A Phase II Trial of Epigenetic Priming in Patients With Newly Diagnosed Acute Myeloid Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 206
- 试验地点
- 16
- 主要终点
- Proportion of evaluable patients who tolerate five days of single agent DMTi before a standard chemotherapy combination
研究概览
简要总结
The overall aim of this study is to determine if epigenetic priming with a DNA methyltransferase inhibitor (DMTi) prior to chemotherapy blocks is tolerable and carries evidence of a clinical efficacy signal as determined by minimal residual disease (MRD), event-free survival (EFS), and overall survival (OS). Tolerability for each of the agents, as well as total reduction in DNA methylation and outcome assessments will be done to simultaneously obtain preliminary biological and clinical data for each DMTi in parallel.
PRIMARY OBJECTIVES:
- Evaluate the tolerability of five days of epigenetic priming with azacitidine and decitabine as a single agent DMTi prior to standard AML chemotherapy blocks.
- Evaluate the change in genome-wide methylation burden induced by five days of epigenetic priming and the association of post-priming genome-wide methylation burden with event-free survival among pediatric AML patients.
SECONDARY OBJECTIVES
- Describe minimal residual disease levels following Induction I chemotherapy in patients that receive DMTi.
- Estimate the event-free survival and overall survival of patients receiving a DMTi prior to chemotherapy courses.
详细描述
To determine tolerability, priming with DMTi (azacitidine or decitabine) will be limited to Induction I and II during Part 1 of the study. If DMTi treatment is tolerated during Part 1, the investigators will go on to an Expansion Phase (Part 2) that includes DMTi priming prior to all chemotherapy blocks.
Treatment will consist of 5 blocks of conventional chemotherapy: Induction I, Induction II, Intensification I, Intensification II, and Intensification III over approximately 5 months.
RANDOMIZATION: Patients will be randomized to receive one of two DMTi (azacitidine or decitabine) for 5 days prior to Induction I. Intrathecal (ITHMA) treatments will be given right before treatment on this study or on Day 1 of Induction I treatment. Leucovorin will be given 24-30 hours following ITHMA.
INDUCTION I CHEMOTHERAPY: Patients receive cytarabine, daunorubicin, and etoposide.
INDUCTION II CHEMOTHERAPY; Patients receive their assigned DMTi for 5 days followed by fludarabine, cytarabine, G-CSF, and idarubicin.
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
- 29 Days 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnostic criteria: Patients must have one of the following diagnoses:
- •Acute myeloid leukemia fulfilling the criteria of the WHO Classification (see Appendix I), or
- •>5% but < 20% marrow myeloblasts and evidence of a clonal de novo AML genetic abnormality [e.g., t(8;21), inv(16), t(9;11)], or
- •Myeloid sarcoma (also referred to as extramedullary myeloid tumor, granulocytic sarcoma, or chloroma), with or without evidence of a leukemia process in the bone marrow or peripheral blood, with confirmation of myeloid differentiation, or
- •High grade myelodysplastic syndrome (MDS) with greater than 5% blasts, or
- •Patients with treatment related myeloid neoplasms including AML and MDS, provided their cumulative anthracycline dose has not exceeded 230 mg/m2 doxorubicin equivalents.
- •Other criteria - Patients must meet all the following criteria:
- •Age > 28 days and < 22 years at time of study entry inclusive, and
- •No prior therapy for this malignancy except for one dose of intrathecal therapy and the use of hydroxyurea or low-dose cytarabine (100-200 mg/m2 per day for one week or less for hyperleukocytosis), and
- •Written informed consent according to institutional guidelines, and
- •Female patients of childbearing potential must have a negative pregnancy test within 2 weeks prior to enrollment, and
- •Male and female participants of reproductive potential must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment.
排除标准
- •Down syndrome
- •Acute promyelocytic leukemia (APL)
- •BCR-ABL1 chronic myeloid leukemia in blast crisis (CML-BC)
- •Juvenile myelomonocytic leukemia (JMML)
- •Fanconi anemia (FA)
- •Kostmann syndrome
- •Shwachman syndrome
- •Other bone marrow failure syndromes or low grade (<5% bone marrow blasts) MDS.
- •Use of concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol.
- •Use of investigational agents within 30 days or any anticancer therapy for this malignancy within 2 weeks before study entry with the exception of IT therapy, hydroxyurea, or low-dose cytarabine as specified in the protocol document. The patient must have recovered from all acute toxicities from any previous therapy.
- •Systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).
- •Pregnant or lactating.
- •Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.
- •Prior chemotherapy, with the exception of hydroxyurea or low-dose cytarabine as specified in the protocol document. The patient must have recovered from all acute toxicities from any previous therapy.
- •Patients with treatment related myeloid neoplasms with cumulative anthracyclines greater than 230 mg/m2 doxorubicin equivalents.
研究组 & 干预措施
AZA+ADE | AZA+FLAG+Ida+Sor | AZA+AE+Sor | AZA+MA+Sor
Part 2 Dose Expansion with AZA - Low Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and low- risk Intensifications I & II. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, ITMHA.
干预措施: Dexrazoxane (Drug)
DAC+ADE | DAC+FLAG+Ida+Sor | DAC+AE+Sor|DAC+MA+Sor
Part 2 Dose Expansion with DAC - Low Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and low-risk Intensifications I & II. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, ITMHA.
干预措施: Decitabine (Drug)
DAC+ADE | DAC+FLAG+Ida+Sor | DAC+AE+Sor|DAC+MA+Sor
Part 2 Dose Expansion with DAC - Low Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and low-risk Intensifications I & II. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, ITMHA.
干预措施: Cytarabine (Drug)
DAC+ADE | DAC+FLAG+Ida+Sor | DAC+AE+Sor|DAC+MA+Sor
Part 2 Dose Expansion with DAC - Low Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and low-risk Intensifications I & II. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, ITMHA.
干预措施: ITMHA (Combination Product)
DAC+ADE | DAC+FLAG+Ida+Sor | DAC+AE+Sor|DAC+MA+Sor
Part 2 Dose Expansion with DAC - Low Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and low-risk Intensifications I & II. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, ITMHA.
干预措施: Idarubicin (Drug)
DAC+ADE | DAC+FLAG+Ida+Sor | DAC+AE+Sor|DAC+MA+Sor
Part 2 Dose Expansion with DAC - Low Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and low-risk Intensifications I & II. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, ITMHA.
