A Phase 3 Randomized Trial for Patients With De Novo AML Comparing Standard Therapy Including Gemtuzumab Ozogamicin (GO) to CPX-351 With GO, and the Addition of the FLT3 Inhibitor Gilteritinib for Patients With FLT3 Mutations
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 1,400
- 试验地点
- 390
- 主要终点
- Event-free survival (EFS)
研究概览
简要总结
This phase III trial compares standard chemotherapy to therapy with liposome-encapsulated daunorubicin-cytarabine (CPX-351) and/or gilteritinib for patients with newly diagnosed acute myeloid leukemia with or without FLT3 mutations. Drugs used in chemotherapy, such as daunorubicin, cytarabine, and gemtuzumab ozogamicin, 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. CPX-351 is made up of daunorubicin and cytarabine and is made in a way that makes the drugs stay in the bone marrow longer and could be less likely to cause heart problems than traditional anthracycline drugs, a common class of chemotherapy drug. Some acute myeloid leukemia patients have an abnormality in the structure of a gene called FLT3. Genes are pieces of DNA (molecules that carry instructions for development, functioning, growth and reproduction) inside each cell that tell the cell what to do and when to grow and divide. FLT3 plays an important role in the normal making of blood cells. This gene can have permanent changes that cause it to function abnormally by making cancer cells grow. Gilteritinib may block the abnormal function of the FLT3 gene that makes cancer cells grow. The overall goals of this study are, 1) to compare the effects, good and/or bad, of CPX-351 with daunorubicin and cytarabine on people with newly diagnosed AML to find out which is better, 2) to study the effects, good and/or bad, of adding gilteritinib to AML therapy for patients with high amounts of FLT3/ITD or other FLT3 mutations and 3) to study changes in heart function during and after treatment for AML. Giving CPX-351 and/or gilteritinib with standard chemotherapy may work better in treating patients with acute myeloid leukemia compared to standard chemotherapy alone.
详细描述
PRIMARY OBJECTIVE:
I. To compare event-free survival (EFS) in children with de novo acute myeloid leukemia (AML) without FLT3 mutations who are randomly assigned to standard induction therapy on Arm A with daunorubicin, cytarabine (DA) and gemtuzumab ozogamicin (GO) (DA-GO) versus Arm B with CPX-351 and GO.
SECONDARY OBJECTIVES:
I. To compare overall survival (OS) and rates of end of Induction 1 (EOI1) minimal residual disease (MRD) in children with de novo AML without FLT3 mutations who are randomly assigned to standard induction therapy (Arm A) with DA-GO versus CPX-351 and GO (Arm B).
II. To estimate the EFS and rate of EOI1 MRD in FLT3 internal tandem duplication mutation positive patients (FLT3/ITD+; as defined by allelic ratio > 0.1) without favorable cytomolecular characteristics (NPM1 and/or CEBPA) receiving gilteritinib fumarate (gilteritinib) in combination with DA-GO (Arm AC).
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
- 6 Months 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All patients must be enrolled on APEC14B1 and consented to Eligibility Screening (Part A) prior to enrollment and treatment on AAML
- •Bone marrow and/or blood must have been submitted to the BPC via APEC14B1 for testing of FLT3 markers. Patients without samples submitted for FLT3 testing are not eligible
- •Patients must be at least 6 months of age and less than 22 years of age at the time of study enrollment
- •Patient must be newly diagnosed with de novo AML according to the 2016 World Health Organization (WHO) classification with or without extramedullary disease
- •Patient must have 1 of the following:
- •>= 20% bone marrow blasts (obtained within 14 days prior to enrollment)
- •In cases where extensive fibrosis may result in a dry tap, blast count can be obtained from touch imprints or estimated from an adequate bone marrow core biopsy
- •< 20% bone marrow blasts with one or more of the genetic abnormalities associated with childhood/young adult AML as provided in the protocol (sample obtained within 14 days prior to enrollment)
- •A complete blood count (CBC) documenting the presence of at least 1,000/uL (i.e., a white blood cell [WBC] count >= 10,000/uL with >= 10% blasts or a WBC count of >= 5,000/uL with >= 20% blasts) circulating leukemic cells (blasts) if a bone marrow aspirate or biopsy is pending or cannot be performed (performed within 7 days prior to enrollment)
- •ARM C: Patient must be >= 2 years of age at the time of Late Callback
- •ARM C: Patient must have FLT3/ITD allelic ratio > 0.1 as reported by Molecular Oncology
- •ARM C: Patient does not have any congenital long QT syndrome or congenital heart block
