A Phase III Randomized Trial for Patients With De Novo AML Using Bortezomib and Sorafenib (NSC# 681239, NSC# 724772) for Patients With High Allelic Ratio FLT3/ITD
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,645
- 试验地点
- 440
- 主要终点
- EFS for Patients on Arm C, Cohort 3
研究概览
简要总结
This randomized phase III trial studies how well bortezomib and sorafenib tosylate work in treating patients with newly diagnosed acute myeloid leukemia. Bortezomib and sorafenib tosylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving bortezomib and sorafenib tosylate together with combination chemotherapy may be an effective treatment for acute myeloid leukemia.
详细描述
PRIMARY OBJECTIVES:
I. To compare event-free survival (EFS) and overall survival (OS) in patients with de novo acute myeloid leukemia (AML) without high allelic ratio fms-like tyrosine kinase (FLT3)/internal tandem duplications (ITD)+ mutations who are randomized to standard therapy versus bortezomib/standard combination therapy.
II. To determine the feasibility of combining bortezomib with standard chemotherapy in patients with de novo AML.
III. To compare the OS and EFS of high-risk patients treated with intensive Induction II with historical controls from AAML03P1 and AAML0531.
IV. To determine the feasibility of administering sorafenib (sorafenib tosylate) with standard chemotherapy and in a one year maintenance phase in patients with de novo high allelic ratio FLT3/ITD+ AML.
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
- — 至 29 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must be newly diagnosed with de novo acute myelogenous leukemia
- •Patients with previously untreated primary AML who meet the customary criteria for AML with >= 20% bone marrow blasts as set out in the 2008 World Health Organization (WHO) Myeloid Neoplasm Classification are eligible
- •Attempts to obtain bone marrow either by aspirate or biopsy must be made unless clinically prohibitive; in cases where it is clinically prohibitive, peripheral blood with an excess of 20% blasts and in which adequate flow cytometric and cytogenetics/fluorescent in situ hybridization (FISH) testing is feasible can be substituted for the marrow exam at diagnosis
- •Patients with < 20% bone marrow blasts are eligible if they have:
- •A karyotypic abnormality characteristic of de novo AML (t(8;21)(q22;q22), inv(16)(p13q22) or t(16;16)(p13;q22) or 11q23 abnormalities
- •The unequivocal presence of megakaryoblasts, or
- •Biopsy proven isolated myeloid sarcoma (myeloblastoma; chloroma, including leukemia cutis)
- •Patients with any performance status are eligible for enrollment
- •Prior therapy with hydroxyurea, all-trans retinoic acid (ATRA), corticosteroids (any route), and IT cytarabine given at diagnosis is allowed; hydroxyurea and ATRA must be discontinued prior to initiation of protocol therapy; patients who have previously received any other chemotherapy, radiation therapy or any other antileukemic therapy are not eligible for this protocol
排除标准
- •Patients with any of the following constitutional conditions are not eligible:
- •Fanconi anemia
- •Shwachman syndrome
- •Any other known bone marrow failure syndrome
- •Patients with constitutional trisomy 21 or with constitutional mosaicism of trisomy 21 Note: enrollment may occur pending results of clinically indicated studies to exclude these conditions
- •Patients with any of the following oncologic diagnoses are not eligible:
- •Any concurrent malignancy
- •Juvenile myelomonocytic leukemia (JMML)
- •Philadelphia chromosome positive AML
- •Biphenotypic or bilineal acute leukemia
- •Acute promyelocytic leukemia
