A Phase 3, Double-Blind, Randomized, Placebo-Controlled Trial Of Quizartinib Administered in Combination With Induction and Consolidation Chemotherapy and Administered as Maintenance Therapy in Adult Patients With Newly Diagnosed FLT3-ITD Negative Acute Myeloid Leukemia
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 700
- 试验地点
- 496
- 主要终点
- Overall Survival (Arm A vs Arm B)
研究概览
简要总结
This study will compare the effects of Quizartinib versus placebo in combination with chemotherapy in participants with newly diagnosed FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) negative acute myeloid leukemia (AML).
详细描述
This is a clinical trial to compare the effect of quizartinib versus placebo (administered with standard induction and consolidation chemotherapy, then administered as maintenance therapy for up to 36 cycles) on the primary endpoint of overall survival (OS) in adult patients with newly diagnosed FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) negative acute myeloid leukemia (AML). Participants will be tested for FLT3-ITD mutation status in a central laboratory using a validated assay.
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, Care Provider, Investigator)
盲法说明
This study has a double-blind design. Neither the participants nor any of the investigators, Sponsor, Independent Review Committee (IRC) or contract research organizations (CROs) will be aware of the treatments received. An independent biostatistician, not otherwise part of the Sponsor trial team, will generate the randomization schedule.
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must be competent and able to comprehend, sign, and date an Ethics Committee (EC)- or Institutional Review Board (IRB)-approved ICF before performance of any trial-specific procedures or tests.
- •≥18 years or the minimum legal adult age (whichever is greater) and ≤70 years (at Screening).
- •Newly diagnosed, morphologically documented primary AML based on the World Health Organization (WHO) 2016 classification (at Screening)
- •Eastern Cooperative Oncology Group (ECOG) performance status (at the time the participant signs their ICF) of 0-
- •Participant is a candidate for standard "7+3" induction chemotherapy regimen as specified in the protocol per investigator assessment
排除标准
- •Diagnosis of acute promyelocytic leukemia (APL), French-American-British classification M3 or WHO classification of APL with translocation, t(15;17)(q22;q12), or BCR-ABL positive leukemia (ie, chronic myelogenous leukemia in blast crisis); participants who undergo diagnostic workup for APL and treatment with all-trans retinoic acid (ATRA), but who are found not to have APL, are eligible (treatment with ATRA must be discontinued before starting induction chemotherapy).
- •Diagnosis of AML secondary to prior chemotherapy or radiotherapy.
- •Diagnosis of AML with known antecedent myelodysplastic syndrome (MDS) or a myeloproliferative neoplasm (MPN) or MDS/MPNs including chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia (aCML), juvenile myelomonocytic leukemia (JMML) and others.
- •Participants with newly diagnosed AML with FLT3-ITD mutations (FLT3-ITD [+]) present at ≥5% VAF (or ≥0.05 SR) based on a validated FLT3 mutation assay.
- •Prior treatment for AML, except for the following allowances prior to Day 1 of chemotherapy:
- •Leukapheresis;
- •Treatment for hyperleukocytosis with hydroxyurea;
- •Cranial radiotherapy for central nervous system (CNS) leukostasis;
- •Prophylactic intrathecal chemotherapy
研究组 & 干预措施
Arm A: Quizartinib + Chemotherapy
Participants will receive quizartinib at 60 mg/day orally once daily for 14 days starting after the completion of chemotherapy in Induction and Consolidation Phase. In the Maintenance Phase, participants will receive quizartinib at 60 mg/day orally once daily for up to 36 cycles (28-day cycle)
干预措施: Chemotherapy (Drug)
Arm B: Placebo + Chemotherapy
Participants will receive placebo at 60 mg/day orally once daily for 14 days starting after the completion of chemotherapy in Induction and Consolidation Phase. In the Maintenance Phase, participants will receive placebo at 60 mg/day orally once daily for up to 36 cycles (28-day cycle)
干预措施: Placebo (Drug)
Arm C: Quizartinib + Chemotherapy then Placebo Maintenance
Participants will receive quizartinib at 60 mg/day orally once daily for 14 days starting after the completion of chemotherapy in Induction and Consolidation Phase. In the Maintenance Phase, participants will receive placebo at 60 mg/day orally once daily for up to 36 cycles (28-day cycle)
干预措施: Quizartinib (Drug)
Arm B: Placebo + Chemotherapy
Participants will receive placebo at 60 mg/day orally once daily for 14 days starting after the completion of chemotherapy in Induction and Consolidation Phase. In the Maintenance Phase, participants will receive placebo at 60 mg/day orally once daily for up to 36 cycles (28-day cycle)
干预措施: Chemotherapy (Drug)
Arm C: Quizartinib + Chemotherapy then Placebo Maintenance
Participants will receive quizartinib at 60 mg/day orally once daily for 14 days starting after the completion of chemotherapy in Induction and Consolidation Phase. In the Maintenance Phase, participants will receive placebo at 60 mg/day orally once daily for up to 36 cycles (28-day cycle)
干预措施: Placebo (Drug)
Arm C: Quizartinib + Chemotherapy then Placebo Maintenance
Participants will receive quizartinib at 60 mg/day orally once daily for 14 days starting after the completion of chemotherapy in Induction and Consolidation Phase. In the Maintenance Phase, participants will receive placebo at 60 mg/day orally once daily for up to 36 cycles (28-day cycle)
干预措施: Chemotherapy (Drug)
Arm A: Quizartinib + Chemotherapy
Participants will receive quizartinib at 60 mg/day orally once daily for 14 days starting after the completion of chemotherapy in Induction and Consolidation Phase. In the Maintenance Phase, participants will receive quizartinib at 60 mg/day orally once daily for up to 36 cycles (28-day cycle)
干预措施: Quizartinib (Drug)
结局指标
主要结局
Overall Survival (Arm A vs Arm B)
时间窗: Date of first patient randomized to the target number of deaths reached, up to approximately 42 months
Overall survival (OS) is defined as the time from randomization until death from any cause.
次要结局
- Event-free survival (Arm A vs. Arm B)(Date of randomization up to approximately 42 months)
- Duration of complete response (Arm A vs. Arm B)(Date of randomization up to approximately 42 months)
- Relapse-free survival (Arm A vs. Arm B)(Date of randomization up to approximately 42 months)
- Complete remission rate (Arm A vs. Arm B)(At end of Induction Phase, up to approximately 120 days)
- Number of Participants With Treatment-emergent Adverse Events (Arm A vs. Arm B)(Date of first dose up to 30 days after last dose, up to approximately 42 months)
- Event-free survival (Arm A vs. Arm B)(Date of randomization up to approximately 42 months)
- Duration of complete response (Arm A vs. Arm B)(Date of randomization up to approximately 42 months)
- Relapse-free survival (Arm A vs. Arm B)(Date of randomization up to approximately 42 months)
- Complete remission rate (Arm A vs. Arm B)(At end of Induction Phase, up to approximately 120 days)
- Complete remission rate with minimal or measurable residual disease (Arm A vs. Arm B)(At end of Induction Phase (Cycle 2 or Cycles 1 and 2), up to approximately 120 days)
- Number of Participants With Treatment-emergent Adverse Events (Arm A vs. Arm B)(Date of first dose up to 30 days after last dose, up to approximately 42 months)