A Phase II Multicenter Open-label Trial of Tagraxofusp (Tag) in Combination With Venetoclax and Azacitidine (Ven/Aza) in Adults With Previously Untreated CD123+ Acute Myeloid Leukemia (AML) Who Are Ineligible for Intensive Chemotherapy
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 85
- 试验地点
- 67
- 主要终点
- Part 1: Determination of Part 2 Selected Dose of Tagraxofusp When Administered in Combination with Venetoclax and Azacitidine
研究概览
简要总结
This study will be divided into 2 parts (Part 1 and Part 2). Part 1 will evaluate 2 doses of tagraxofusp (9 and 12 micrograms/kilogram/day [μg/kg/day]), used in combination with venetoclax and azacitidine, to determine the dose for Part 2. This determined dose, in combination with venetoclax and azacitidine, will then be further evaluated in Part 2 in 2 cohorts (TP53 mutated and TP53 wild type). Both parts will be conducted in participants with previously untreated CD123+ AML who are ineligible for intensive chemotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 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
- •Previously untreated with histological confirmation of AML by World Health Organization 2022 criteria and are ineligible for treatment with a standard cytarabine and anthracycline induction regimen due to age, or comorbidity.
- •Participant has any level of CD123 expression on blasts.
- •Participants must be considered ineligible for intensive chemotherapy, defined by the following:
- •≥75 years of age; or
- •≥18 to 74 years of age with at least 1 of the following:
- •Eastern Cooperative Oncology Group (ECOG) performance status of 2 or
- •Diffusing capacity of the lung for carbon monoxide of ≤65% or forced expiratory volume in 1 second ≤65%.
- •Baseline creatinine clearance ≥30 to <45 milliliters/minute calculated by the Cockcroft Gault formula or measured by 24-hour urine collection.
- •Hepatic disorder with total bilirubin >1.5 x upper limit of normal.
- •Any other condition for which the physician judges the participant to be unsuitable for intensive chemotherapy.
- •ECOG performance status:
- •0 to 2 for participants ≥75 years of age, or
- •0 to 3 for participants ≥18 to 74 years of age.
排除标准
- •Participant has received prior therapy for AML.
- •Participant is willing and able to receive standard induction therapy.
- •Participant has received treatment for an antecedent hematologic disease with a hypomethylating agent, venetoclax, tagraxofusp, purine analogue, cytarabine, intensive chemotherapy, SCT, chimeric antigen receptor-T therapy, or other experimental therapies.
- •Participant has AML with central nervous system involvement.
- •Note: Other inclusion/exclusion criteria may apply.
研究组 & 干预措施
Part 1 - Tagraxofusp (9 μg/kg/day)
Participants will receive tagraxofusp in combination with venetoclax and azacitidine.
干预措施: Tagraxofusp (Drug)
Part 1 - Tagraxofusp (12 μg/kg/day)
Participants will receive tagraxofusp in combination with venetoclax and azacitidine.
干预措施: Tagraxofusp (Drug)
Part 1 - Tagraxofusp (9 μg/kg/day)
Participants will receive tagraxofusp in combination with venetoclax and azacitidine.
干预措施: Venetoclax (Drug)
Part 1 - Tagraxofusp (12 μg/kg/day)
Participants will receive tagraxofusp in combination with venetoclax and azacitidine.
干预措施: Venetoclax (Drug)
Part 1 - Tagraxofusp (12 μg/kg/day)
Participants will receive tagraxofusp in combination with venetoclax and azacitidine.
干预措施: Azacitidine (Drug)
Part 2 - Tagraxofusp (Selected Dose) and TP53 Wild Type
Participants (TP53 wild type) will receive tagraxofusp in combination with venetoclax and azacitidine.
干预措施: Tagraxofusp (Drug)
Part 2 - Tagraxofusp (Selected Dose) and TP53 Wild Type
Participants (TP53 wild type) will receive tagraxofusp in combination with venetoclax and azacitidine.
干预措施: Venetoclax (Drug)
Part 2 - Tagraxofusp (Selected Dose) and TP53 Wild Type
Participants (TP53 wild type) will receive tagraxofusp in combination with venetoclax and azacitidine.
干预措施: Azacitidine (Drug)
Part 2 - Tagraxofusp (Selected Dose) and TP53 Mutated
Participants (TP53 mutated) will receive tagraxofusp in combination with venetoclax and azacitidine.
干预措施: Azacitidine (Drug)
Part 1 - Tagraxofusp (9 μg/kg/day)
Participants will receive tagraxofusp in combination with venetoclax and azacitidine.
干预措施: Azacitidine (Drug)
Part 2 - Tagraxofusp (Selected Dose) and TP53 Mutated
Participants (TP53 mutated) will receive tagraxofusp in combination with venetoclax and azacitidine.
干预措施: Venetoclax (Drug)
Part 2 - Tagraxofusp (Selected Dose) and TP53 Mutated
Participants (TP53 mutated) will receive tagraxofusp in combination with venetoclax and azacitidine.
