A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Study of Bleximenib, Venetoclax and Azacitidine for the Treatment of Participants With Newly Diagnosed Acute Myeloid Leukemia Harboring KMT2A Rearrangements or NPM1 Mutations Who Are Ineligible for Intensive Chemotherapy
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 600
- 试验地点
- 267
- 主要终点
- Percentage of Participants who Achieve Complete Remission (CR)
研究概览
简要总结
The purpose of this study is to assess how bleximenib and Venetoclax (VEN)+ Azacitidine (AZA) works as compared to placebo and VEN+AZA alone for the treatment of participants with newly diagnosed Acute Myeloid Leukemia (AML) with a mutation in the NPM1 or KMT2A gene.
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
- Triple (Participant, 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
- •Be 18 years of age or older at the time of informed consent
- •Previously untreated lysine N-methyltransferase 2A gene rearranged (KMT2Ar) or nucleophosmin 1 gene mutated (NPM1m) acute myeloid leukemia (AML) with greater than or equal to (> or =) 10% bone marrow blasts per 2022 international Consensus Classification criteria
- •Ineligible for intensive chemotherapy based on the following criteria: a) >= 75 years of age and ineligible per physician's discretion, with Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, b) >=18 to <75 years of age with >= 1 of the following comorbidities: i) ECOG performance status of 2, ii) Severe cardiac disorder, iii) Severe pulmonary disorder, iv) Renal impairment, v) Moderate hepatic impairment vi) Comorbidity that, in the investigator's opinion, makes the participant unsuitable for intensive chemotherapy, which must be documented before enrollment as defined in the protocol. Ineligibility for intensive chemotherapy should be explicitly approved by a multidisciplinary team in countries in which this process is standard of care
- •Participants must have adequate hepatic and renal function
- •A female participant must agree not to be pregnant, breast-feed, plan to become pregnant and use protocol-specified contraception while enrolled in this study and for 6 months after the last dose of study treatment
- •A male participant must agree to use protocol-specified contraception while enrolled in this study for at least 90 days after the last dose of study treatment
- •Must sign an informed consent form indicating that the participant understands the purpose of, and procedures required for, the study and is willing to participate in the study
排除标准
- •Diagnosis of acute promyelocytic leukemia (APL)
- •Known active leukemic involvement of the central nervous system (CNS)
- •Recipient of solid organ transplant
- •Any cardiac disorders such as heart attack, uncontrolled/unstable chest pain, congestive heart failure, uncontrolled or symptomatic irregular heartbeat, blockage of a blood vessel to brain, or transient ischemic (decreased oxygen in tissue) attack within 6 months of randomization
- •Active infectious hepatitis
- •Live, attenuated vaccine within 4 weeks of randomization
- •Known allergies, hypersensitivity, or intolerance of bleximenib, azacitidine, or venetoclax excipients
研究组 & 干预措施
Arm B: Placebo and Venetoclax (VEN) + Azacitidine (AZA)
Participants with AML will receive placebo in combination with VEN and AZA for 28-days treatment cycles, and treatment will continue until progression or unacceptable toxicity.
干预措施: Azacitidine (AZA) (Drug)
Arm A: Bleximenib and Venetoclax (VEN) + Azacitidine (AZA)
Participants with acute myeloid leukemia (AML) will receive bleximenib in combination with venetoclax (VEN) and azacitidine (AZA) for 28-days treatment cycles and treatment will continue until progression or unacceptable toxicity.
干预措施: Bleximenib (Drug)
Arm A: Bleximenib and Venetoclax (VEN) + Azacitidine (AZA)
Participants with acute myeloid leukemia (AML) will receive bleximenib in combination with venetoclax (VEN) and azacitidine (AZA) for 28-days treatment cycles and treatment will continue until progression or unacceptable toxicity.
干预措施: Venetoclax (VEN) (Drug)
Arm B: Placebo and Venetoclax (VEN) + Azacitidine (AZA)
Participants with AML will receive placebo in combination with VEN and AZA for 28-days treatment cycles, and treatment will continue until progression or unacceptable toxicity.
干预措施: Placebo (Drug)
Arm B: Placebo and Venetoclax (VEN) + Azacitidine (AZA)
Participants with AML will receive placebo in combination with VEN and AZA for 28-days treatment cycles, and treatment will continue until progression or unacceptable toxicity.
干预措施: Venetoclax (VEN) (Drug)
Arm A: Bleximenib and Venetoclax (VEN) + Azacitidine (AZA)
Participants with acute myeloid leukemia (AML) will receive bleximenib in combination with venetoclax (VEN) and azacitidine (AZA) for 28-days treatment cycles and treatment will continue until progression or unacceptable toxicity.
干预措施: Azacitidine (AZA) (Drug)
结局指标
主要结局
Percentage of Participants who Achieve Complete Remission (CR)
时间窗: Up to 4 years and 1 month
CR is defined as Bone marrow blasts less than (\<) 5 percent (%); Absence of circulating blasts; Absence of extramedullary disease; Absolute neutrophil count (ANC) greater than or equal to (\>=) 1.0 \* 10\^9/Liter (1,000/microliter \[mcL\]); Platelet count \>= 100 \* 10\^9/L (100,000/mcL).
Overall Survival (OS)
时间窗: Up to 4 years and 1 month
Overall survival time is defined as the time duration from the date of randomization to death due to any cause.
Percentage of Participants who Achieve Complete Remission (CR)
时间窗: Up to 4 years and 1 month
CR is defined as Bone marrow blasts less than (\<) 5 percent (%); Absence of circulating blasts; Absence of extramedullary disease; Absolute neutrophil count (ANC) greater than or equal to (\>=) 1.0 \* 10\^9/Liter (1,000/microliter \[mcL\]); Platelet count \>= 100 \* 10\^9/L (100,000/mcL).
Overall Survival (OS)
时间窗: Up to 4 years and 1 month
Overall survival time is defined as the time duration from the date of randomization to death due to any cause.
次要结局
- Event-free survival (EFS)(Up to 4 years and 1 month)
- Duration of CR(Up to 4 years and 1 month)
- Time to CR(Up to 4 years and 1 month)
- Percentage of Participants who Achieved Transfusion Independence(Up to 4 years and 1 month)
- Percentage of Participants with Allogeneic Hematopoietic Stem Cell Transplant (Allo-HSCT)(Up to 4 years and 1 month)
- Number of Participants with Adverse Events (AEs)(Up to 4 years and 1 month)
- Number of Participants with Abnormalities in Clinical Laboratory Parameters(Up to 4 years and 1 month)
- Serum Concentration of Bleximenib(Up to 4 years and 1 month)
- Event-free survival (EFS)(Up to 4 years and 1 month)
- Duration of CR(Up to 4 years and 1 month)
- Time to CR(Up to 4 years and 1 month)
- Rate of CR Without Measurable Residual Disease (MRD-)(Up to 4 years and 1 month)
- Percentage of Participants who Achieved Transfusion Independence(Up to 4 years and 1 month)
- Percentage of Participants with Allogeneic Hematopoietic Stem Cell Transplant (Allo-HSCT)(Up to 4 years and 1 month)
- Number of Participants with Adverse Events (AEs)(Up to 4 years and 1 month)
- Number of Participants with Abnormalities in Clinical Laboratory Parameters(Up to 4 years and 1 month)
- Serum Concentration of Bleximenib(Up to 4 years and 1 month)