干预措施: Mitoxantrone (Drug)
DAC|+ADE | +FLAG+Ida+Sor | +AE+Sor | +MA+Sor | +Asp+AraC+Sor
Part 2 Dose Expansion with DAC - Intermediate-Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and intermediate-risk Intensifications I, II and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: Daunorubicin (Drug)
DAC|+ADE | +FLAG+Ida+Sor | +AE+Sor | +MA+Sor | +Asp+AraC+Sor
Part 2 Dose Expansion with DAC - Intermediate-Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and intermediate-risk Intensifications I, II and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: Asparaginase Erwinia Chrysanthemi, Recombinant-Rywn (Drug)
DAC|+ADE | +FLAG+Ida+Sor | +AE+Sor | +MA+Sor | +Asp+AraC+Sor
Part 2 Dose Expansion with DAC - Intermediate-Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and intermediate-risk Intensifications I, II and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: Dexrazoxane (Drug)
AZA+ADE | AZA+FLAG-Ida+Sor | AE | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with AZA - High Risk (no donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Induction I & II and high-risk intensifications I, II & III without azacitidine. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, ITMHA.
干预措施: Azacitidine (Drug)
AZA+ADE | AZA+FLAG-Ida+Sor | AE | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with AZA - High Risk (no donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Induction I & II and high-risk intensifications I, II & III without azacitidine. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, ITMHA.
干预措施: Cytarabine (Drug)
AZA+ADE | AZA+FLAG-Ida+Sor | AE | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with AZA - High Risk (no donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Induction I & II and high-risk intensifications I, II & III without azacitidine. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, ITMHA.
干预措施: Daunorubicin (Drug)
AZA+ADE | AZA+FLAG-Ida+Sor | AE | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with AZA - High Risk (no donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Induction I & II and high-risk intensifications I, II & III without azacitidine. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, ITMHA.
干预措施: ITMHA (Combination Product)
AZA+ADE | AZA+FLAG-Ida+Sor | AE | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with AZA - High Risk (no donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Induction I & II and high-risk intensifications I, II & III without azacitidine. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, ITMHA.
干预措施: Etoposide (Drug)
AZA+ADE | AZA+FLAG-Ida+Sor | AE | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with AZA - High Risk (no donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Induction I & II and high-risk intensifications I, II & III without azacitidine. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, ITMHA.
干预措施: Fludarabine (Drug)
AZA+ADE | AZA+FLAG-Ida+Sor | AE | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with AZA - High Risk (no donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Induction I & II and high-risk intensifications I, II & III without azacitidine. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, ITMHA.
干预措施: Erwinia asparaginase (Drug)
AZA+ADE | AZA+FLAG-Ida+Sor | AE | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with AZA - High Risk (no donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Induction I & II and high-risk intensifications I, II & III without azacitidine. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, ITMHA.
干预措施: Sorafenib (Drug)
AZA | + ADE | +FLAG+Ida+Sor| +AE+Sor | +MA+Sor | +Asp+AraC+Sor
Part 2 Dose Expansion with AZA - High Risk (no donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and high-risk Intensifications I, II and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: Erwinia asparaginase (Drug)
DAC |+ADE |+FLAG+Ida+Sor |+AE+Sor|+MA+Sor|+Asp+AraC+Sor
Part 2 Dose Expansion with DAC - High Risk (no donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and high-risk Intensifications I, II and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: Decitabine (Drug)
DAC+ADE | DAC+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with DAC - High Risk (with donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive high-risk Intensifications I or high risk intensification III without decitabine. Patients will proceed to stem cell transplant. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant
干预措施: Sorafenib (Drug)
DAC+ADE | DAC+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with DAC - High Risk (with donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive high-risk Intensifications I or high risk intensification III without decitabine. Patients will proceed to stem cell transplant. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant
干预措施: G-CSF (Drug)
DAC+ADE | DAC+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with DAC - High Risk (with donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive high-risk Intensifications I or high risk intensification III without decitabine. Patients will proceed to stem cell transplant. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant
干预措施: Stem Cell Transplant (Biological)
DAC+ADE | DAC+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with DAC - High Risk (with donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive high-risk Intensifications I or high risk intensification III without decitabine. Patients will proceed to stem cell transplant. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant
干预措施: Dexrazoxane (Drug)
DAC |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor
Part 2 Dose Expansion with DAC - High Risk (with donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and high-risk Intensifications I or high risk intensification III. Patients will proceed to stem cell transplant. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant
干预措施: Decitabine (Drug)
DAC |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor
Part 2 Dose Expansion with DAC - High Risk (with donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and high-risk Intensifications I or high risk intensification III. Patients will proceed to stem cell transplant. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant
干预措施: Cytarabine (Drug)
DAC |+ADE |+FLAG+Ida+Sor |+AE+Sor|+MA+Sor|+Asp+AraC+Sor
Part 2 Dose Expansion with DAC - High Risk (no donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and high-risk Intensifications I, II and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: Fludarabine (Drug)
AZA+ADE | AZA+FLAG+Ida | AE | MA
Part 1 Tolerability with AZA - Low Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and then receive low-risk intensifications I & II without azacitidine.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide,dexrazoxane, fludarabine, idarubicin, G-CSF, mitoxantrone., ITMHA.
干预措施: ITMHA (Combination Product)
DAC+ADE | DAC+FLAG+Ida | AE | MA
Part 1 Tolerability with DAC - Low Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive low-risk Intensifications I & II without decitabine.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, ITMHA.
干预措施: ITMHA (Combination Product)
AZA+ADE | AZA+FLAG+Ida | AE | MA | Asp+AraC
Part 1 Tolerability with AZA - Intermediate Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and then receive intermediate risk Intensifications I, II & III without azacitidine.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, erwinia asparaginase, ITMHA,
干预措施: ITMHA (Combination Product)
DAC+ADE | DAC+FLAG+Ida | AE | MA | Asp+AraC
Part 1 Tolerability with DAC - Intermediate Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive intermediate-risk Intensifications I, II & III without decitabine.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, erwinia asparaginase, ITMHA.