- •ARM C: Females of reproductive potential must agree to use effective contraception during treatment and for at least 6 months after the last dose of gilteritinib
- •ARM C: Lactating women must agree not to breastfeed during treatment with gilteritinib and for 2 months after the last dose of gilteritinib
- •ARM C: Males of reproductive potential must agree to use effective contraception during treatment and for at least 4 months after the last dose of gilteritinib
- •ARM D: Patient must be >= 2 years of age at the time of Late Callback
- •ARM D: Patient must have one of the clinically relevant non-ITD FLT3 activating mutations as reported by Foundation Medicine
- •ARM D: Females of reproductive potential must agree to use effective contraception during treatment and for at least 6 months after the last dose of gilteritinib
- •ARM D: Lactating women must agree not to breastfeed during treatment with gilteritinib and for 2 months after the last dose of gilteritinib
- •ARM D: Males of reproductive potential must agree to use effective contraception during treatment and for at least 4 months after the last dose of gilteritinib
- •NEUROPSYCHOLOGICAL TESTING: Patient must be enrolled on Arm A or Arm B. Patients who transfer to Arm C or Arm D are not eligible
- •NEUROPSYCHOLOGICAL TESTING: Patient must be 5 years or older at the time of enrollment
- •NEUROPSYCHOLOGICAL TESTING: English-, French- or Spanish-speaking
- •NEUROPSYCHOLOGICAL TESTING: No known history of neurodevelopmental disorder prior to diagnosis of AML (e.g., Down syndrome, fragile X, William syndrome, mental retardation)
- •NEUROPSYCHOLOGICAL TESTING: No significant visual or motor impairment that would prevent computer use or recognition of visual test stimuli
- •All patients and/or their parents or legal guardians must sign a written informed consent
- •All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
排除标准
- •Fanconi anemia
- •Shwachman Diamond syndrome
- •Patients with constitutional trisomy 21 or with constitutional mosaicism of trisomy 21
- •Telomere disorders
- •Germline predispositions known, or suspected by the treating physician to increase risk of toxicity with AML therapy
- •Any concurrent malignancy
- •Juvenile myelomonocytic leukemia (JMML)
- •Philadelphia chromosome positive AML
- •Mixed phenotype acute leukemia
- •Acute promyelocytic leukemia
- •Acute myeloid leukemia arising from myelodysplasia
- •Therapy-related myeloid neoplasms
- •Patients with persistent cardiac dysfunction prior to enrollment, defined as ejection fraction (EF) < 50% (preferred method Biplane Simpson's EF) or if EF unavailable, shortening fraction (SF) < 24%. *Note: if clinically safe and feasible, repeat echocardiogram is strongly advised in order to confirm cardiac dysfunction following clinical stabilization, particularly if occurring in the setting of sepsis or other transient physiologic stressor. If the repeat echocardiogram demonstrates an EF >= 50%, the patient is eligible to enroll and may receive an anthracycline-containing Induction regimen
- •Administration of prior anti-cancer therapy except as outlined below:
- •Hydroxyurea
- •All-trans retinoic acid (ATRA)
- •Corticosteroids (any route)
- •Intrathecal therapy given at diagnosis
- •In particular, strong inducers of CYP3A4 and/or P-glycoprotein (P-gp) should be avoided from the time of enrollment until it is determined whether the patient will receive gilteritinib. Patients receiving gilteritinib will be required to avoid strong CYP3A4 inducers and/or strong P-gp inducers for the duration of the study treatment
- •Patients < 8.3 kg at study enrollment are not eligible
- •Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
- •Lactating females who plan to breastfeed their infants
- •Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
- •ARM D: Patient does not have any congenital long QT syndrome or congenital heart block
研究组 & 干预措施
Arm A Low Risk Group 2
Arm A Low Risk Group 2: See Detailed Description.
干预措施: Bone Marrow Aspiration (Procedure)
Arm AC Low Risk Group 2
Arm AC Low Risk Group 2: See Detailed Description.
干预措施: Magnetic Resonance Imaging (Procedure)
Arm AC Low Risk Group 2
Arm AC Low Risk Group 2: See Detailed Description.
干预措施: Positron Emission Tomography (Procedure)
Arm AD Low Risk Group 2
Arm AD Low Risk Group 2: See Detailed Description.
干预措施: Biospecimen Collection (Procedure)
Arm BC Low Risk Group 2
Arm BC Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Liposome-encapsulated Daunorubicin-Cytarabine (Drug)
Arm B High Risk Group
Arm B High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Biospecimen Collection (Procedure)
Arm A High Risk Group
Arm A High Risk Group: See Detailed Description.