- •Acute myeloid leukemia arising from myelodysplasia
- •Therapy-related myeloid neoplasms Note: enrollment may occur pending results of clinically indicated studies to exclude these conditions
- •Pregnancy and breast feeding
- •Female patients who are pregnant are ineligible
- •Lactating females are not eligible unless they have agreed not to breastfeed their infants
- •Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
- •Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation
研究组 & 干预措施
Arm B
See Detailed Description
干预措施: Quality-of-Life Assessment (Other)
Arm A
See Detailed Description
干预措施: Quality-of-Life Assessment (Other)
Arm A
See Detailed Description
干预措施: Asparaginase (Drug)
Arm A
See Detailed Description
干预措施: Cytarabine (Drug)
Arm A
See Detailed Description
干预措施: Etoposide (Drug)
Arm A
See Detailed Description
干预措施: Mitoxantrone Hydrochloride (Drug)
Arm A
See Detailed Description
干预措施: Pharmacological Study (Other)
Arm A
See Detailed Description
干预措施: Laboratory Biomarker Analysis (Other)
Arm B
See Detailed Description
干预措施: Laboratory Biomarker Analysis (Other)
Arm B
See Detailed Description
干预措施: Cytarabine (Drug)
Arm B
See Detailed Description
干预措施: Bortezomib (Drug)
Arm B
See Detailed Description
干预措施: Etoposide (Drug)
Arm C (Cohort 1)
See Detailed Description
干预措施: Daunorubicin Hydrochloride (Drug)
Arm C (Cohort 1)
See Detailed Description
干预措施: Cytarabine (Drug)
Arm C (Cohort 1)
See Detailed Description
干预措施: Asparaginase (Drug)
Arm C (Cohort 1)
See Detailed Description
干预措施: Mitoxantrone Hydrochloride (Drug)
Arm C (Cohort 1)
See Detailed Description
干预措施: Pharmacological Study (Other)
Arm C (Cohort 1)
See Detailed Description
干预措施: Laboratory Biomarker Analysis (Other)
Arm C (Cohort 1)
See Detailed Description
干预措施: Etoposide (Drug)
Arm C (Cohort 1)
See Detailed Description
干预措施: Questionnaire Administration (Other)
Arm C (Cohort 1)
See Detailed Description
干预措施: Quality-of-Life Assessment (Other)
Arm C (Cohort 1)
See Detailed Description
干预措施: Sorafenib Tosylate (Drug)
Arm C (Cohort 2)
See Detailed Description.
干预措施: Asparaginase (Drug)
Arm C (Cohort 2)
See Detailed Description.
干预措施: Cytarabine (Drug)
Arm C (Cohort 2)
See Detailed Description.
干预措施: Daunorubicin Hydrochloride (Drug)
Arm C (Cohort 2)
See Detailed Description.
干预措施: Laboratory Biomarker Analysis (Other)
Arm C (Cohort 2)
See Detailed Description.
干预措施: Etoposide (Drug)
Arm C (Cohort 2)
See Detailed Description.
干预措施: Quality-of-Life Assessment (Other)
Arm C (Cohort 3)
See Detailed Description. Different dose.
干预措施: Asparaginase (Drug)
Arm C (Cohort 3)
See Detailed Description. Different dose.
干预措施: Cytarabine (Drug)
Arm C (Cohort 3)
See Detailed Description. Different dose.
干预措施: Laboratory Biomarker Analysis (Other)
Arm C (Cohort 3)
See Detailed Description. Different dose.
干预措施: Mitoxantrone Hydrochloride (Drug)
Arm C (Cohort 3)
See Detailed Description. Different dose.
干预措施: Etoposide (Drug)
Arm D
See Detailed Description. May reassigned to Arm C.
干预措施: Laboratory Biomarker Analysis (Other)
Arm D
See Detailed Description. May reassigned to Arm C.
干预措施: Daunorubicin Hydrochloride (Drug)
Arm D
See Detailed Description. May reassigned to Arm C.
干预措施: Cytarabine (Drug)
Arm D
See Detailed Description. May reassigned to Arm C.
干预措施: Etoposide (Drug)
Arm C (Cohort 2)
See Detailed Description.
干预措施: Pharmacological Study (Other)
Arm C (Cohort 3)
See Detailed Description. Different dose.
干预措施: Quality-of-Life Assessment (Other)
Arm C (Cohort 3)
See Detailed Description. Different dose.
干预措施: Questionnaire Administration (Other)
Arm C (Cohort 3)
See Detailed Description. Different dose.
