A Randomized Phase II/III Study of Conventional Chemotherapy +/- Uproleselan (GMI-1271) in Older Adults With Acute Myeloid Leukemia Receiving Intensive Induction Chemotherapy
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 267
- 试验地点
- 188
- 主要终点
- Overall survival (OS) (Phase III)
研究概览
简要总结
This phase II/III trial studies how well daunorubicin and cytarabine with or without uproleselan works in treating older adult patients with acute myeloid leukemia receiving intensive induction chemotherapy. Drugs used in chemotherapy, such as daunorubicin and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Uproleselan may prevent cancer from returning or getting worse. Giving daunorubicin and cytarabine with uproleselan may work better in treating patients with acute myeloid leukemia compared to daunorubicin and cytarabine alone.
详细描述
PRIMARY OBJECTIVES:
I. Compare the event-free survival (EFS) of daunorubicin, cytarabine plus uproleselan versus daunorubicin and cytarabine in subjects >= age 60 with previously untreated acute myeloid leukemia. (Phase II) II. Compare the overall survival (OS) of the daunorubicin, cytarabine plus uproleselan to daunorubicin and cytarabine in this patient population. (Phase III)
SECONDARY OBJECTIVES:
I. Determine the rates of complete remission (CR), complete remission with incomplete count recovery (CRi), complete remission with incomplete hematopoietic recovery (CRh) and cytogenetic complete remission (CCyR) for each chemotherapy regimen.
II. Determine the overall survival (OS), and remission duration of patients for each chemotherapy regimen.
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
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of acute myeloid leukemia (AML) based on 2017 World Health Organization (WHO) criteria excluding acute promyelocytic leukemia with PML-RARA.
- •Note: Patients with myeloid sarcoma without bone marrow involvement, acute leukemia of ambiguous lineage or blast transformation of chronic myelogenous leukemia (CML) are not eligible.
- •No activating mutation in the Fms-like tyrosine kinase-3 (FLT3) defined as a ratio of mutant to wild-type allele >= 0.05 by capillary electrophoresis or a variant allele fraction of >= 5% by next generation sequencing from either bone marrow or peripheral blood.
- •No evidence of central nervous system (CNS) involvement of AML.
- •No prior chemotherapy for myelodysplastic syndrome (MDS), myeloproliferative neoplasm (MPN) or AML including hypomethylating agents (e.g. azacitidine and decitabine), ruxolitinib or lenalidomide with the following exceptions:
- •Emergency leukapheresis
- •Hydroxyurea
- •Growth factor/cytokine support
- •All-trans retinoic acid (ATRA)
- •Single dose of intrathecal cytarabine and/or methotrexate for patients undergoing lumbar puncture to evaluate for CNS involvement.
- •Age >= 60 years.
- •Total bilirubin =< 3 x upper limit of normal (ULN)
- •Creatinine < 3 x upper limit of normal (ULN) OR creatinine clearance >= 30 mL/min/1.73m^2
排除标准
- 未提供
研究组 & 干预措施
Arm I (daunorubicin, cytarabine)
INDUCTION: Patients receive daunorubicin IV on days 1-3 and cytarabine via CIVI over 168 hours on days 1-7. Patients with residual disease indicated by bone marrow examination receive a second induction including daunorubicin IV on days 1-2 and cytarabine CIVI over 12 hours on days 1-5.
CONSOLIDATION: Patients receive cytarabine IV over 3 hours on days 1-5. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Additionally, all patients undergo MUGA or ECHO during baseline, and bone marrow aspirate, bone marrow biopsy, and blood collection throughout the study.
干预措施: Biospecimen Collection (Procedure)
Arm I (daunorubicin, cytarabine)
INDUCTION: Patients receive daunorubicin IV on days 1-3 and cytarabine via CIVI over 168 hours on days 1-7. Patients with residual disease indicated by bone marrow examination receive a second induction including daunorubicin IV on days 1-2 and cytarabine CIVI over 12 hours on days 1-5.