干预措施: Magnetic Resonance Imaging (Procedure)
Arm AC High Risk Group
Arm AC High Risk Group: See Detailed Description.
干预措施: Bone Marrow Biopsy (Procedure)
Arm AC High Risk Group
Arm AC High Risk Group: See Detailed Description.
干预措施: Questionnaire Administration (Other)
Arm AC Low Risk Group 2
Arm AC Low Risk Group 2: See Detailed Description.
干预措施: Biospecimen Collection (Procedure)
Arm AC High Risk Group
Arm AC High Risk Group: See Detailed Description.
干预措施: Bone Marrow Aspiration (Procedure)
Arm AC High Risk Group
Arm AC High Risk Group: See Detailed Description.
干预措施: Computed Tomography (Procedure)
Arm AC Low Risk Group 2
Arm AC Low Risk Group 2: See Detailed Description.
干预措施: Bone Marrow Aspiration (Procedure)
Arm AD High Risk Group
Arm AD High Risk Group: See Detailed Description.
干预措施: Allogeneic Hematopoietic Stem Cell Transplantation (Procedure)
Arm B High Risk Group
Arm B High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Positron Emission Tomography (Procedure)
Arm B High Risk Group
Arm B High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Questionnaire Administration (Other)
Arm B Low Risk Group 1
Arm B Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Biospecimen Collection (Procedure)
Arm B Low Risk Group 1
Arm B Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Positron Emission Tomography (Procedure)
Arm B Low Risk Group 2
Arm B Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Positron Emission Tomography (Procedure)
Arm AD High Risk Group
Arm AD High Risk Group: See Detailed Description.
干预措施: Magnetic Resonance Imaging (Procedure)
Arm AD Low Risk Group 2
Arm AD Low Risk Group 2: See Detailed Description.
干预措施: Questionnaire Administration (Other)
Arm B High Risk Group
Arm B High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Liposome-encapsulated Daunorubicin-Cytarabine (Drug)
Arm B High Risk Group
Arm B High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Magnetic Resonance Imaging (Procedure)
Arm B Low Risk Group 1
Arm B Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Liposome-encapsulated Daunorubicin-Cytarabine (Drug)
Arm B Low Risk Group 1
Arm B Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Questionnaire Administration (Other)
Arm BD Low Risk Group 2
Arm BD Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Biospecimen Collection (Procedure)
Arm BC Low Risk Group 2
Arm BC Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Methotrexate (Drug)
Arm BC Low Risk Group 2
Arm BC Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Etoposide (Drug)
Arm A Low Risk Group 1
Arm A Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Questionnaire Administration (Other)
Arm A Low Risk Group 1
Arm A Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Bone Marrow Aspiration (Procedure)
Arm A Low Risk Group 2
Arm A Low Risk Group 2: See Detailed Description.
干预措施: Biospecimen Collection (Procedure)
Arm A Low Risk Group 2
Arm A Low Risk Group 2: See Detailed Description.
干预措施: Magnetic Resonance Imaging (Procedure)
Arm A Low Risk Group 2
Arm A Low Risk Group 2: See Detailed Description.
干预措施: Positron Emission Tomography (Procedure)
Arm AC High Risk Group
Arm AC High Risk Group: See Detailed Description.
干预措施: Allogeneic Hematopoietic Stem Cell Transplantation (Procedure)
Arm B Low Risk Group 1
Arm B Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Bone Marrow Biopsy (Procedure)
Arm AD High Risk Group
Arm AD High Risk Group: See Detailed Description.
干预措施: Computed Tomography (Procedure)
Arm AD High Risk Group
Arm AD High Risk Group: See Detailed Description.
干预措施: Positron Emission Tomography (Procedure)
Arm B High Risk Group
Arm B High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Bone Marrow Biopsy (Procedure)
Arm B High Risk Group
Arm B High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Computed Tomography (Procedure)
Arm B Low Risk Group 1
Arm B Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Bone Marrow Aspiration (Procedure)
Arm B Low Risk Group 2
Arm B Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Biospecimen Collection (Procedure)
Arm B Low Risk Group 1
Arm B Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Computed Tomography (Procedure)
Arm B Low Risk Group 1
Arm B Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Magnetic Resonance Imaging (Procedure)
Arm B Low Risk Group 2
Arm B Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Bone Marrow Aspiration (Procedure)
Arm B Low Risk Group 2
Arm B Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Liposome-encapsulated Daunorubicin-Cytarabine (Drug)
Arm BC High Risk Group
Arm BC High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Bone Marrow Aspiration (Procedure)
Arm BC High Risk Group
Arm BC High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Bone Marrow Biopsy (Procedure)
Arm BC High Risk Group
Arm BC High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Computed Tomography (Procedure)
Arm BC High Risk Group
Arm BC High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Liposome-encapsulated Daunorubicin-Cytarabine (Drug)
Arm BC High Risk Group
Arm BC High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Magnetic Resonance Imaging (Procedure)
Arm BD Low Risk Group 2
Arm BD Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Liposome-encapsulated Daunorubicin-Cytarabine (Drug)
Arm AD High Risk Group
Arm AD High Risk Group: See Detailed Description.
