Bleximenib or Placebo in Combination With Standard Induction and Consolidation Therapy Followed by Maintenance for the Treatment of Patients With Newly Diagnosed KMT2A-rearranged or NPM1-mutant Acute Myeloid Leukemia Eligible for Intensive Chemotherapy: a Double-blind Phase 3 Study
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 875
- 试验地点
- 82
- 主要终点
- Event-Free Survival (EFS) in adult patients with newly diagnosed NPM1m or KMT2Ar AML eligible for intensive chemotherapy
研究概览
简要总结
The current standard of care treatment for adult patients with acute myeloid leukemia (AML) consists of chemotherapy and, if indicated, donor stem cell transplantation.
Bleximenib blocks the interaction between a protein called menin and another protein called KMT2A in the leukemia cells. When this interaction is disrupted in AML with mutations in the NPM1 or KMT2A gene, bleximenib can cause leukemia cells to die.
The main objective is to assess if treatment with bleximenib, when added to chemotherapy treatment will improve treatment outcome in adult participants with newly diagnosed AML who present with mutations in the NPM1 or KMT2A genes.
This is a randomized, double-blind, placebo-controlled, phase 3 clinical trial. All of the participants will receive standard chemotherapy treatment, combined with either bleximenib or a placebo. A placebo is a substance that looks like the study medicine but has no active ingredients (e.g., a sugar pill). In a double blind trial neither the participant nor the doctor know if placebo or active study drug is given.
After the end of the protocol treatment there will be an observational follow-up of 4 years from the time of inclusion of the last patient. The results of the different treatment groups will be compared.
875 previously untreated patients with AML with a specific change in the DNA of the leukemia cells (a KMT2A rearrangement or a NPM1 mutation) will be included. Participants must be 18 years or older and considered eligible for intensive chemotherapy.
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
- Double (Participant, Investigator)
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
- •≥18 years of age (or the legal age of majority in the jurisdiction in which the study is taking place, whichever is greater) at the time of informed consent.
- •New diagnosis of AML (≥10% blasts in BM or peripheral blood) with mutated NPM1 or with recurring rearrangements involving KMT2A according to ICC 2022 criteria.
- •Considered eligible for intensive chemotherapy.
- •WHO/ECOG performance status ≤
- •Adequate renal and hepatic functions prior to randomization.
排除标准
- •Prior (chemo-)therapy for AML, including prior treatment with hypomethylating agents
- •Known active leukemic involvement of the central nervous system (CNS).
- •Recipient of solid organ transplant.
- •Cardiac disease:
- •Any of the following within 6 months of randomization: myocardial infarction, uncontrolled/unstable angina, congestive heart failure (NYHA Class III or IV), uncontrolled or symptomatic arrhythmias, stroke, or transient ischemic attack.
- •QTc interval using Fridericia's formula (QTcF) ≥470 ms. Prolonged QTc interval associated with bundle branch block or pacemaking is permitted.
- •Left ventricular ejection fraction (LVEF) <40% by ECHO or MUGA scan obtained within 28 days prior to the start of study treatment.
- •Previously received cumulative dose of any combination of anthracyclines or anthracenediones of ≥500 mg/m
- •Chronic respiratory disease requiring supplemental oxygen.
研究组 & 干预措施
Arm 2: Standard of care treatment plus bleximenib and maintenance treatment with a placebo.
Bleximenib in combination with remission induction and consolidation therapy, followed by placebo maintenance therapy. Treatment will continue until PD, unacceptable toxicity or other protocol defined criteria for discontinuation (whichever comes first)
干预措施: Cytarabine (Drug)
Arm 3: Standard of care treatment plus a placebo and maintenance treatment with a placebo.
Placebo comparator in combination with remission induction and consolidation therapy, followed by placebo maintenance therapy . Treatment will continue until PD, unacceptable toxicity or other protocol defined criteria for discontinuation (whichever comes first)
干预措施: Cytarabine (Drug)
Arm 3: Standard of care treatment plus a placebo and maintenance treatment with a placebo.