干预措施: ITMHA (Combination Product)
AZA| +ADE | +FLAG+Ida+Sor| +AE+Sor| +MA+Sor| +Asp+AraC+Sor
Part 2 Dose Expansion with AZA - Intermediate-Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and intermediate-risk Intensification I, II, and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: ITMHA (Combination Product)
AZA| +ADE | +FLAG+Ida+Sor| +AE+Sor| +MA+Sor| +Asp+AraC+Sor
Part 2 Dose Expansion with AZA - Intermediate-Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and intermediate-risk Intensification I, II, and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: Cytarabine (Drug)
DAC |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor
Part 2 Dose Expansion with DAC - High Risk (with donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and high-risk Intensifications I or high risk intensification III. Patients will proceed to stem cell transplant. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant
干预措施: Idarubicin (Drug)
DAC|+ADE | +FLAG+Ida+Sor | +AE+Sor | +MA+Sor | +Asp+AraC+Sor
Part 2 Dose Expansion with DAC - Intermediate-Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and intermediate-risk Intensifications I, II and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: ITMHA (Combination Product)
DAC |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor
Part 2 Dose Expansion with DAC - High Risk (with donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and high-risk Intensifications I or high risk intensification III. Patients will proceed to stem cell transplant. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant
干预措施: G-CSF (Drug)
DAC+ADE | DAC+FLAG+Ida+Sor | AE | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with DAC - High Risk (no donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive high-risk Intensifications I, II & III without decitabine. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, ITMHA.
干预措施: ITMHA (Combination Product)
AZA | + ADE | +FLAG+Ida+Sor| +AE+Sor | +MA+Sor | +Asp+AraC+Sor
Part 2 Dose Expansion with AZA - High Risk (no donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and high-risk Intensifications I, II and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: ITMHA (Combination Product)
DAC |+ADE |+FLAG+Ida+Sor |+AE+Sor|+MA+Sor|+Asp+AraC+Sor
Part 2 Dose Expansion with DAC - High Risk (no donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and high-risk Intensifications I, II and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: ITMHA (Combination Product)
AZA+ADE | AZA+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with AZA- High Risk (with donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Induction I Induction II and high-risk Intensifications I or high risk intensification III without azacitidine. Patients will proceed to stem cell transplant. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: azacitidine cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant.
干预措施: ITMHA (Combination Product)
AZA+ADE | AZA+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with AZA- High Risk (with donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Induction I Induction II and high-risk Intensifications I or high risk intensification III without azacitidine. Patients will proceed to stem cell transplant. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: azacitidine cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant.
干预措施: Stem Cell Transplant (Biological)
DAC+ADE | DAC+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with DAC - High Risk (with donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive high-risk Intensifications I or high risk intensification III without decitabine. Patients will proceed to stem cell transplant. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant
干预措施: ITMHA (Combination Product)
DAC |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor
Part 2 Dose Expansion with DAC - High Risk (with donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and high-risk Intensifications I or high risk intensification III. Patients will proceed to stem cell transplant. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant
干预措施: ITMHA (Combination Product)
DAC |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor
Part 2 Dose Expansion with DAC - High Risk (with donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and high-risk Intensifications I or high risk intensification III. Patients will proceed to stem cell transplant. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant
干预措施: Stem Cell Transplant (Biological)
AZA |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor
Part 2 Dose Expansion with AZA - High Risk (with donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and high-risk Intensification I or high risk intensification III. Patients will proceed to stem cell transplant. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G-CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant.
干预措施: ITMHA (Combination Product)
AZA |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor
Part 2 Dose Expansion with AZA - High Risk (with donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and high-risk Intensification I or high risk intensification III. Patients will proceed to stem cell transplant. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G-CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant.
干预措施: G-CSF (Drug)
AZA |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor
Part 2 Dose Expansion with AZA - High Risk (with donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and high-risk Intensification I or high risk intensification III. Patients will proceed to stem cell transplant. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G-CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant.
干预措施: Stem Cell Transplant (Biological)
AZA |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor
Part 2 Dose Expansion with AZA - High Risk (with donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and high-risk Intensification I or high risk intensification III. Patients will proceed to stem cell transplant. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G-CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant.
干预措施: Azacitidine (Drug)
DAC |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor
Part 2 Dose Expansion with DAC - High Risk (with donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and high-risk Intensifications I or high risk intensification III. Patients will proceed to stem cell transplant. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant
干预措施: Erwinia asparaginase (Drug)
DAC |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor
Part 2 Dose Expansion with DAC - High Risk (with donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and high-risk Intensifications I or high risk intensification III. Patients will proceed to stem cell transplant. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant
干预措施: Fludarabine (Drug)
DAC |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor
Part 2 Dose Expansion with DAC - High Risk (with donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and high-risk Intensifications I or high risk intensification III. Patients will proceed to stem cell transplant. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant
干预措施: Sorafenib (Drug)
AZA| +ADE | +FLAG+Ida+Sor| +AE+Sor| +MA+Sor| +Asp+AraC+Sor
Part 2 Dose Expansion with AZA - Intermediate-Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and intermediate-risk Intensification I, II, and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: Azacitidine (Drug)
AZA+ADE | AZA+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with AZA- High Risk (with donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Induction I Induction II and high-risk Intensifications I or high risk intensification III without azacitidine. Patients will proceed to stem cell transplant. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: azacitidine cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant.
干预措施: Azacitidine (Drug)
AZA+ADE | AZA+FLAG+Ida+Sor | AZA+AE+Sor | AZA+MA+Sor
Part 2 Dose Expansion with AZA - Low Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and low- risk Intensifications I & II. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, ITMHA.
干预措施: ITMHA (Combination Product)
AZA+ADE | AZA+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with AZA- High Risk (with donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Induction I Induction II and high-risk Intensifications I or high risk intensification III without azacitidine. Patients will proceed to stem cell transplant. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: azacitidine cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant.
干预措施: Daunorubicin (Drug)
AZA| +ADE | +FLAG+Ida+Sor| +AE+Sor| +MA+Sor| +Asp+AraC+Sor
Part 2 Dose Expansion with AZA - Intermediate-Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and intermediate-risk Intensification I, II, and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: Asparaginase Erwinia Chrysanthemi, Recombinant-Rywn (Drug)
AZA | + ADE | +FLAG+Ida+Sor| +AE+Sor | +MA+Sor | +Asp+AraC+Sor
Part 2 Dose Expansion with AZA - High Risk (no donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and high-risk Intensifications I, II and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: Cytarabine (Drug)
DAC |+ADE |+FLAG+Ida+Sor |+AE+Sor|+MA+Sor|+Asp+AraC+Sor
Part 2 Dose Expansion with DAC - High Risk (no donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and high-risk Intensifications I, II and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: Dexrazoxane (Drug)
AZA+ADE | AZA+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with AZA- High Risk (with donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Induction I Induction II and high-risk Intensifications I or high risk intensification III without azacitidine. Patients will proceed to stem cell transplant. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: azacitidine cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant.