干预措施: Therapeutic Hydrocortisone (Drug)
Arm A High Risk Group
Arm A High Risk Group: See Detailed Description.
干预措施: Fludeoxyglucose F-18 (Other)
Arm AC Low Risk Group 2
Arm AC Low Risk Group 2: See Detailed Description.
干预措施: Cytarabine (Drug)
Arm A Low Risk Group 2
Arm A Low Risk Group 2: See Detailed Description.
干预措施: Etoposide (Drug)
Arm AD Low Risk Group 2
Arm AD Low Risk Group 2: See Detailed Description.
干预措施: Therapeutic Hydrocortisone (Drug)
Arm B High Risk Group
Arm B High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Gemtuzumab Ozogamicin (Drug)
Arm BC Low Risk Group 2
Arm BC Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Therapeutic Hydrocortisone (Drug)
Arm BD Low Risk Group 2
Arm BD Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Dexrazoxane Hydrochloride (Drug)
Arm B Low Risk Group 1
Arm B Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Methotrexate (Drug)
Arm AD Low Risk Group 2
Arm AD Low Risk Group 2: See Detailed Description.
干预措施: Cytarabine (Drug)
Arm AD Low Risk Group 2
Arm AD Low Risk Group 2: See Detailed Description.
干预措施: Gemtuzumab Ozogamicin (Drug)
Arm AC Low Risk Group 2
Arm AC Low Risk Group 2: See Detailed Description.
干预措施: Etoposide (Drug)
Arm AC High Risk Group
Arm AC High Risk Group: See Detailed Description.
干预措施: Methotrexate (Drug)
Arm A Low Risk Group 2
Arm A Low Risk Group 2: See Detailed Description.
干预措施: Dexrazoxane Hydrochloride (Drug)
Arm AD Low Risk Group 2
Arm AD Low Risk Group 2: See Detailed Description.
干预措施: Etoposide (Drug)
Arm AC High Risk Group
Arm AC High Risk Group: See Detailed Description.
干预措施: Gilteritinib Fumarate (Drug)
Arm B Low Risk Group 2
Arm B Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Therapeutic Hydrocortisone (Drug)
Arm AC High Risk Group
Arm AC High Risk Group: See Detailed Description.
干预措施: Magnetic Resonance Imaging (Procedure)
Arm A High Risk Group
Arm A High Risk Group: See Detailed Description.
干预措施: Allogeneic Hematopoietic Stem Cell Transplantation (Procedure)
Arm A High Risk Group
Arm A High Risk Group: See Detailed Description.
干预措施: Daunorubicin Hydrochloride (Drug)
Arm A High Risk Group
Arm A High Risk Group: See Detailed Description.
干预措施: Cytarabine (Drug)
Arm A High Risk Group
Arm A High Risk Group: See Detailed Description.
干预措施: Biospecimen Collection (Procedure)
Arm A High Risk Group
Arm A High Risk Group: See Detailed Description.
干预措施: Bone Marrow Aspiration (Procedure)
Arm A High Risk Group
Arm A High Risk Group: See Detailed Description.
干预措施: Bone Marrow Biopsy (Procedure)
Arm A High Risk Group
Arm A High Risk Group: See Detailed Description.
干预措施: Computed Tomography (Procedure)
Arm A Low Risk Group 1
Arm A Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Asparaginase Erwinia chrysanthemi (Drug)
Arm AC Low Risk Group 2
Arm AC Low Risk Group 2: See Detailed Description.
干预措施: Bone Marrow Biopsy (Procedure)
Arm A Low Risk Group 1
Arm A Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Computed Tomography (Procedure)
Arm A Low Risk Group 2
Arm A Low Risk Group 2: See Detailed Description.