Placebo comparator in combination with remission induction and consolidation therapy, followed by placebo maintenance therapy . Treatment will continue until PD, unacceptable toxicity or other protocol defined criteria for discontinuation (whichever comes first)
干预措施: Placebo (Drug)
Arm 1: Standard of care treatment plus bleximenib and also maintenance treatment with bleximenib
Bleximenib in combination with remission induction and consolidation therapy, followed by bleximenib maintenance therapy. Treatment will continue until PD, unacceptable toxicity or other protocol defined criteria for discontinuation (whichever comes first)
干预措施: Cytarabine (Drug)
Arm 1: Standard of care treatment plus bleximenib and also maintenance treatment with bleximenib
Bleximenib in combination with remission induction and consolidation therapy, followed by bleximenib maintenance therapy. Treatment will continue until PD, unacceptable toxicity or other protocol defined criteria for discontinuation (whichever comes first)
干预措施: Bleximenib (Drug)
Arm 2: Standard of care treatment plus bleximenib and maintenance treatment with a placebo.
Bleximenib in combination with remission induction and consolidation therapy, followed by placebo maintenance therapy. Treatment will continue until PD, unacceptable toxicity or other protocol defined criteria for discontinuation (whichever comes first)
干预措施: Placebo (Drug)
Arm 2: Standard of care treatment plus bleximenib and maintenance treatment with a placebo.
Bleximenib in combination with remission induction and consolidation therapy, followed by placebo maintenance therapy. Treatment will continue until PD, unacceptable toxicity or other protocol defined criteria for discontinuation (whichever comes first)
干预措施: Bleximenib (Drug)
Arm 3: Standard of care treatment plus a placebo and maintenance treatment with a placebo.
Placebo comparator in combination with remission induction and consolidation therapy, followed by placebo maintenance therapy . Treatment will continue until PD, unacceptable toxicity or other protocol defined criteria for discontinuation (whichever comes first)
干预措施: Daunorubicin or Idarubicin (Drug)
Arm 1: Standard of care treatment plus bleximenib and also maintenance treatment with bleximenib
Bleximenib in combination with remission induction and consolidation therapy, followed by bleximenib maintenance therapy. Treatment will continue until PD, unacceptable toxicity or other protocol defined criteria for discontinuation (whichever comes first)
干预措施: Daunorubicin or Idarubicin (Drug)
Arm 2: Standard of care treatment plus bleximenib and maintenance treatment with a placebo.
Bleximenib in combination with remission induction and consolidation therapy, followed by placebo maintenance therapy. Treatment will continue until PD, unacceptable toxicity or other protocol defined criteria for discontinuation (whichever comes first)
干预措施: Daunorubicin or Idarubicin (Drug)
结局指标
主要结局
Event-Free Survival (EFS) in adult patients with newly diagnosed NPM1m or KMT2Ar AML eligible for intensive chemotherapy
时间窗: Up to 4 years and 5 months
To assess if treatment with bleximenib, as compared with placebo, in combination with remission induction chemotherapy, prolongs event-free survival (EFS) measured from the time from randomization to failure to achieve CR after remission induction, hematologic relapse after achieving CR, or death, whichever occurs first.
次要结局
- Overall Survival (OS) in adult patients with newly diagnosed NPM1m or KMT2Ar AML eligible for intensive chemotherapy(Up to 7 years and 10 months)
- Rates of CR, CRh, CRi in adult patients with newly diagnosed NPM1m or KMT2Ar AML eligible for intensive chemotherapy(Up to 7 years and 10 months)
- Prolongation of CR (DoCR) in adult patients with newly diagnosed NPM1m or KMT2Ar AML eligible for intensive chemotherapy(Up to 4 years and 5 months)
- Percentage of participants undergoing an allo-SCT in adult patients with newly diagnosed NPM1m or KMT2Ar AML eligible for intensive chemotherapy(Up to 7 years and 10 months)