干预措施: Tagraxofusp (Drug)
结局指标
主要结局
Part 1: Determination of Part 2 Selected Dose of Tagraxofusp When Administered in Combination with Venetoclax and Azacitidine
时间窗: Cycles 1-4 (up to 112 days; 28 days/cycle)
Part 2: Number of Participants Achieving a Best Overall Response (BOR) of Complete Remission (CR)
时间窗: Cycles 1-4 (up to 112 days; 28 days/cycle)
次要结局
- Parts 1 and 2: Time to First CR(Cycles 1-6 (up to 168 days; 28 days/cycle))
- Parts 1 and 2: Duration of Response(Cycles 1-6 (up to 168 days; 28 days/cycle))
- Parts 1 and 2: Number of Participants Achieving a BOR of CR, CR with Incomplete Hematologic Recovery (CRi), or CR with Partial Hematologic Recovery (CRh)(Cycles 1-4 (up to 112 days; 28 days/cycle))
- Parts 1 and 2: Number of Participants Who Bridged to Stem Cell Transplant (SCT) Through Study Treatment(Up to approximately 6 years)
- Part 1: Plasma Concentration of Free Tagraxofusp, Venetoclax, and Azacitidine(Predose, up to 8 hours post dose (Days 4, 5, 6, 7, 14; Cycles 1-4; 28 days/cycle))
- Parts 1 and 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(Up to approximately 6 years)
- Parts 1 and 2: Overall Survival(Up to approximately 6 years)
- Parts 1 and 2: Maximum Plasma Concentration (Cmax) of Tagraxofusp and Venetoclax(Predose, up to 8 hours post dose (Days 4, 5, 6, 7, 14; Cycles 1-4; 28 days/cycle))
- Parts 1 and 2: Time to Reach Cmax (Tmax) of Tagraxofusp and Venetoclax(Predose, up to 8 hours post dose (Days 4, 5, 6, 7, 14; Cycles 1-4; 28 days/cycle))
- Parts 1 and 2: Area Under the Concentration-time Curve (AUC) of Tagraxofusp and Venetoclax(Predose, up to 8 hours post dose (Days 4, 5, 6, 7, 14; Cycles 1-4; 28 days/cycle))
- Parts 1 and 2: Number of Participants Achieving a BOR of CR(Cycles 1-6 (up to 168 days; 28 days/cycle))
- Parts 1 and 2: Time to First CR(Cycles 1-6 (up to 168 days; 28 days/cycle))
- Parts 1 and 2: Duration of Response(Cycles 1-6 (up to 168 days; 28 days/cycle))
- Parts 1 and 2: Number of Participants Achieving a BOR of CR, CR with Incomplete Hematologic Recovery (CRi), or CR with Partial Hematologic Recovery (CRh)(Cycles 1-4 (up to 112 days; 28 days/cycle))
- Parts 1 and 2: Time to First Composite CR(Cycles 1-4 (up to 112 days; 28 days/cycle))
- Parts 1 and 2: Number of Participants Achieving a BOR of CR or CRi(Cycles 1-6 (up to 168 days; 28 days/cycle))
- Parts 1 and 2: Time to first CR/CRi(Cycles 1-6 (up to 168 days; 28 days/cycle))
- Parts 1 and 2: Event-free Survival (EFS)(Up to approximately 6 years)
- Parts 1 and 2: CR with Minimal Residual Disease (MRD) Negative(Cycles 1-6 (up to 168 days; 28 days/cycle))
- Parts 1 and 2: Number of Participants Who Bridged to Stem Cell Transplant (SCT) Through Study Treatment(Up to approximately 6 years)
- Part 1: Plasma Concentration of Free Tagraxofusp, Venetoclax, and Azacitidine(Predose, up to 8 hours post dose (Days 4, 5, 6, 7, 14; Cycles 1-4; 28 days/cycle))
- Part 2: Plasma Concentration of Free Tagraxofusp and Venetoclax(Predose, up to 8 hours post dose (Days 4, 5, 6, 7, 14; Cycles 1-4; 28 days/cycle))
- Parts 1 and 2: Number of Participants With Serum Anti-drug Antibodies for Tagraxofusp, Venetoclax, and Azacitidine(Day 4 of each cycle (each cycle is 28 days) up to the end of study (approximately 6 years))
- Parts 1 and 2: Exposure-response of Free Tagraxofusp When Administered in Combination with Venetoclax and Azacitidine(Up to approximately 6 years)
- Parts 1 and 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(Up to approximately 6 years)
- Parts 1 and 2: Overall Survival(Up to approximately 6 years)
- Parts 1 and 2: Maximum Plasma Concentration (Cmax) of Tagraxofusp and Venetoclax(Predose, up to 8 hours post dose (Days 4, 5, 6, 7, 14; Cycles 1-4; 28 days/cycle))
- Parts 1 and 2: Time to Reach Cmax (Tmax) of Tagraxofusp and Venetoclax(Predose, up to 8 hours post dose (Days 4, 5, 6, 7, 14; Cycles 1-4; 28 days/cycle))
- Parts 1 and 2: Area Under the Concentration-time Curve (AUC) of Tagraxofusp and Venetoclax(Predose, up to 8 hours post dose (Days 4, 5, 6, 7, 14; Cycles 1-4; 28 days/cycle))