干预措施: Methotrexate (Drug)
Arm A Low Risk Group 1
Arm A Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Bone Marrow Biopsy (Procedure)
Arm BD Low Risk Group 2
Arm BD Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Positron Emission Tomography (Procedure)
Arm BD Low Risk Group 2
Arm BD Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Questionnaire Administration (Other)
Arm A Low Risk Group 2
Arm A Low Risk Group 2: See Detailed Description.
干预措施: Gemtuzumab Ozogamicin (Drug)
Arm AC High Risk Group
Arm AC High Risk Group: See Detailed Description.
干预措施: Dexrazoxane Hydrochloride (Drug)
Arm AC Low Risk Group 2
Arm AC Low Risk Group 2: See Detailed Description.
干预措施: Gemtuzumab Ozogamicin (Drug)
Arm AD Low Risk Group 2
Arm AD Low Risk Group 2: See Detailed Description.
干预措施: Daunorubicin Hydrochloride (Drug)
Arm AD Low Risk Group 2
Arm AD Low Risk Group 2: See Detailed Description.
干预措施: Fludeoxyglucose F-18 (Other)
Arm AD Low Risk Group 2
Arm AD Low Risk Group 2: See Detailed Description.
干预措施: Positron Emission Tomography (Procedure)
Arm B High Risk Group
Arm B High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Allogeneic Hematopoietic Stem Cell Transplantation (Procedure)
Arm B High Risk Group
Arm B High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Bone Marrow Aspiration (Procedure)
Arm B Low Risk Group 2
Arm B Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Questionnaire Administration (Other)
Arm BC High Risk Group
Arm BC High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Allogeneic Hematopoietic Stem Cell Transplantation (Procedure)
Arm BC High Risk Group
Arm BC High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Biospecimen Collection (Procedure)
Arm BC Low Risk Group 2
Arm BC Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Gilteritinib Fumarate (Drug)
Arm BD High Risk Group
Arm BD High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Methotrexate (Drug)
Arm AD High Risk Group
Arm AD High Risk Group: See Detailed Description.
干预措施: Questionnaire Administration (Other)
Arm AD Low Risk Group 2
Arm AD Low Risk Group 2: See Detailed Description.
干预措施: Bone Marrow Aspiration (Procedure)
Arm AD Low Risk Group 2
Arm AD Low Risk Group 2: See Detailed Description.
干预措施: Magnetic Resonance Imaging (Procedure)
Arm B Low Risk Group 2
Arm B Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Bone Marrow Biopsy (Procedure)
Arm A Low Risk Group 1
Arm A Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Magnetic Resonance Imaging (Procedure)
Arm A Low Risk Group 1
Arm A Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Positron Emission Tomography (Procedure)
Arm A Low Risk Group 2
Arm A Low Risk Group 2: See Detailed Description.
干预措施: Bone Marrow Biopsy (Procedure)
Arm AC High Risk Group
Arm AC High Risk Group: See Detailed Description.
干预措施: Biospecimen Collection (Procedure)
Arm AC High Risk Group
Arm AC High Risk Group: See Detailed Description.
干预措施: Positron Emission Tomography (Procedure)
Arm AC Low Risk Group 2
Arm AC Low Risk Group 2: See Detailed Description.
干预措施: Computed Tomography (Procedure)
Arm AC Low Risk Group 2
Arm AC Low Risk Group 2: See Detailed Description.
干预措施: Questionnaire Administration (Other)
Arm AD High Risk Group
Arm AD High Risk Group: See Detailed Description.
干预措施: Bone Marrow Aspiration (Procedure)
Arm AD High Risk Group
Arm AD High Risk Group: See Detailed Description.
干预措施: Bone Marrow Biopsy (Procedure)
Arm BC High Risk Group
Arm BC High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Positron Emission Tomography (Procedure)
Arm BC High Risk Group
Arm BC High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Questionnaire Administration (Other)
Arm BC Low Risk Group 2
Arm BC Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Biospecimen Collection (Procedure)
Arm BC Low Risk Group 2
Arm BC Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Bone Marrow Aspiration (Procedure)
Arm BC Low Risk Group 2
Arm BC Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Bone Marrow Biopsy (Procedure)
Arm BC Low Risk Group 2
Arm BC Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Computed Tomography (Procedure)
Arm BC Low Risk Group 2
Arm BC Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Magnetic Resonance Imaging (Procedure)
Arm BC Low Risk Group 2
Arm BC Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Positron Emission Tomography (Procedure)
Arm BC Low Risk Group 2
Arm BC Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Questionnaire Administration (Other)
Arm BD High Risk Group
Arm BD High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Allogeneic Hematopoietic Stem Cell Transplantation (Procedure)
Arm BD Low Risk Group 2
Arm BD Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Bone Marrow Aspiration (Procedure)
Arm BD Low Risk Group 2
Arm BD Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Bone Marrow Biopsy (Procedure)
Arm BD Low Risk Group 2
Arm BD Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Computed Tomography (Procedure)
Arm A Low Risk Group 1
Arm A Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Fludeoxyglucose F-18 (Other)
Arm A Low Risk Group 2
Arm A Low Risk Group 2: See Detailed Description.