干预措施: Sorafenib (Drug)
AZA+ADE | AZA+FLAG+Ida+Sor | AZA+AE+Sor | AZA+MA+Sor
Part 2 Dose Expansion with AZA - Low Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and low- risk Intensifications I & II. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, ITMHA.
干预措施: G-CSF (Drug)
AZA | + ADE | +FLAG+Ida+Sor| +AE+Sor | +MA+Sor | +Asp+AraC+Sor
Part 2 Dose Expansion with AZA - High Risk (no donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and high-risk Intensifications I, II and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: Dexrazoxane (Drug)
AZA |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor
Part 2 Dose Expansion with AZA - High Risk (with donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and high-risk Intensification I or high risk intensification III. Patients will proceed to stem cell transplant. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G-CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant.
干预措施: Sorafenib (Drug)
AZA+ADE | AZA+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with AZA- High Risk (with donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Induction I Induction II and high-risk Intensifications I or high risk intensification III without azacitidine. Patients will proceed to stem cell transplant. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: azacitidine cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant.
干预措施: Cytarabine (Drug)
DAC+ADE | DAC+FLAG+Ida+Sor | AE | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with DAC - High Risk (no donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive high-risk Intensifications I, II & III without decitabine. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, ITMHA.
干预措施: Cytarabine (Drug)
AZA+ADE | AZA+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with AZA- High Risk (with donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Induction I Induction II and high-risk Intensifications I or high risk intensification III without azacitidine. Patients will proceed to stem cell transplant. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: azacitidine cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant.
干预措施: G-CSF (Drug)
AZA | + ADE | +FLAG+Ida+Sor| +AE+Sor | +MA+Sor | +Asp+AraC+Sor
Part 2 Dose Expansion with AZA - High Risk (no donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and high-risk Intensifications I, II and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: Azacitidine (Drug)
AZA | + ADE | +FLAG+Ida+Sor| +AE+Sor | +MA+Sor | +Asp+AraC+Sor
Part 2 Dose Expansion with AZA - High Risk (no donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and high-risk Intensifications I, II and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: Asparaginase Erwinia Chrysanthemi, Recombinant-Rywn (Drug)
DAC |+ADE |+FLAG+Ida+Sor |+AE+Sor|+MA+Sor|+Asp+AraC+Sor
Part 2 Dose Expansion with DAC - High Risk (no donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and high-risk Intensifications I, II and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: Etoposide (Drug)
DAC|+ADE | +FLAG+Ida+Sor | +AE+Sor | +MA+Sor | +Asp+AraC+Sor
Part 2 Dose Expansion with DAC - Intermediate-Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and intermediate-risk Intensifications I, II and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: Sorafenib (Drug)
DAC |+ADE |+FLAG+Ida+Sor |+AE+Sor|+MA+Sor|+Asp+AraC+Sor
Part 2 Dose Expansion with DAC - High Risk (no donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and high-risk Intensifications I, II and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: Asparaginase Erwinia Chrysanthemi, Recombinant-Rywn (Drug)
DAC |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor
Part 2 Dose Expansion with DAC - High Risk (with donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and high-risk Intensifications I or high risk intensification III. Patients will proceed to stem cell transplant. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant
干预措施: Dexrazoxane (Drug)
AZA+ADE | AZA+FLAG+Ida | AE | MA
Part 1 Tolerability with AZA - Low Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and then receive low-risk intensifications I & II without azacitidine.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide,dexrazoxane, fludarabine, idarubicin, G-CSF, mitoxantrone., ITMHA.
干预措施: Azacitidine (Drug)
AZA+ADE | AZA+FLAG+Ida | AE | MA
Part 1 Tolerability with AZA - Low Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and then receive low-risk intensifications I & II without azacitidine.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide,dexrazoxane, fludarabine, idarubicin, G-CSF, mitoxantrone., ITMHA.
干预措施: Daunorubicin (Drug)
AZA+ADE | AZA+FLAG+Ida | AE | MA
Part 1 Tolerability with AZA - Low Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and then receive low-risk intensifications I & II without azacitidine.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide,dexrazoxane, fludarabine, idarubicin, G-CSF, mitoxantrone., ITMHA.
干预措施: Cytarabine (Drug)
AZA+ADE | AZA+FLAG+Ida | AE | MA
Part 1 Tolerability with AZA - Low Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and then receive low-risk intensifications I & II without azacitidine.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide,dexrazoxane, fludarabine, idarubicin, G-CSF, mitoxantrone., ITMHA.
干预措施: Etoposide (Drug)
AZA+ADE | AZA+FLAG+Ida | AE | MA
Part 1 Tolerability with AZA - Low Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and then receive low-risk intensifications I & II without azacitidine.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide,dexrazoxane, fludarabine, idarubicin, G-CSF, mitoxantrone., ITMHA.
干预措施: Idarubicin (Drug)
AZA+ADE | AZA+FLAG+Ida | AE | MA
Part 1 Tolerability with AZA - Low Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and then receive low-risk intensifications I & II without azacitidine.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide,dexrazoxane, fludarabine, idarubicin, G-CSF, mitoxantrone., ITMHA.
干预措施: Fludarabine (Drug)
AZA+ADE | AZA+FLAG+Ida | AE | MA
Part 1 Tolerability with AZA - Low Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and then receive low-risk intensifications I & II without azacitidine.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide,dexrazoxane, fludarabine, idarubicin, G-CSF, mitoxantrone., ITMHA.
干预措施: Mitoxantrone (Drug)
AZA+ADE | AZA+FLAG+Ida | AE | MA
Part 1 Tolerability with AZA - Low Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and then receive low-risk intensifications I & II without azacitidine.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide,dexrazoxane, fludarabine, idarubicin, G-CSF, mitoxantrone., ITMHA.
干预措施: G-CSF (Drug)
AZA+ADE | AZA+FLAG+Ida | AE | MA
Part 1 Tolerability with AZA - Low Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and then receive low-risk intensifications I & II without azacitidine.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide,dexrazoxane, fludarabine, idarubicin, G-CSF, mitoxantrone., ITMHA.
干预措施: Dexrazoxane (Drug)
DAC+ADE | DAC+FLAG+Ida | AE | MA
Part 1 Tolerability with DAC - Low Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive low-risk Intensifications I & II without decitabine.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, ITMHA.
干预措施: Decitabine (Drug)
DAC+ADE | DAC+FLAG+Ida | AE | MA
Part 1 Tolerability with DAC - Low Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive low-risk Intensifications I & II without decitabine.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, ITMHA.
