A Randomized, Open Label Phase 3 Study Evaluating Safety and Efficacy of Venetoclax in Combination With Azacitidine After Allogeneic Stem Cell Transplantation in Subjects With Acute Myeloid Leukemia (AML) (VIALE-T)
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 465
- 试验地点
- 330
- 主要终点
- Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Venetoclax and Azacitidine (Part 1)
研究概览
简要总结
The main objective of this study is to evaluate the efficacy of venetoclax in combination with azacitidine to improve Overall Survival (OS) in Acute Myeloid Leukemia (AML) participants compared to Best Supportive Care (BSC) when given as maintenance therapy following allogeneic stem cell transplantation (SCT).
This study will have 2 parts: Part 1 (Dose Confirmation), which may include participants who are greater than or equal to 18 years old; Part 2 (Randomization) which may include participants who are greater than or equal to 12 years old. During Part 1, recommended Phase 3 dose of venetoclax in combination with azacitidine will be determined and during Part 2, the efficacy and safety of venetoclax with azacitidine (Part 2 Arm A) will be compared with BSC (Part 2 Arm B).
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
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must be at least 18 years old for Part 1 and, at least 12 years old for Part
- •Participant must be diagnosed with Acute Myeloid Leukemia (AML) by World Health Organization (WHO) criteria (2017) and either be planning for allogeneic stem cell transplantation or have received allogeneic stem cell transplantation within the past 60 days.
- •Blast percentage in bone marrow before transplant must be < 10%.
- •Blast count in peripheral blood must be "0" and Blast percentage in bone marrow must be < 5% after transplant.
- •Participant meet adequate renal, hepatic and hematologic criteria as described in the protocol.
- •Participants >= 17 years old must have a Karnofsky Performance Scale (KPS) score > 50 and participants between 12 to 16 years old must have a Lansky Play Performance Scale score > 40.
排除标准
- •History of disease progression during prior treatment with venetoclax.
- •History of any other malignancy within 2 years prior to study entry, except for: Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast; basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; previous malignancy confined and surgically resected (or treated with other modalities) with curative intent; Myelodysplastic Syndrome, Myeloproliferative neoplasm (only allowed if it transformed to AML and AML should be the indication for marrow transplantation).
- •Participant has known infection with HIV or history of being positive for hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
- •Presence of clinical or laboratory symptoms/signs of extramedullary myeloid malignancy.
研究组 & 干预措施
Part 1: Venetoclax + Azacitidine (AZA) + Best Supportive Care
Participants will be administered various doses and dose regiments of venetoclax and AZA. Venetoclax will be administered once daily (QD) (Days 1-28) for up to 24 cycles, AZA QD on Days 1-5 of each 28-day cycle for up to 6 cycles and best supportive care (BSC) for 24 cycles (each cycle = 28 days)
干预措施: Best Supportive Care (BSC) (Other)
Part 2: Arm A - Venetoclax + Azacitidine (AZA) + BSC
Participants will be administered with venetoclax and AZA at a dose level determined in Part 1 in addition to best supportive care (when required). Venetoclax will be administered once daily (QD) (Days 1-28) for up to 24 cycles, AZA QD on Days 1-5 of each 28-day cycle for up to 6 cycles and best supportive care (BSC) for 24 cycles (each cycle = 28 days).
干预措施: Best Supportive Care (BSC) (Other)
Part 2: Arm B - Best Supportive Care (BSC)
Participants will receive treatment as prescribed by their physician according to the BSC for up to 24 cycles (1 cycle = 28 days)
干预措施: Best Supportive Care (BSC) (Other)
Part 1: Venetoclax + Azacitidine (AZA) + Best Supportive Care
Participants will be administered various doses and dose regiments of venetoclax and AZA. Venetoclax will be administered once daily (QD) (Days 1-28) for up to 24 cycles, AZA QD on Days 1-5 of each 28-day cycle for up to 6 cycles and best supportive care (BSC) for 24 cycles (each cycle = 28 days)
干预措施: Venetoclax (Drug)
Part 1: Venetoclax + Azacitidine (AZA) + Best Supportive Care
Participants will be administered various doses and dose regiments of venetoclax and AZA. Venetoclax will be administered once daily (QD) (Days 1-28) for up to 24 cycles, AZA QD on Days 1-5 of each 28-day cycle for up to 6 cycles and best supportive care (BSC) for 24 cycles (each cycle = 28 days)
干预措施: Azacitidine (Drug)
Part 2: Arm A - Venetoclax + Azacitidine (AZA) + BSC
Participants will be administered with venetoclax and AZA at a dose level determined in Part 1 in addition to best supportive care (when required). Venetoclax will be administered once daily (QD) (Days 1-28) for up to 24 cycles, AZA QD on Days 1-5 of each 28-day cycle for up to 6 cycles and best supportive care (BSC) for 24 cycles (each cycle = 28 days).
干预措施: Venetoclax (Drug)
Part 2: Arm A - Venetoclax + Azacitidine (AZA) + BSC
Participants will be administered with venetoclax and AZA at a dose level determined in Part 1 in addition to best supportive care (when required). Venetoclax will be administered once daily (QD) (Days 1-28) for up to 24 cycles, AZA QD on Days 1-5 of each 28-day cycle for up to 6 cycles and best supportive care (BSC) for 24 cycles (each cycle = 28 days).
干预措施: Azacitidine (Drug)
结局指标
主要结局
Number of Participants With Dose-Limiting Toxicities (DLTs) Following Administration of Venetoclax and Azacitidine (Part 1)
时间窗: Up to the first treatment cycle (28 days)
DLTs are any of the hematologic, nonhematologic toxicities, adverse events (AEs) occurring following administration of venetoclax and AZA as described in the protocol and evaluated by the Investigator and the sponsor.
Overall Survival (OS) (Part 2)
时间窗: Up to 45 months after the first participant is randomized
OS is defined as the number of days from the date of randomization to the date of death from any cause.
次要结局
- Composite Relapse-Free Survival (RFS) (Part 2)(Up to 39 months after the first participant is randomized)
- Graft-versus-Host Disease (GvHD)-free, Relapse Free Survival (GRFS) (Part 2)(Up to 39 months after the first participant is randomized)
- Graft-versus-Host Disease (GvHD) Rate (Part 2)(Up to 39 months after the first participant is randomized)
- Change in Patient Reported Signs, Symptoms and Impact of Acute Myeloid Leukemia (AML) as Measured by the European Quality-of-Life-5 Dimensional-5-Level (EQ-5D-5L)(Up to 39 months after the first participant is randomized)
- Measurable Residual Disease (MRD) Response Rate in Participants With MRD >= 10^-3 at Randomization (Part 2)(Up to 39 months after the first participant is randomized)
- Change From Randomization in Fatigue in Adult Participants (Part 2)(Up to 39 months after the first participant is randomized)
- Change from Baseline in Physical Functioning as Measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) (Part 2)(Up to 39 months after the first participant is randomized)
- Time to Deterioration in Global Health Status (GHS)/Quality of Life (QoL) in Adult Participants (Part 2)(Up to 39 months after the first participant is randomized)
- Morphologic Relapse-Free Survival (RFS) (Part 2)(Up to 39 months after the first participant is randomized)