干预措施: Therapeutic Hydrocortisone (Drug)
Arm AC Low Risk Group 2
Arm AC Low Risk Group 2: See Detailed Description.
干预措施: Gilteritinib Fumarate (Drug)
Arm AC Low Risk Group 2
Arm AC Low Risk Group 2: See Detailed Description.
干预措施: Methotrexate (Drug)
Arm AC Low Risk Group 2
Arm AC Low Risk Group 2: See Detailed Description.
干预措施: Mitoxantrone Hydrochloride (Drug)
Arm AD Low Risk Group 2
Arm AD Low Risk Group 2: See Detailed Description.
干预措施: Mitoxantrone Hydrochloride (Drug)
Arm B Low Risk Group 2
Arm B Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Methotrexate (Drug)
Arm AD High Risk Group
Arm AD High Risk Group: See Detailed Description.
干预措施: Etoposide (Drug)
Arm B High Risk Group
Arm B High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Fludeoxyglucose F-18 (Other)
Arm AC High Risk Group
Arm AC High Risk Group: See Detailed Description.
干预措施: Fludeoxyglucose F-18 (Other)
Arm A Low Risk Group 1
Arm A Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Methotrexate (Drug)
Arm AD High Risk Group
Arm AD High Risk Group: See Detailed Description.
干预措施: Daunorubicin Hydrochloride (Drug)
Arm AC High Risk Group
Arm AC High Risk Group: See Detailed Description.
干预措施: Etoposide (Drug)
Arm AD High Risk Group
Arm AD High Risk Group: See Detailed Description.
干预措施: Fludeoxyglucose F-18 (Other)
Arm B Low Risk Group 1
Arm B Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Etoposide (Drug)
Arm AD Low Risk Group 2
Arm AD Low Risk Group 2: See Detailed Description.
干预措施: Dexrazoxane Hydrochloride (Drug)
Arm B Low Risk Group 1
Arm B Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Asparaginase Erwinia chrysanthemi (Drug)
Arm B Low Risk Group 2
Arm B Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Asparaginase Erwinia chrysanthemi (Drug)
Arm AD Low Risk Group 2
Arm AD Low Risk Group 2: See Detailed Description.
干预措施: Gilteritinib Fumarate (Drug)
Arm B Low Risk Group 1
Arm B Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Cytarabine (Drug)
Arm B Low Risk Group 2
Arm B Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Mitoxantrone Hydrochloride (Drug)
Arm BD High Risk Group
Arm BD High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Cytarabine (Drug)
Arm BC Low Risk Group 2
Arm BC Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Mitoxantrone Hydrochloride (Drug)
Arm B High Risk Group
Arm B High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Cytarabine (Drug)
Arm AD High Risk Group
Arm AD High Risk Group: See Detailed Description.
干预措施: Gemtuzumab Ozogamicin (Drug)
Arm BD High Risk Group
Arm BD High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Etoposide (Drug)
Arm BD Low Risk Group 2
Arm BD Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Gilteritinib Fumarate (Drug)
Arm BD High Risk Group
Arm BD High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Gemtuzumab Ozogamicin (Drug)
Arm BD Low Risk Group 2
Arm BD Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Cytarabine (Drug)
Arm BD Low Risk Group 2
Arm BD Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Asparaginase Erwinia chrysanthemi (Drug)
Arm A High Risk Group
Arm A High Risk Group: See Detailed Description.
干预措施: Questionnaire Administration (Other)
Arm A Low Risk Group 1
Arm A Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Biospecimen Collection (Procedure)
Arm A High Risk Group
Arm A High Risk Group: See Detailed Description.
干预措施: Positron Emission Tomography (Procedure)
Arm AD Low Risk Group 2
Arm AD Low Risk Group 2: See Detailed Description.
干预措施: Bone Marrow Biopsy (Procedure)
Arm B Low Risk Group 1
Arm B Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Fludeoxyglucose F-18 (Other)
Arm BC High Risk Group
Arm BC High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Gilteritinib Fumarate (Drug)
Arm BC High Risk Group
Arm BC High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Etoposide (Drug)
Arm BC High Risk Group
Arm BC High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Fludeoxyglucose F-18 (Other)
Arm A High Risk Group
Arm A High Risk Group: See Detailed Description.