干预措施: Cytarabine (Drug)
DAC+ADE | DAC+FLAG+Ida | AE | MA
Part 1 Tolerability with DAC - Low Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive low-risk Intensifications I & II without decitabine.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, ITMHA.
干预措施: Daunorubicin (Drug)
DAC+ADE | DAC+FLAG+Ida | AE | MA
Part 1 Tolerability with DAC - Low Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive low-risk Intensifications I & II without decitabine.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, ITMHA.
干预措施: Etoposide (Drug)
DAC+ADE | DAC+FLAG+Ida | AE | MA
Part 1 Tolerability with DAC - Low Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive low-risk Intensifications I & II without decitabine.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, ITMHA.
干预措施: Idarubicin (Drug)
DAC+ADE | DAC+FLAG+Ida | AE | MA
Part 1 Tolerability with DAC - Low Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive low-risk Intensifications I & II without decitabine.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, ITMHA.
干预措施: Mitoxantrone (Drug)
DAC+ADE | DAC+FLAG+Ida | AE | MA
Part 1 Tolerability with DAC - Low Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive low-risk Intensifications I & II without decitabine.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, ITMHA.
干预措施: Fludarabine (Drug)
DAC+ADE | DAC+FLAG+Ida | AE | MA
Part 1 Tolerability with DAC - Low Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive low-risk Intensifications I & II without decitabine.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, ITMHA.
干预措施: Dexrazoxane (Drug)
DAC+ADE | DAC+FLAG+Ida | AE | MA
Part 1 Tolerability with DAC - Low Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive low-risk Intensifications I & II without decitabine.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, ITMHA.
干预措施: G-CSF (Drug)
AZA+ADE | AZA+FLAG+Ida+Sor | AZA+AE+Sor | AZA+MA+Sor
Part 2 Dose Expansion with AZA - Low Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and low- risk Intensifications I & II. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, ITMHA.
干预措施: Azacitidine (Drug)
AZA+ADE | AZA+FLAG+Ida+Sor | AZA+AE+Sor | AZA+MA+Sor
Part 2 Dose Expansion with AZA - Low Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and low- risk Intensifications I & II. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, ITMHA.
干预措施: Cytarabine (Drug)
AZA+ADE | AZA+FLAG+Ida+Sor | AZA+AE+Sor | AZA+MA+Sor
Part 2 Dose Expansion with AZA - Low Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and low- risk Intensifications I & II. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, ITMHA.
干预措施: Daunorubicin (Drug)
AZA+ADE | AZA+FLAG+Ida+Sor | AZA+AE+Sor | AZA+MA+Sor
Part 2 Dose Expansion with AZA - Low Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and low- risk Intensifications I & II. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, ITMHA.
干预措施: Idarubicin (Drug)
AZA+ADE | AZA+FLAG+Ida+Sor | AZA+AE+Sor | AZA+MA+Sor
Part 2 Dose Expansion with AZA - Low Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and low- risk Intensifications I & II. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, ITMHA.
干预措施: Etoposide (Drug)
AZA+ADE | AZA+FLAG+Ida+Sor | AZA+AE+Sor | AZA+MA+Sor
Part 2 Dose Expansion with AZA - Low Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and low- risk Intensifications I & II. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, ITMHA.
干预措施: Fludarabine (Drug)
AZA+ADE | AZA+FLAG+Ida+Sor | AZA+AE+Sor | AZA+MA+Sor
Part 2 Dose Expansion with AZA - Low Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and low- risk Intensifications I & II. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, ITMHA.
干预措施: Mitoxantrone (Drug)
AZA+ADE | AZA+FLAG+Ida+Sor | AZA+AE+Sor | AZA+MA+Sor
Part 2 Dose Expansion with AZA - Low Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and low- risk Intensifications I & II. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, ITMHA.
干预措施: Sorafenib (Drug)
DAC+ADE | DAC+FLAG+Ida+Sor | DAC+AE+Sor|DAC+MA+Sor
Part 2 Dose Expansion with DAC - Low Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and low-risk Intensifications I & II. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, ITMHA.
干预措施: Daunorubicin (Drug)
DAC+ADE | DAC+FLAG+Ida+Sor | DAC+AE+Sor|DAC+MA+Sor
Part 2 Dose Expansion with DAC - Low Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and low-risk Intensifications I & II. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, ITMHA.
干预措施: Etoposide (Drug)
DAC+ADE | DAC+FLAG+Ida+Sor | DAC+AE+Sor|DAC+MA+Sor
Part 2 Dose Expansion with DAC - Low Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and low-risk Intensifications I & II. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, ITMHA.
干预措施: Fludarabine (Drug)
DAC+ADE | DAC+FLAG+Ida+Sor | DAC+AE+Sor|DAC+MA+Sor
Part 2 Dose Expansion with DAC - Low Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and low-risk Intensifications I & II. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, ITMHA.
干预措施: Sorafenib (Drug)
DAC+ADE | DAC+FLAG+Ida+Sor | DAC+AE+Sor|DAC+MA+Sor
Part 2 Dose Expansion with DAC - Low Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and low-risk Intensifications I & II. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, ITMHA.
干预措施: G-CSF (Drug)
DAC+ADE | DAC+FLAG+Ida+Sor | DAC+AE+Sor|DAC+MA+Sor
Part 2 Dose Expansion with DAC - Low Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and low-risk Intensifications I & II. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, ITMHA.
