naive Myelodysplastic Syndromes (MDS) With an Isocitrate Dehydrogenase-1 (IDH1) Mutation (PyramIDH Study)
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 48
- 试验地点
- 105
- 主要终点
- Number of participants achieving CR and PR by 4 months
研究概览
简要总结
This study will enroll participants with myelodysplastic syndromes (MDS) with an Isocitrate dehydrogenase protein, 1 (IDH1) mutation, who have not received treatment with a hypomethylating agent previously. Participants will be randomized to receive either ivosidenib (IVO) alone or azacitidine (AZA) alone. IVO will be administered daily throughout the 28-day treatment cycle and AZA will be administered for the first 7 days of each 28-day cycle. Study visits will be conducted every week during Cycle 1 (Days 1, 8, 15, and 22), and Day 1 of each cycle thereafter. After the last dose of treatment, participants will attend an safety follow-up visit and participants will be followed to assess overall survival. Study visits may include a bone marrow aspirate, physical exam, echocardiogram (ECHO), electrocardiogram (ECG), blood and urine analysis, and questionnaires.
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
- •Diagnosis of HMA naive IDH1 R132 mutated MDS defined according to WHO criteria (5th edition):
- •Moderate high, high and very high-risk MDS per IPSS-M score will be eligible regardless of blood counts and with blast counts 0-19%.
- •Low and moderate low-risk MDS per IPSS-M score must:
- •Have cytopenias related to MDS, defined as: <100 platelets/microliter, or absolute neutrophil count (ANC) <1000/mm3, or hemoglobin <10g/dL AND
- •Have a blast count between 5-19% AND
- •Be eligible for HMA therapy (very low risk participants are to be excluded)
- •Locally or centrally confirmed IDH1 R132 C/G/H/L/S mutation
排除标准
- •Received prior anticancer/disease modifying treatment for MDS (including HMA's, cytotoxic chemotherapy, investigational agents, bcl-2 inhibitor based-regimens, hematopoietic stem cell transplant (HSCT), IDH1 inhibitors). For LR-MDS patients, prior treatment with growth factors, luspatercept, lenalidomide, and imetelstat are allowed.
- •>20% blasts by morphology or immunohistochemistry on screening bone marrow aspirate/biopsy
研究组 & 干预措施
Ivosidenib monotherapy
Experimental
干预措施: Ivosidenib (Drug)
Azacitidine monotherapy
Experimental
干预措施: Azacitidine (Drug)
结局指标
主要结局
Number of participants achieving CR and PR by 4 months
时间窗: Through 4 months after starting treatment
Complete remission (CR) or Partial remission (PR) as per International Working Group (IWG) 2006 criteria
次要结局
- Overall Response (OR) rate per IWG 2023 criteria(Through the end of the study (approximately 4 years))
- Event-free survival (EFS)(Through the end of the study (approximately 4 years))
- Overall Survival (OS)(Through the end of the study (approximately 4 years))
- Duration of CR and PR(Through the end of the study (approximately 4 years))
- Time to CR and PR(Through the end of the study (approximately 4 years))
- Acute myeloid leukemia (AML) transformation rate(Through the end of the study (approximately 4 years))
- Time to transfusion independence (TTTI)(Through the end of the study (approximately 4 years))
- Duration of transfusion independence (DOTI)(Through the end of the study (approximately 4 years))
- Transfusion independence rate(Through the end of the study (approximately 4 years))
- Change from baseline in Quality of life (QOL) based on the QUALMS score(Through the Event Free Survival Follow up (approximately 4 years))
- Change from baseline in health economic outcomes measures based on EQ-5D-5L score(Through the Event Free Survival Follow up (approximately 4 years))
- Number of participants who proceed to hematopoietic stem cell transplantation (HSCT)(Through the end of the study (approximately 4 years))
- Ivosidenib plasma concentrations(Through Cycle 22 (each cycle is 28 days))
- 2-HG plasma concentrations(Through Cycle 22 (each cycle is 28 days))
- Number of adverse events (AEs) and serious adverse events (SAEs)(Through the Safety Follow-up Visit (30-35 days after discontinuation of treatment))
- Overall Response (OR) rate per IWG 2023 criteria(Through the end of the study (approximately 4 years))
- Event-free survival (EFS)(Through the end of the study (approximately 4 years))
- Overall Survival (OS)(Through the end of the study (approximately 4 years))
- Duration of CR and PR(Through the end of the study (approximately 4 years))
- Time to CR and PR(Through the end of the study (approximately 4 years))
- Acute myeloid leukemia (AML) transformation rate(Through the end of the study (approximately 4 years))
- Time to transfusion independence (TTTI)(Through the end of the study (approximately 4 years))
- Duration of transfusion independence (DOTI)(Through the end of the study (approximately 4 years))
- Transfusion independence rate(Through the end of the study (approximately 4 years))
- Change from baseline in Quality of life (QOL) based on the QUALMS score(Through the Event Free Survival Follow up (approximately 4 years))
- Change from baseline in health economic outcomes measures based on EQ-5D-5L score(Through the Event Free Survival Follow up (approximately 4 years))
- Number of participants who proceed to hematopoietic stem cell transplantation (HSCT)(Through the end of the study (approximately 4 years))
- Ivosidenib plasma concentrations(Through Cycle 22 (each cycle is 28 days))
- 2-HG plasma concentrations(Through Cycle 22 (each cycle is 28 days))
- Number of participants achieving CR and PR by 6 months as per IWG 2006 criteria(Through 6 months after starting treatment)
- Number of participants achieving CR and PR by 6 months as per IWG 2023 criteria(Through 6 months after starting treatment)
- Number of participants achieving CR and PR by 4 months as per IWG 2023 criteria(Through 4 months after starting treatment)
- Number of adverse events (AEs) and serious adverse events (SAEs)(Through the Safety Follow-up Visit (30-35 days after discontinuation of treatment))
研究者
研究点 (105)
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