干预措施: Methotrexate (Drug)
Arm A High Risk Group
Arm A High Risk Group: See Detailed Description.
干预措施: Gemtuzumab Ozogamicin (Drug)
Arm BD High Risk Group
Arm BD High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Therapeutic Hydrocortisone (Drug)
Arm A Low Risk Group 2
Arm A Low Risk Group 2: See Detailed Description.
干预措施: Asparaginase Erwinia chrysanthemi (Drug)
Arm A Low Risk Group 2
Arm A Low Risk Group 2: See Detailed Description.
干预措施: Fludeoxyglucose F-18 (Other)
Arm AC Low Risk Group 2
Arm AC Low Risk Group 2: See Detailed Description.
干预措施: Dexrazoxane Hydrochloride (Drug)
Arm A Low Risk Group 1
Arm A Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Dexrazoxane Hydrochloride (Drug)
Arm A Low Risk Group 1
Arm A Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Etoposide (Drug)
Arm A Low Risk Group 1
Arm A Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Gemtuzumab Ozogamicin (Drug)
Arm AC Low Risk Group 2
Arm AC Low Risk Group 2: See Detailed Description.
干预措施: Fludeoxyglucose F-18 (Other)
Arm A High Risk Group
Arm A High Risk Group: See Detailed Description.
干预措施: Therapeutic Hydrocortisone (Drug)
Arm B High Risk Group
Arm B High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Therapeutic Hydrocortisone (Drug)
Arm B Low Risk Group 2
Arm B Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Cytarabine (Drug)
Arm AD High Risk Group
Arm AD High Risk Group: See Detailed Description.
干预措施: Methotrexate (Drug)
Arm B Low Risk Group 1
Arm B Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Gemtuzumab Ozogamicin (Drug)
Arm B Low Risk Group 1
Arm B Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Therapeutic Hydrocortisone (Drug)
Arm B High Risk Group
Arm B High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Methotrexate (Drug)
Arm AD Low Risk Group 2
Arm AD Low Risk Group 2: See Detailed Description.
干预措施: Methotrexate (Drug)
Arm B High Risk Group
Arm B High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Etoposide (Drug)
Arm B Low Risk Group 2
Arm B Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Etoposide (Drug)
Arm BD Low Risk Group 2
Arm BD Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Etoposide (Drug)
Arm BC High Risk Group
Arm BC High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Therapeutic Hydrocortisone (Drug)
Arm BC Low Risk Group 2
Arm BC Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Fludeoxyglucose F-18 (Other)
Arm BC Low Risk Group 2
Arm BC Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Dexrazoxane Hydrochloride (Drug)
Arm BC High Risk Group
Arm BC High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Cytarabine (Drug)
Arm AD High Risk Group
Arm AD High Risk Group: See Detailed Description.
干预措施: Cytarabine (Drug)
Arm BD Low Risk Group 2
Arm BD Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Gemtuzumab Ozogamicin (Drug)
Arm BD Low Risk Group 2
Arm BD Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Methotrexate (Drug)
Arm AC Low Risk Group 2
Arm AC Low Risk Group 2: See Detailed Description.
干预措施: Therapeutic Hydrocortisone (Drug)
Arm A Low Risk Group 2
Arm A Low Risk Group 2: See Detailed Description.
干预措施: Cytarabine (Drug)
Arm A Low Risk Group 1
Arm A Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Cytarabine (Drug)
Arm AC High Risk Group
Arm AC High Risk Group: See Detailed Description.
干预措施: Therapeutic Hydrocortisone (Drug)
Arm AD High Risk Group
Arm AD High Risk Group: See Detailed Description.
干预措施: Gilteritinib Fumarate (Drug)
Arm AC High Risk Group
Arm AC High Risk Group: See Detailed Description.
干预措施: Daunorubicin Hydrochloride (Drug)
Arm A High Risk Group
Arm A High Risk Group: See Detailed Description.
干预措施: Etoposide (Drug)
Arm B Low Risk Group 2
Arm B Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Fludeoxyglucose F-18 (Other)
Arm A High Risk Group
Arm A High Risk Group: See Detailed Description.
干预措施: Dexrazoxane Hydrochloride (Drug)
Arm AC High Risk Group
Arm AC High Risk Group: See Detailed Description.