干预措施: Dexrazoxane (Drug)
AZA+ADE | AZA+FLAG+Ida | AE | MA | Asp+AraC
Part 1 Tolerability with AZA - Intermediate Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and then receive intermediate risk Intensifications I, II & III without azacitidine.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, erwinia asparaginase, ITMHA,
干预措施: Azacitidine (Drug)
AZA+ADE | AZA+FLAG+Ida | AE | MA | Asp+AraC
Part 1 Tolerability with AZA - Intermediate Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and then receive intermediate risk Intensifications I, II & III without azacitidine.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, erwinia asparaginase, ITMHA,
干预措施: Cytarabine (Drug)
AZA+ADE | AZA+FLAG+Ida | AE | MA | Asp+AraC
Part 1 Tolerability with AZA - Intermediate Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and then receive intermediate risk Intensifications I, II & III without azacitidine.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, erwinia asparaginase, ITMHA,
干预措施: Daunorubicin (Drug)
AZA+ADE | AZA+FLAG+Ida | AE | MA | Asp+AraC
Part 1 Tolerability with AZA - Intermediate Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and then receive intermediate risk Intensifications I, II & III without azacitidine.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, erwinia asparaginase, ITMHA,
干预措施: Etoposide (Drug)
AZA+ADE | AZA+FLAG+Ida | AE | MA | Asp+AraC
Part 1 Tolerability with AZA - Intermediate Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and then receive intermediate risk Intensifications I, II & III without azacitidine.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, erwinia asparaginase, ITMHA,
干预措施: Idarubicin (Drug)
AZA+ADE | AZA+FLAG+Ida | AE | MA | Asp+AraC
Part 1 Tolerability with AZA - Intermediate Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and then receive intermediate risk Intensifications I, II & III without azacitidine.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, erwinia asparaginase, ITMHA,
干预措施: Fludarabine (Drug)
AZA+ADE | AZA+FLAG+Ida | AE | MA | Asp+AraC
Part 1 Tolerability with AZA - Intermediate Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and then receive intermediate risk Intensifications I, II & III without azacitidine.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, erwinia asparaginase, ITMHA,
干预措施: Mitoxantrone (Drug)
AZA+ADE | AZA+FLAG+Ida | AE | MA | Asp+AraC
Part 1 Tolerability with AZA - Intermediate Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and then receive intermediate risk Intensifications I, II & III without azacitidine.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, erwinia asparaginase, ITMHA,
干预措施: Erwinia asparaginase (Drug)
AZA+ADE | AZA+FLAG+Ida | AE | MA | Asp+AraC
Part 1 Tolerability with AZA - Intermediate Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and then receive intermediate risk Intensifications I, II & III without azacitidine.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, erwinia asparaginase, ITMHA,
干预措施: G-CSF (Drug)
DAC+ADE | DAC+FLAG+Ida | AE | MA | Asp+AraC
Part 1 Tolerability with DAC - Intermediate Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive intermediate-risk Intensifications I, II & III without decitabine.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, erwinia asparaginase, ITMHA.
干预措施: Cytarabine (Drug)
AZA+ADE | AZA+FLAG+Ida | AE | MA | Asp+AraC
Part 1 Tolerability with AZA - Intermediate Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and then receive intermediate risk Intensifications I, II & III without azacitidine.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, erwinia asparaginase, ITMHA,
干预措施: Dexrazoxane (Drug)
DAC+ADE | DAC+FLAG+Ida | AE | MA | Asp+AraC
Part 1 Tolerability with DAC - Intermediate Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive intermediate-risk Intensifications I, II & III without decitabine.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, erwinia asparaginase, ITMHA.
干预措施: Decitabine (Drug)
DAC+ADE | DAC+FLAG+Ida | AE | MA | Asp+AraC
Part 1 Tolerability with DAC - Intermediate Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive intermediate-risk Intensifications I, II & III without decitabine.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, erwinia asparaginase, ITMHA.
干预措施: Daunorubicin (Drug)
DAC+ADE | DAC+FLAG+Ida | AE | MA | Asp+AraC
Part 1 Tolerability with DAC - Intermediate Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive intermediate-risk Intensifications I, II & III without decitabine.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, erwinia asparaginase, ITMHA.
干预措施: Fludarabine (Drug)
DAC+ADE | DAC+FLAG+Ida | AE | MA | Asp+AraC
Part 1 Tolerability with DAC - Intermediate Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive intermediate-risk Intensifications I, II & III without decitabine.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, erwinia asparaginase, ITMHA.
干预措施: Etoposide (Drug)
DAC+ADE | DAC+FLAG+Ida | AE | MA | Asp+AraC
Part 1 Tolerability with DAC - Intermediate Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive intermediate-risk Intensifications I, II & III without decitabine.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, erwinia asparaginase, ITMHA.
干预措施: Idarubicin (Drug)
DAC+ADE | DAC+FLAG+Ida | AE | MA | Asp+AraC
Part 1 Tolerability with DAC - Intermediate Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive intermediate-risk Intensifications I, II & III without decitabine.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, erwinia asparaginase, ITMHA.
干预措施: Mitoxantrone (Drug)
DAC+ADE | DAC+FLAG+Ida | AE | MA | Asp+AraC
Part 1 Tolerability with DAC - Intermediate Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive intermediate-risk Intensifications I, II & III without decitabine.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, erwinia asparaginase, ITMHA.
干预措施: Erwinia asparaginase (Drug)
DAC+ADE | DAC+FLAG+Ida | AE | MA | Asp+AraC
Part 1 Tolerability with DAC - Intermediate Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive intermediate-risk Intensifications I, II & III without decitabine.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, erwinia asparaginase, ITMHA.
干预措施: G-CSF (Drug)
DAC+ADE | DAC+FLAG+Ida | AE | MA | Asp+AraC
Part 1 Tolerability with DAC - Intermediate Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive intermediate-risk Intensifications I, II & III without decitabine.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, erwinia asparaginase, ITMHA.