CONSOLIDATION: Patients receive cytarabine IV over 3 hours on days 1-5. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Additionally, all patients undergo MUGA or ECHO during baseline, and bone marrow aspirate, bone marrow biopsy, and blood collection throughout the study.
干预措施: Bone Marrow Aspiration (Procedure)
Arm I (daunorubicin, cytarabine)
INDUCTION: Patients receive daunorubicin IV on days 1-3 and cytarabine via CIVI over 168 hours on days 1-7. Patients with residual disease indicated by bone marrow examination receive a second induction including daunorubicin IV on days 1-2 and cytarabine CIVI over 12 hours on days 1-5.
CONSOLIDATION: Patients receive cytarabine IV over 3 hours on days 1-5. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Additionally, all patients undergo MUGA or ECHO during baseline, and bone marrow aspirate, bone marrow biopsy, and blood collection throughout the study.
干预措施: Bone Marrow Biopsy (Procedure)
Arm I (daunorubicin, cytarabine)
INDUCTION: Patients receive daunorubicin IV on days 1-3 and cytarabine via CIVI over 168 hours on days 1-7. Patients with residual disease indicated by bone marrow examination receive a second induction including daunorubicin IV on days 1-2 and cytarabine CIVI over 12 hours on days 1-5.
CONSOLIDATION: Patients receive cytarabine IV over 3 hours on days 1-5. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Additionally, all patients undergo MUGA or ECHO during baseline, and bone marrow aspirate, bone marrow biopsy, and blood collection throughout the study.
干预措施: Cytarabine (Drug)
Arm I (daunorubicin, cytarabine)
INDUCTION: Patients receive daunorubicin IV on days 1-3 and cytarabine via CIVI over 168 hours on days 1-7. Patients with residual disease indicated by bone marrow examination receive a second induction including daunorubicin IV on days 1-2 and cytarabine CIVI over 12 hours on days 1-5.
CONSOLIDATION: Patients receive cytarabine IV over 3 hours on days 1-5. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Additionally, all patients undergo MUGA or ECHO during baseline, and bone marrow aspirate, bone marrow biopsy, and blood collection throughout the study.
干预措施: Daunorubicin (Drug)
Arm I (daunorubicin, cytarabine)
INDUCTION: Patients receive daunorubicin IV on days 1-3 and cytarabine via CIVI over 168 hours on days 1-7. Patients with residual disease indicated by bone marrow examination receive a second induction including daunorubicin IV on days 1-2 and cytarabine CIVI over 12 hours on days 1-5.
CONSOLIDATION: Patients receive cytarabine IV over 3 hours on days 1-5. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Additionally, all patients undergo MUGA or ECHO during baseline, and bone marrow aspirate, bone marrow biopsy, and blood collection throughout the study.
干预措施: Echocardiography Test (Procedure)
Arm I (daunorubicin, cytarabine)
INDUCTION: Patients receive daunorubicin IV on days 1-3 and cytarabine via CIVI over 168 hours on days 1-7. Patients with residual disease indicated by bone marrow examination receive a second induction including daunorubicin IV on days 1-2 and cytarabine CIVI over 12 hours on days 1-5.
CONSOLIDATION: Patients receive cytarabine IV over 3 hours on days 1-5. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Additionally, all patients undergo MUGA or ECHO during baseline, and bone marrow aspirate, bone marrow biopsy, and blood collection throughout the study.
干预措施: Multigated Acquisition Scan (Procedure)
Arm II (uproleselan, daunorubicin, cytarabine)
INDUCTION: Patients receive uproleselan IV QD on day 1 and then every 12 hours on days 2-10. Patients also receive daunorubicin IV on days 2-4 and cytrarabine CIVI over 168 hours on days 2-8 over 168 hours. Patients with residual disease indicated by bone marrow examination receive a second induction including uprleselan IV QD on day 1 and then every 12 hours on days 2-8, daunorubicin IV on days 2-3, and cytarabine CIVI over 120 hours on days 2-6.
