A Phase 2/3, Randomized, Open-Label, Comparison Study of MK-1045 Versus Blinatumomab in Participants With Relapsed or Refractory CD19+ B-Cell Acute Lymphoblastic Leukemia (B-ALL)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 340
- 试验地点
- 23
- 主要终点
- Percentage of Participants with Complete Remission (CR) in Study Part 1 and Part 2
研究概览
简要总结
Researchers are looking for new ways to treat people with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) that is CD19 positive using a medicine called MK-1045. MK-1045 is an immunotherapy, which is a treatment that helps the immune system fight cancer. This trial will compare MK-1045 to a standard immunotherapy called blinatumomab. The goals of this trial are to learn if more people who receive MK-1045 have no cancer cells in their bone marrow compared to people who receive blinatumomab and if people who receive MK-1045 live longer compared to people who receive blinatumomab.
详细描述
This study has 2 parts: Part 1 is a dose optimization phase of MK-1045. Part 2 is a randomized phase comparing the efficacy and safety of MK-1045 versus blinatumomab and will use the recommended dose of MK-1045 determined in Part 1
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
- Single (Outcomes Assessor)
盲法说明
Review of all disease response assessments in the Phase 3 component will be performed by an independent Clinical Adjudication Committee.
Reviewers will be blinded to treatment allocation and investigator assessment.
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
- •Has a confirmed diagnosis of relapsed/refractory (R/R) B-precursor acute lymphoblastic leukemia (ALL) with 5% or more lymphoblasts in the bone marrow
- •Has CD19+ disease, confirmed by local flow cytometry and/or immunohistochemistry testing at the time of enrollment
- •Has Philadelphia-negative disease, confirmed by testing, at the time of enrollment
- •Participants who have AEs due to previous anticancer therapies must have recovered to Grade ≤1 or baseline
- •Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART)
排除标准
- •Has Burkitt's leukemia
- •History or presence of clinically relevant central nervous system (CNS) diseases such as epilepsy, hemorrhagic/ischemic stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, and psychosis
- •Has active acute graft versus host disease (GvHD) or chronic GvHD. NOTE: Participants who have received CNI for GvHD within 4 weeks before the first dose of study intervention are also excluded
- •History of serious cardiovascular and cerebrovascular diseases.
- •HIV-infection with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
- •Received prior treatment with blinatumomab within 12 weeks for Part 1 and 24 weeks for Part 2 before the first dose of study intervention (individuals known to be refractory or intolerant to blinatumomab are to be excluded). Refractory to blinatumomab is defined as failure to achieve a response after at least 2 cycles of previous blinatumomab treatment
- •Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention
- •Known additional malignancy that is progressing or has required active treatment within the past 2 years
- •Isolated extramedullary disease (EMD)
- •Active autoimmune disease unrelated to ALL that has required systemic treatment in the past 2 years or history of autoimmune disease with potential CNS involvement
- •Active infection requiring systemic therapy
- •Has not adequately recovered from major surgery or have ongoing surgical complications
研究组 & 干预措施
MK-1045 Dose Regimen A
Participants will receive a lower MK-1045 dose once weekly for up to 13 cycles (two 28-day and eleven 42-day cycles). Participants will have the option to change treatment at the end of Part 1.
干预措施: MK-1045 (Biological)
Blinatumomab
Participants will receive blinatumomab on days 1, 8, 15, and 22 of each 42-day cycle
干预措施: Avtozma (Drug)
Blinatumomab
Participants will receive blinatumomab on days 1, 8, 15, and 22 of each 42-day cycle
干预措施: Tyenne (Drug)
Blinatumomab
Participants will receive blinatumomab on days 1, 8, 15, and 22 of each 42-day cycle
干预措施: Blinatumomab (Biological)
Blinatumomab
Participants will receive blinatumomab on days 1, 8, 15, and 22 of each 42-day cycle
干预措施: Dexamethasone (Drug)
MK-1045 Dose Regimen B
Participants will receive a larger MK-1045 dose once weekly for up to 13 cycles (two 28-day and eleven 42-day cycles). Participants will have the option to change treatment at the end of Part 1.
干预措施: Acetaminophen (Drug)
MK-1045 Dose Regimen B
Participants will receive a larger MK-1045 dose once weekly for up to 13 cycles (two 28-day and eleven 42-day cycles). Participants will have the option to change treatment at the end of Part 1.
干预措施: Diphenhydramine (Drug)
MK-1045 Dose Regimen A
Participants will receive a lower MK-1045 dose once weekly for up to 13 cycles (two 28-day and eleven 42-day cycles). Participants will have the option to change treatment at the end of Part 1.
干预措施: Avtozma (Drug)
MK-1045 Dose Regimen B
Participants will receive a larger MK-1045 dose once weekly for up to 13 cycles (two 28-day and eleven 42-day cycles). Participants will have the option to change treatment at the end of Part 1.
干预措施: Siltuximab (Drug)
MK-1045 Dose Regimen A
Participants will receive a lower MK-1045 dose once weekly for up to 13 cycles (two 28-day and eleven 42-day cycles). Participants will have the option to change treatment at the end of Part 1.
干预措施: Acetaminophen (Drug)
MK-1045 Dose Regimen B
Participants will receive a larger MK-1045 dose once weekly for up to 13 cycles (two 28-day and eleven 42-day cycles). Participants will have the option to change treatment at the end of Part 1.