干预措施: Dexrazoxane (Drug)
AZA| +ADE | +FLAG+Ida+Sor| +AE+Sor| +MA+Sor| +Asp+AraC+Sor
Part 2 Dose Expansion with AZA - Intermediate-Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and intermediate-risk Intensification I, II, and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: Daunorubicin (Drug)
AZA| +ADE | +FLAG+Ida+Sor| +AE+Sor| +MA+Sor| +Asp+AraC+Sor
Part 2 Dose Expansion with AZA - Intermediate-Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and intermediate-risk Intensification I, II, and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: Etoposide (Drug)
AZA| +ADE | +FLAG+Ida+Sor| +AE+Sor| +MA+Sor| +Asp+AraC+Sor
Part 2 Dose Expansion with AZA - Intermediate-Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and intermediate-risk Intensification I, II, and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: Idarubicin (Drug)
AZA| +ADE | +FLAG+Ida+Sor| +AE+Sor| +MA+Sor| +Asp+AraC+Sor
Part 2 Dose Expansion with AZA - Intermediate-Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and intermediate-risk Intensification I, II, and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: Fludarabine (Drug)
AZA| +ADE | +FLAG+Ida+Sor| +AE+Sor| +MA+Sor| +Asp+AraC+Sor
Part 2 Dose Expansion with AZA - Intermediate-Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and intermediate-risk Intensification I, II, and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: Mitoxantrone (Drug)
AZA| +ADE | +FLAG+Ida+Sor| +AE+Sor| +MA+Sor| +Asp+AraC+Sor
Part 2 Dose Expansion with AZA - Intermediate-Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and intermediate-risk Intensification I, II, and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: Erwinia asparaginase (Drug)
AZA| +ADE | +FLAG+Ida+Sor| +AE+Sor| +MA+Sor| +Asp+AraC+Sor
Part 2 Dose Expansion with AZA - Intermediate-Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and intermediate-risk Intensification I, II, and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: Sorafenib (Drug)
AZA| +ADE | +FLAG+Ida+Sor| +AE+Sor| +MA+Sor| +Asp+AraC+Sor
Part 2 Dose Expansion with AZA - Intermediate-Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and intermediate-risk Intensification I, II, and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: G-CSF (Drug)
AZA| +ADE | +FLAG+Ida+Sor| +AE+Sor| +MA+Sor| +Asp+AraC+Sor
Part 2 Dose Expansion with AZA - Intermediate-Risk
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and intermediate-risk Intensification I, II, and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: Dexrazoxane (Drug)
DAC|+ADE | +FLAG+Ida+Sor | +AE+Sor | +MA+Sor | +Asp+AraC+Sor
Part 2 Dose Expansion with DAC - Intermediate-Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and intermediate-risk Intensifications I, II and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: Decitabine (Drug)
DAC|+ADE | +FLAG+Ida+Sor | +AE+Sor | +MA+Sor | +Asp+AraC+Sor
Part 2 Dose Expansion with DAC - Intermediate-Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and intermediate-risk Intensifications I, II and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: Cytarabine (Drug)
DAC|+ADE | +FLAG+Ida+Sor | +AE+Sor | +MA+Sor | +Asp+AraC+Sor
Part 2 Dose Expansion with DAC - Intermediate-Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and intermediate-risk Intensifications I, II and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: Idarubicin (Drug)
DAC|+ADE | +FLAG+Ida+Sor | +AE+Sor | +MA+Sor | +Asp+AraC+Sor
Part 2 Dose Expansion with DAC - Intermediate-Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and intermediate-risk Intensifications I, II and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: Etoposide (Drug)
DAC|+ADE | +FLAG+Ida+Sor | +AE+Sor | +MA+Sor | +Asp+AraC+Sor
Part 2 Dose Expansion with DAC - Intermediate-Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and intermediate-risk Intensifications I, II and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: Fludarabine (Drug)
DAC|+ADE | +FLAG+Ida+Sor | +AE+Sor | +MA+Sor | +Asp+AraC+Sor
Part 2 Dose Expansion with DAC - Intermediate-Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and intermediate-risk Intensifications I, II and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: Mitoxantrone (Drug)
DAC|+ADE | +FLAG+Ida+Sor | +AE+Sor | +MA+Sor | +Asp+AraC+Sor
Part 2 Dose Expansion with DAC - Intermediate-Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and intermediate-risk Intensifications I, II and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: Erwinia asparaginase (Drug)
DAC|+ADE | +FLAG+Ida+Sor | +AE+Sor | +MA+Sor | +Asp+AraC+Sor
Part 2 Dose Expansion with DAC - Intermediate-Risk
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and intermediate-risk Intensifications I, II and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: G-CSF (Drug)
AZA+ADE | AZA+FLAG-Ida+Sor | AE | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with AZA - High Risk (no donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Induction I & II and high-risk intensifications I, II & III without azacitidine. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, ITMHA.
干预措施: Idarubicin (Drug)
AZA+ADE | AZA+FLAG-Ida+Sor | AE | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with AZA - High Risk (no donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Induction I & II and high-risk intensifications I, II & III without azacitidine. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, ITMHA.
干预措施: Mitoxantrone (Drug)
AZA+ADE | AZA+FLAG-Ida+Sor | AE | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with AZA - High Risk (no donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Induction I & II and high-risk intensifications I, II & III without azacitidine. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, ITMHA.
干预措施: G-CSF (Drug)
AZA+ADE | AZA+FLAG-Ida+Sor | AE | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with AZA - High Risk (no donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Induction I & II and high-risk intensifications I, II & III without azacitidine. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, ITMHA.
干预措施: Dexrazoxane (Drug)
DAC+ADE | DAC+FLAG+Ida+Sor | AE | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with DAC - High Risk (no donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive high-risk Intensifications I, II & III without decitabine. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, ITMHA.
干预措施: Decitabine (Drug)
DAC+ADE | DAC+FLAG+Ida+Sor | AE | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with DAC - High Risk (no donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive high-risk Intensifications I, II & III without decitabine. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, ITMHA.
干预措施: Daunorubicin (Drug)
DAC+ADE | DAC+FLAG+Ida+Sor | AE | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with DAC - High Risk (no donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive high-risk Intensifications I, II & III without decitabine. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, ITMHA.
干预措施: Etoposide (Drug)
DAC+ADE | DAC+FLAG+Ida+Sor | AE | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with DAC - High Risk (no donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive high-risk Intensifications I, II & III without decitabine. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, ITMHA.
干预措施: Idarubicin (Drug)
DAC+ADE | DAC+FLAG+Ida+Sor | AE | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with DAC - High Risk (no donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive high-risk Intensifications I, II & III without decitabine. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, ITMHA.
干预措施: Fludarabine (Drug)
DAC+ADE | DAC+FLAG+Ida+Sor | AE | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with DAC - High Risk (no donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive high-risk Intensifications I, II & III without decitabine. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, ITMHA.
干预措施: G-CSF (Drug)
DAC+ADE | DAC+FLAG+Ida+Sor | AE | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with DAC - High Risk (no donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive high-risk Intensifications I, II & III without decitabine. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, ITMHA.
干预措施: Erwinia asparaginase (Drug)
DAC+ADE | DAC+FLAG+Ida+Sor | AE | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with DAC - High Risk (no donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive high-risk Intensifications I, II & III without decitabine. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, ITMHA.
干预措施: Mitoxantrone (Drug)
DAC+ADE | DAC+FLAG+Ida+Sor | AE | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with DAC - High Risk (no donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive high-risk Intensifications I, II & III without decitabine. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, ITMHA.
干预措施: Sorafenib (Drug)
AZA | + ADE | +FLAG+Ida+Sor| +AE+Sor | +MA+Sor | +Asp+AraC+Sor
Part 2 Dose Expansion with AZA - High Risk (no donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and high-risk Intensifications I, II and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: Daunorubicin (Drug)
DAC+ADE | DAC+FLAG+Ida+Sor | AE | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with DAC - High Risk (no donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive high-risk Intensifications I, II & III without decitabine. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, ITMHA.