干预措施: Sorafenib Tosylate (Drug)
Arm C (Cohort 3)
See Detailed Description. Different dose.
干预措施: Pharmacological Study (Other)
Arm D
See Detailed Description. May reassigned to Arm C.
干预措施: Pharmacological Study (Other)
Arm D
See Detailed Description. May reassigned to Arm C.
干预措施: Quality-of-Life Assessment (Other)
Arm D
See Detailed Description. May reassigned to Arm C.
干预措施: Questionnaire Administration (Other)
Arm B
See Detailed Description
干预措施: Pharmacological Study (Other)
Arm A
See Detailed Description
干预措施: Questionnaire Administration (Other)
Arm B
See Detailed Description
干预措施: Questionnaire Administration (Other)
Arm C (Cohort 2)
See Detailed Description.
干预措施: Questionnaire Administration (Other)
Arm C (Cohort 2)
See Detailed Description.
干预措施: Mitoxantrone Hydrochloride (Drug)
Arm C (Cohort 3)
See Detailed Description. Different dose.
干预措施: Daunorubicin Hydrochloride (Drug)
Arm B
See Detailed Description
干预措施: Daunorubicin Hydrochloride (Drug)
Arm B
See Detailed Description
干预措施: Mitoxantrone Hydrochloride (Drug)
Arm C (Cohort 2)
See Detailed Description.
干预措施: Sorafenib Tosylate (Drug)
Arm A
See Detailed Description
干预措施: Daunorubicin Hydrochloride (Drug)
Arm B
See Detailed Description
干预措施: Asparaginase (Drug)
结局指标
主要结局
EFS for Patients on Arm C, Cohort 3
时间窗: Up to 3 years
The Kaplan-Meier method will be used to estimate 3-year EFS, defined as the time from study entry until induction failure, relapse, secondary malignancy, or death.
Event-free Survival (EFS) for Patients Without High Allelic Ratio FLT3/ITD+ Mutations
时间窗: Up to 3 years
The Kaplan-Meier method will be used to estimate 3-year EFS, defined as the time from study entry until induction failure, relapse, secondary malignancy, or death.
EFS for Patients on Arm C, Cohort 1
时间窗: Up to 3 years
The Kaplan-Meier method will be used to estimate 3-year EFS, defined as the time from study entry until induction failure, relapse, secondary malignancy, or death.
EFS for Patients on Arm C, Cohort 2
时间窗: Up to 3 years
The Kaplan-Meier method will be used to estimate 3-year EFS, defined as the time from study entry until induction failure, relapse, secondary malignancy, or death.
次要结局
- OS for Patients on Arm C, Cohort 1(Up to 3 years)
- Proportion of Patients Experiencing Grade 3 or Higher Non-hematologic Toxicities and Infections While on Protocol Therapy(Up to 2 years)
- Proportion of High Risk Children Without HR FLT3/ITD+ Converting From Positive MRD at End of Induction I to Negative MRD at the End of Induction II(Up to 8 weeks)
- Sorafenib Steady State Concentration(Up to 30 days)
- Change in Ejection Fraction(Up to 4 weeks)
- OS for Patients on Arm C, Cohort 3(Up to 3 years)
- Relapse Rate for Patients Without High Allelic Ratio FLT3/ITD+ Mutations(Up to 3 years)
- Overall Survival (OS) for Patients Without High Allelic Ratio FLT3/ITD+ Mutations(Up to 3 years)
- OS for Patients on Arm C, Cohort 2(Up to 3 years)
- Total Scale Score From Parent-reported Pediatric Quality of Life Inventory Module(Up to 14 days)
- Total Scale Score From Parent-reported Cancer Module(Up to 14 days)
- Bortezomib Clearance(Day 8 of Induction II)
- Serum Concentrations of GVHD Biomarker(Up to day 28 after SCT)
- Total Scale Score From Parent-reported Multidimensional Fatigue Scale Module(Up to 14 days)
- Change in Shortening Fraction(Up to 4 weeks)