干预措施: Gemtuzumab Ozogamicin (Drug)
Arm BC High Risk Group
Arm BC High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Gemtuzumab Ozogamicin (Drug)
Arm AC High Risk Group
Arm AC High Risk Group: See Detailed Description.
干预措施: Cytarabine (Drug)
Arm A Low Risk Group 1
Arm A Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Therapeutic Hydrocortisone (Drug)
Arm B Low Risk Group 2
Arm B Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Gemtuzumab Ozogamicin (Drug)
Arm AD High Risk Group
Arm AD High Risk Group: See Detailed Description.
干预措施: Dexrazoxane Hydrochloride (Drug)
Arm BC Low Risk Group 2
Arm BC Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Gemtuzumab Ozogamicin (Drug)
Arm BC Low Risk Group 2
Arm BC Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Cytarabine (Drug)
Arm AD High Risk Group
Arm AD High Risk Group: See Detailed Description.
干预措施: Biospecimen Collection (Procedure)
Arm AD Low Risk Group 2
Arm AD Low Risk Group 2: See Detailed Description.
干预措施: Computed Tomography (Procedure)
Arm A Low Risk Group 2
Arm A Low Risk Group 2: See Detailed Description.
干预措施: Mitoxantrone Hydrochloride (Drug)
Arm BC High Risk Group
Arm BC High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Methotrexate (Drug)
Arm AD Low Risk Group 2
Arm AD Low Risk Group 2: See Detailed Description.
干预措施: Asparaginase Erwinia chrysanthemi (Drug)
Arm A Low Risk Group 2
Arm A Low Risk Group 2: See Detailed Description.
干预措施: Daunorubicin Hydrochloride (Drug)
Arm BD High Risk Group
Arm BD High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Fludeoxyglucose F-18 (Other)
Arm A Low Risk Group 2
Arm A Low Risk Group 2: See Detailed Description.
干预措施: Questionnaire Administration (Other)
Arm B Low Risk Group 2
Arm B Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Computed Tomography (Procedure)
Arm BD High Risk Group
Arm BD High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Positron Emission Tomography (Procedure)
Arm AC Low Risk Group 2
Arm AC Low Risk Group 2: See Detailed Description.
干预措施: Daunorubicin Hydrochloride (Drug)
Arm A Low Risk Group 2
Arm A Low Risk Group 2: See Detailed Description.
干预措施: Computed Tomography (Procedure)
Arm BD High Risk Group
Arm BD High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Biospecimen Collection (Procedure)
Arm BD High Risk Group
Arm BD High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Bone Marrow Aspiration (Procedure)
Arm BD High Risk Group
Arm BD High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Bone Marrow Biopsy (Procedure)
Arm BD High Risk Group
Arm BD High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Questionnaire Administration (Other)
Arm BD High Risk Group
Arm BD High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Computed Tomography (Procedure)
Arm BD High Risk Group
Arm BD High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Liposome-encapsulated Daunorubicin-Cytarabine (Drug)
Arm BD High Risk Group
Arm BD High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Magnetic Resonance Imaging (Procedure)
Arm BD Low Risk Group 2
Arm BD Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Magnetic Resonance Imaging (Procedure)
Arm BD Low Risk Group 2
Arm BD Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Fludeoxyglucose F-18 (Other)
Arm AC Low Risk Group 2
Arm AC Low Risk Group 2: See Detailed Description.
干预措施: Asparaginase Erwinia chrysanthemi (Drug)
Arm A Low Risk Group 1
Arm A Low Risk Group 1: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Daunorubicin Hydrochloride (Drug)
Arm BC Low Risk Group 2
Arm BC Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Asparaginase Erwinia chrysanthemi (Drug)
Arm BD Low Risk Group 2
Arm BD Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Therapeutic Hydrocortisone (Drug)
Arm BD High Risk Group
Arm BD High Risk Group: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Gilteritinib Fumarate (Drug)
Arm BD Low Risk Group 2
Arm BD Low Risk Group 2: See Detailed Description. (CLOSED TO ACCRUAL 11/19/2024)
干预措施: Mitoxantrone Hydrochloride (Drug)
结局指标
主要结局
Event-free survival (EFS)
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, or death.
次要结局
- Overall survival (OS)(Up to 3 years)
- Proportion of patients positive for minimal residual disease (MRD+)(Up to 4 weeks)
- Proportion of patients who died during protocol therapy(Up to 2 years)
- Incidence of adverse events(Up to 2 years)
- Relapse rate(Up to 3 years)
- Treatment-related mortality rate (TRM)(Up to 3 years)
- Number of patients who undergo hematopoietic stem cell transplant (HSCT)(Up to 3 years)