CONSOLIDATION: Patients who achieve a CR or CRi receive uproleselan IV QD on day 1 and every 12 hours on days 2-8 and cytarabine IV over 3 hours on days 2-6. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Additionally, all patients undergo MUGA or ECHO during baseline, and bone marrow aspirate, bone marrow biopsy, and blood collection throughout the study.
干预措施: Biospecimen Collection (Procedure)
Arm II (uproleselan, daunorubicin, cytarabine)
INDUCTION: Patients receive uproleselan IV QD on day 1 and then every 12 hours on days 2-10. Patients also receive daunorubicin IV on days 2-4 and cytrarabine CIVI over 168 hours on days 2-8 over 168 hours. Patients with residual disease indicated by bone marrow examination receive a second induction including uprleselan IV QD on day 1 and then every 12 hours on days 2-8, daunorubicin IV on days 2-3, and cytarabine CIVI over 120 hours on days 2-6.
CONSOLIDATION: Patients who achieve a CR or CRi receive uproleselan IV QD on day 1 and every 12 hours on days 2-8 and cytarabine IV over 3 hours on days 2-6. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Additionally, all patients undergo MUGA or ECHO during baseline, and bone marrow aspirate, bone marrow biopsy, and blood collection throughout the study.
干预措施: Bone Marrow Aspiration (Procedure)
Arm II (uproleselan, daunorubicin, cytarabine)
INDUCTION: Patients receive uproleselan IV QD on day 1 and then every 12 hours on days 2-10. Patients also receive daunorubicin IV on days 2-4 and cytrarabine CIVI over 168 hours on days 2-8 over 168 hours. Patients with residual disease indicated by bone marrow examination receive a second induction including uprleselan IV QD on day 1 and then every 12 hours on days 2-8, daunorubicin IV on days 2-3, and cytarabine CIVI over 120 hours on days 2-6.
CONSOLIDATION: Patients who achieve a CR or CRi receive uproleselan IV QD on day 1 and every 12 hours on days 2-8 and cytarabine IV over 3 hours on days 2-6. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Additionally, all patients undergo MUGA or ECHO during baseline, and bone marrow aspirate, bone marrow biopsy, and blood collection throughout the study.
干预措施: Bone Marrow Biopsy (Procedure)
Arm II (uproleselan, daunorubicin, cytarabine)
INDUCTION: Patients receive uproleselan IV QD on day 1 and then every 12 hours on days 2-10. Patients also receive daunorubicin IV on days 2-4 and cytrarabine CIVI over 168 hours on days 2-8 over 168 hours. Patients with residual disease indicated by bone marrow examination receive a second induction including uprleselan IV QD on day 1 and then every 12 hours on days 2-8, daunorubicin IV on days 2-3, and cytarabine CIVI over 120 hours on days 2-6.
CONSOLIDATION: Patients who achieve a CR or CRi receive uproleselan IV QD on day 1 and every 12 hours on days 2-8 and cytarabine IV over 3 hours on days 2-6. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Additionally, all patients undergo MUGA or ECHO during baseline, and bone marrow aspirate, bone marrow biopsy, and blood collection throughout the study.
干预措施: Cytarabine (Drug)
Arm II (uproleselan, daunorubicin, cytarabine)
INDUCTION: Patients receive uproleselan IV QD on day 1 and then every 12 hours on days 2-10. Patients also receive daunorubicin IV on days 2-4 and cytrarabine CIVI over 168 hours on days 2-8 over 168 hours. Patients with residual disease indicated by bone marrow examination receive a second induction including uprleselan IV QD on day 1 and then every 12 hours on days 2-8, daunorubicin IV on days 2-3, and cytarabine CIVI over 120 hours on days 2-6.
CONSOLIDATION: Patients who achieve a CR or CRi receive uproleselan IV QD on day 1 and every 12 hours on days 2-8 and cytarabine IV over 3 hours on days 2-6. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Additionally, all patients undergo MUGA or ECHO during baseline, and bone marrow aspirate, bone marrow biopsy, and blood collection throughout the study.
