A Single Arm, Open-label Phase 3b Study to Describe the Safety and Tolerability of Ivosidenib in Combination With Azacitidine in Adult Patients Newly Diagnosed With IDH1m Acute Myeloid Leukemia (AML) Ineligible for Intensive Induction Chemotherapy
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 245
- 试验地点
- 15
- 主要终点
- Number of Adverse Events (AEs)
研究概览
简要总结
The purpose of this study is to learn more about the safety and efficacy of ivosidenib taken with azacitidine to treat adult patients with acute myeloid leukemia (AML) who are presenting a gene mutation called IDH1 (isocitrate dehydrogenase1 mutation-positive [IDH1m]) and cannot receive treatment with intensive chemotherapy (IC).
详细描述
Participants who are eligible and enroll in the study will attend a study visit on the first day of each 28-day cycle. Study visits will consist of a physical exam, blood work, electrocardiogram (ECG) and other assessments. After treatment discontinuation participants will be contacted every 12 weeks through the end of the study (currently planned for 2026) to assess survival. The study drug, Ivosidenib, will be taken once daily throughout the duration of participation in the study, and Azacitidine will only be administered for 7 days at the beginning of each 28 day cycle. If at any point ivosidenib is made available as a medical prescription at the patient's site, the patient will switch to commercial product and will continue to be followed according to the protocol.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Has untreated Acute Myeloid Leukemia (AML)
- •Have a documented IDH1 R132 gene-mutated disease
- •Have at least one of the following making yourself ineligible for intensive chemotherapy (IC): 75 years or older, Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 2, or any comorbidity that the investigator judges to be incompatible with IC including but not limited to severe cardiac or pulmonary disorder, creatinine clearance less than 45 mL/minute, or bilirubin greater than 1.5 times the upper limit of normal
- •Has adequate hepatic (liver) and renal (kidney) function
- •Female participants of reproductive potential must have a negative blood pregnancy test and must use effective contraception during treatment and for at least 6 months following treatment
- •Fertile male participants with female partners of reproductive potential must use effective contraception during treatment and for at least 3 months following treatment
排除标准
- •Has received any prior treatment for AML, with the exception of hydroxyurea or leukapheresis for white blood cell count control
- •Has received prior treatment with an IDH1 inhibitor
- •Is a woman who is pregnant or breastfeeding
- •Has an active, uncontrolled, systemic fungal, bacterial, or viral infection (including human immunodeficiency virus [HIV], active hepatitis B (HBV), or hepatitis C virus [HCV]) without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment
- •Has had significant active cardiac disease within 6 months prior to the start of study treatment, including Class III or IV congestive heart failure, myocardial infarction (heart attack), unstable angina (chest pain), and/or stroke
- •Has dysphagia (difficulty swallowing), short-gut syndrome, gastroparesis (stomach paralysis), or any other condition that limits the ingestion or gastrointestinal absorption of orally administered drugs
- •Has uncontrolled hypertension (high blood pressure)
研究组 & 干预措施
Open-Label Ivosidenib in combination with Azacitidine
All participants will receive both Ivosidenib and Azacitidine for a maximum of 28 cycles. Each cycle will be 4 weeks or 28 days long. Ivosidenib will be taken continuously throughout each cycle and Azacitidine will be taken only for 7 days at the beginning of each cycle.
干预措施: Ivosidenib 500mg Oral Tablet (Drug)
Open-Label Ivosidenib in combination with Azacitidine
All participants will receive both Ivosidenib and Azacitidine for a maximum of 28 cycles. Each cycle will be 4 weeks or 28 days long. Ivosidenib will be taken continuously throughout each cycle and Azacitidine will be taken only for 7 days at the beginning of each cycle.
干预措施: Azacitidine (Drug)
结局指标
主要结局
Number of Adverse Events (AEs)
时间窗: up to week 116
Adverse events (AEs) will be graded according to the CTCAE v5.0
Differentiation Syndrome of Grade 2 or higher
时间窗: up to week 116
Rate of infections
时间窗: up to week 116
Infection rates will be summarized by classification and will include a count and proportion.
QT Prolongation event assessed as Grade 3 or higher
时间窗: up to week 116
Number of Adverse Events (AEs) leading to ivosidenib + azacitidine discontinuation
时间窗: up to week 112
Number of Adverse Events (AEs) leading to ivosidenib + azacitidine dose reduction
时间窗: up to week 112
Number of Adverse Events (AEs) leading to death
时间窗: up to week 116
Number of clinical laboratory anomalies assessed as Adverse Events (AEs)
时间窗: up to week 116
Number of patients requiring transfusion (platelet and RBC) and the average number of units transfused
时间窗: up to week 116
Number of Serious Adverse Events (SAEs)
时间窗: up to week 116
Adverse events (AEs) will be graded according to the CTCAE v5.0
Number of Adverse Events (AEs) leading to ivosidenib + azacitidine interruption
时间窗: up to week 112
次要结局
- Proportion of patients who achieve complete remission plus complete remission with partial hematologic recovery rate (CR + CRh)(up to week 116)
- Duration of response (DOR)(up to week 116)
- Health economic measures, as assessed by the 5-level EuroQol 5-Dimensions (EQ-5D-5L)(up to week 116)
- Overall survival (OS)(until study closure)
- Average proportion of days at home(up to week 116)
- Proportion of patients who achieve a complete remission (CR)(up to week 116)
- Event-free survival (EFS)(up to week 116)
- Quality of life (QoL), as measured by Hematologic Malignancy-Patient-Reported Outcome (HM-PRO)(up to week 116)
- Quality of life (QoL), as measured by Family Reported Outcome Measure (FROM-16), for caregivers and/or family(up to week 116)
- Proportion of patients who achieve complete remission plus complete remission with incomplete hematologic recovery rate (CR + CRi)(up to week 116)
- Time to response (TTR)(up to week 116)