干预措施: Tocilizumab (Drug)
MK-1045 Dose Regimen B
Participants will receive a larger MK-1045 dose once weekly for up to 13 cycles (two 28-day and eleven 42-day cycles). Participants will have the option to change treatment at the end of Part 1.
干预措施: Dexamethasone (Drug)
Blinatumomab
Participants will receive blinatumomab on days 1, 8, 15, and 22 of each 42-day cycle
干预措施: Tocilizumab (Drug)
MK-1045 Dose Regimen A
Participants will receive a lower MK-1045 dose once weekly for up to 13 cycles (two 28-day and eleven 42-day cycles). Participants will have the option to change treatment at the end of Part 1.
干预措施: Tocilizumab (Drug)
MK-1045 Dose Regimen A
Participants will receive a lower MK-1045 dose once weekly for up to 13 cycles (two 28-day and eleven 42-day cycles). Participants will have the option to change treatment at the end of Part 1.
干预措施: Dexamethasone (Drug)
Blinatumomab
Participants will receive blinatumomab on days 1, 8, 15, and 22 of each 42-day cycle
干预措施: Siltuximab (Drug)
MK-1045 Dose Regimen B
Participants will receive a larger MK-1045 dose once weekly for up to 13 cycles (two 28-day and eleven 42-day cycles). Participants will have the option to change treatment at the end of Part 1.
干预措施: MK-1045 (Biological)
MK-1045 Dose Regimen A
Participants will receive a lower MK-1045 dose once weekly for up to 13 cycles (two 28-day and eleven 42-day cycles). Participants will have the option to change treatment at the end of Part 1.
干预措施: Diphenhydramine (Drug)
MK-1045 Dose Regimen B
Participants will receive a larger MK-1045 dose once weekly for up to 13 cycles (two 28-day and eleven 42-day cycles). Participants will have the option to change treatment at the end of Part 1.
干预措施: Avtozma (Drug)
MK-1045 Dose Regimen B
Participants will receive a larger MK-1045 dose once weekly for up to 13 cycles (two 28-day and eleven 42-day cycles). Participants will have the option to change treatment at the end of Part 1.
干预措施: Tyenne (Drug)
MK-1045 Dose Regimen A
Participants will receive a lower MK-1045 dose once weekly for up to 13 cycles (two 28-day and eleven 42-day cycles). Participants will have the option to change treatment at the end of Part 1.
干预措施: Siltuximab (Drug)
MK-1045 Dose Regimen A
Participants will receive a lower MK-1045 dose once weekly for up to 13 cycles (two 28-day and eleven 42-day cycles). Participants will have the option to change treatment at the end of Part 1.
干预措施: Tyenne (Drug)
结局指标
主要结局
Percentage of Participants with Complete Remission (CR) in Study Part 1 and Part 2
时间窗: 3 treatment cycles (up to approximately 126 days; each cycle is up to 42 days; cycle lengths vary between cycle and arm)
CR is defined as: * No circulating lymphoblasts * Extramedullary disease negative * Trilineage hematopoiesis (TLH) and \<5% leukemic blasts * Absolute neutrophil count (ANC) ≥1000/μL * Platelets ≥100,000/μL * No platelet transfusions in the last 7 days * No administration of short-acting granulocyte colony-stimulating factor (G-CSF) and long-acting G-CSF in the last 3 and 14 days, respectively
Percentage of Participants Who Experience an Adverse Event (AE) in Study Part 1
时间窗: 3 treatment cycles (up to approximately 126 days; each cycle is up to 42 days; cycle lengths vary between cycle and arm)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants with at least 1 AE will be presented.
Percentage of Participants Who Discontinue Study Intervention Due to an AE in Study Part 1
时间窗: 3 treatment cycles (up to approximately 126 days; each cycle is up to 42 days; cycle lengths vary between cycle and arm)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinue study intervention due to an AE will be presented.
Overall Survival (OS) in Study Part 2
时间窗: Up to approximately 7 years
OS is the time from randomization to death due to any cause.
次要结局
- Percentage of Participants that achieve Minimal Residual Disease (MRD) in Study Part 1 and Part 2(3 treatment cycles (up to approximately 126 days; each cycle is up to 42 days; cycle lengths vary between cycle and arm))
- Percentage of Participants that achieve CR/CR with partial hematologic recovery (CRh)/CR with incomplete count recovery (CRi) in Study Part 1 and Part 2(3 treatment cycles (up to approximately 126 days; each cycle is up to 42 days; cycle lengths vary between cycle and arm))
- Percentage of Participants with CR or CRh in Study Part 2(3 treatment cycles (up to approximately 126 days; each cycle is up to 42 days; cycle lengths vary between cycle and arm))
- Overall survival (OS) in Study Part 1(Up to approximately 7 years)
- Duration of CR (DOR-CR) in Study Part 2(Up to approximately 7 years)
- Duration of CR/CRh (DOR-CR/CRh) in Study Part 2(Up to approximately 7 years)
- Duration of CR/CRh/CRi (DOR-CR/CRh/CRi) in Study Part 2(Up to approximately 7 years)
- Event Free Survival (EFS) in Study Part 2(Up to approximately 7 years)
- Percentage of participants that proceed to allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Study Part 2(Up to approximately 7 years)
- Percentage of Participants Who Experience an AE in Study Part 2(Up to approximately 7 years)
- Percentage of Participants Who Discontinue Study Intervention Due to an AE in Study Part 2(Up to approximately 7 years)