干预措施: Daunorubicin (Drug)
Arm II (uproleselan, daunorubicin, cytarabine)
INDUCTION: Patients receive uproleselan IV QD on day 1 and then every 12 hours on days 2-10. Patients also receive daunorubicin IV on days 2-4 and cytrarabine CIVI over 168 hours on days 2-8 over 168 hours. Patients with residual disease indicated by bone marrow examination receive a second induction including uprleselan IV QD on day 1 and then every 12 hours on days 2-8, daunorubicin IV on days 2-3, and cytarabine CIVI over 120 hours on days 2-6.
CONSOLIDATION: Patients who achieve a CR or CRi receive uproleselan IV QD on day 1 and every 12 hours on days 2-8 and cytarabine IV over 3 hours on days 2-6. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Additionally, all patients undergo MUGA or ECHO during baseline, and bone marrow aspirate, bone marrow biopsy, and blood collection throughout the study.
干预措施: Echocardiography Test (Procedure)
Arm II (uproleselan, daunorubicin, cytarabine)
INDUCTION: Patients receive uproleselan IV QD on day 1 and then every 12 hours on days 2-10. Patients also receive daunorubicin IV on days 2-4 and cytrarabine CIVI over 168 hours on days 2-8 over 168 hours. Patients with residual disease indicated by bone marrow examination receive a second induction including uprleselan IV QD on day 1 and then every 12 hours on days 2-8, daunorubicin IV on days 2-3, and cytarabine CIVI over 120 hours on days 2-6.
CONSOLIDATION: Patients who achieve a CR or CRi receive uproleselan IV QD on day 1 and every 12 hours on days 2-8 and cytarabine IV over 3 hours on days 2-6. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Additionally, all patients undergo MUGA or ECHO during baseline, and bone marrow aspirate, bone marrow biopsy, and blood collection throughout the study.
干预措施: Multigated Acquisition Scan (Procedure)
Arm II (uproleselan, daunorubicin, cytarabine)
INDUCTION: Patients receive uproleselan IV QD on day 1 and then every 12 hours on days 2-10. Patients also receive daunorubicin IV on days 2-4 and cytrarabine CIVI over 168 hours on days 2-8 over 168 hours. Patients with residual disease indicated by bone marrow examination receive a second induction including uprleselan IV QD on day 1 and then every 12 hours on days 2-8, daunorubicin IV on days 2-3, and cytarabine CIVI over 120 hours on days 2-6.
CONSOLIDATION: Patients who achieve a CR or CRi receive uproleselan IV QD on day 1 and every 12 hours on days 2-8 and cytarabine IV over 3 hours on days 2-6. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Additionally, all patients undergo MUGA or ECHO during baseline, and bone marrow aspirate, bone marrow biopsy, and blood collection throughout the study.
干预措施: Uproleselan (Drug)
结局指标
主要结局
Overall survival (OS) (Phase III)
时间窗: Up to 5 years
Will be measured from the date of randomization to death from any cause, with patients last known to be alive censored at the date of last contact.
Event-free survival (EFS) (Phase II)
时间窗: Up to 5 years
EFS is defined as the time from the date of randomization to the first of failure to achieve a complete remission (CR)/ CR with incomplete blood count recovery (CRi) during induction, relapse, or death due to any cause, with patients last known to be alive and event-free censored at the date of last contact.
次要结局
- Impact of off-protocol transplantation(Up to 5 years)
- Consistency of the treatment effect among each subgroup(From baseline up to 5 years)
- EFS rate(Up to 1 year)
- Disease-free survival (DFS)(Time from achieving a complete response to time of relapse or death, assessed up to 5 years)
- Complete remission (CR) and overall response rate(Up to 5 years)
- Prediction of CR, EFS, DFS, and OS by pretreatment characteristics such as age, morphology, cytogenetics, immunophenotype, molecular genetic features, WBC count and hemogram, and performance status with clinical outcomes(Up to 5 years)
- Incidence of adverse events(Up to 5 years)