干预措施: Dexrazoxane (Drug)
AZA | + ADE | +FLAG+Ida+Sor| +AE+Sor | +MA+Sor | +Asp+AraC+Sor
Part 2 Dose Expansion with AZA - High Risk (no donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and high-risk Intensifications I, II and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: Etoposide (Drug)
AZA | + ADE | +FLAG+Ida+Sor| +AE+Sor | +MA+Sor | +Asp+AraC+Sor
Part 2 Dose Expansion with AZA - High Risk (no donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and high-risk Intensifications I, II and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: Idarubicin (Drug)
AZA | + ADE | +FLAG+Ida+Sor| +AE+Sor | +MA+Sor | +Asp+AraC+Sor
Part 2 Dose Expansion with AZA - High Risk (no donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and high-risk Intensifications I, II and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: Mitoxantrone (Drug)
AZA | + ADE | +FLAG+Ida+Sor| +AE+Sor | +MA+Sor | +Asp+AraC+Sor
Part 2 Dose Expansion with AZA - High Risk (no donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and high-risk Intensifications I, II and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: Fludarabine (Drug)
AZA | + ADE | +FLAG+Ida+Sor| +AE+Sor | +MA+Sor | +Asp+AraC+Sor
Part 2 Dose Expansion with AZA - High Risk (no donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and high-risk Intensifications I, II and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: Sorafenib (Drug)
AZA | + ADE | +FLAG+Ida+Sor| +AE+Sor | +MA+Sor | +Asp+AraC+Sor
Part 2 Dose Expansion with AZA - High Risk (no donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and high-risk Intensifications I, II and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: G-CSF (Drug)
DAC |+ADE |+FLAG+Ida+Sor |+AE+Sor|+MA+Sor|+Asp+AraC+Sor
Part 2 Dose Expansion with DAC - High Risk (no donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and high-risk Intensifications I, II and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: Idarubicin (Drug)
DAC |+ADE |+FLAG+Ida+Sor |+AE+Sor|+MA+Sor|+Asp+AraC+Sor
Part 2 Dose Expansion with DAC - High Risk (no donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and high-risk Intensifications I, II and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: Cytarabine (Drug)
DAC |+ADE |+FLAG+Ida+Sor |+AE+Sor|+MA+Sor|+Asp+AraC+Sor
Part 2 Dose Expansion with DAC - High Risk (no donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and high-risk Intensifications I, II and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: Daunorubicin (Drug)
DAC |+ADE |+FLAG+Ida+Sor |+AE+Sor|+MA+Sor|+Asp+AraC+Sor
Part 2 Dose Expansion with DAC - High Risk (no donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and high-risk Intensifications I, II and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: Mitoxantrone (Drug)
DAC |+ADE |+FLAG+Ida+Sor |+AE+Sor|+MA+Sor|+Asp+AraC+Sor
Part 2 Dose Expansion with DAC - High Risk (no donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and high-risk Intensifications I, II and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: Sorafenib (Drug)
DAC |+ADE |+FLAG+Ida+Sor |+AE+Sor|+MA+Sor|+Asp+AraC+Sor
Part 2 Dose Expansion with DAC - High Risk (no donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and high-risk Intensifications I, II and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: Erwinia asparaginase (Drug)
DAC |+ADE |+FLAG+Ida+Sor |+AE+Sor|+MA+Sor|+Asp+AraC+Sor
Part 2 Dose Expansion with DAC - High Risk (no donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and high-risk Intensifications I, II and III. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, sorafenib, mitoxantrone, erwinia asparaginase, asparaginase erwinia chrysanthemi (recombinant)-rywn, ITMHA.
干预措施: G-CSF (Drug)
AZA+ADE | AZA+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with AZA- High Risk (with donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Induction I Induction II and high-risk Intensifications I or high risk intensification III without azacitidine. Patients will proceed to stem cell transplant. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: azacitidine cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant.
干预措施: Etoposide (Drug)
AZA+ADE | AZA+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with AZA- High Risk (with donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Induction I Induction II and high-risk Intensifications I or high risk intensification III without azacitidine. Patients will proceed to stem cell transplant. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: azacitidine cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant.
干预措施: Mitoxantrone (Drug)
AZA+ADE | AZA+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with AZA- High Risk (with donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Induction I Induction II and high-risk Intensifications I or high risk intensification III without azacitidine. Patients will proceed to stem cell transplant. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: azacitidine cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant.
干预措施: Idarubicin (Drug)
AZA+ADE | AZA+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with AZA- High Risk (with donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Induction I Induction II and high-risk Intensifications I or high risk intensification III without azacitidine. Patients will proceed to stem cell transplant. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: azacitidine cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant.
干预措施: Erwinia asparaginase (Drug)
AZA+ADE | AZA+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with AZA- High Risk (with donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Induction I Induction II and high-risk Intensifications I or high risk intensification III without azacitidine. Patients will proceed to stem cell transplant. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: azacitidine cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant.
干预措施: Fludarabine (Drug)
AZA+ADE | AZA+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with AZA- High Risk (with donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Induction I Induction II and high-risk Intensifications I or high risk intensification III without azacitidine. Patients will proceed to stem cell transplant. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: azacitidine cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant.
干预措施: Dexrazoxane (Drug)
DAC+ADE | DAC+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with DAC - High Risk (with donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive high-risk Intensifications I or high risk intensification III without decitabine. Patients will proceed to stem cell transplant. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant
干预措施: Decitabine (Drug)
DAC+ADE | DAC+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with DAC - High Risk (with donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive high-risk Intensifications I or high risk intensification III without decitabine. Patients will proceed to stem cell transplant. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant
干预措施: Daunorubicin (Drug)
DAC+ADE | DAC+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with DAC - High Risk (with donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive high-risk Intensifications I or high risk intensification III without decitabine. Patients will proceed to stem cell transplant. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant
干预措施: Cytarabine (Drug)
DAC+ADE | DAC+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with DAC - High Risk (with donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive high-risk Intensifications I or high risk intensification III without decitabine. Patients will proceed to stem cell transplant. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant
干预措施: Etoposide (Drug)
DAC+ADE | DAC+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with DAC - High Risk (with donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive high-risk Intensifications I or high risk intensification III without decitabine. Patients will proceed to stem cell transplant. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant
干预措施: Idarubicin (Drug)
DAC+ADE | DAC+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with DAC - High Risk (with donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive high-risk Intensifications I or high risk intensification III without decitabine. Patients will proceed to stem cell transplant. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant
干预措施: Fludarabine (Drug)
DAC+ADE | DAC+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with DAC - High Risk (with donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive high-risk Intensifications I or high risk intensification III without decitabine. Patients will proceed to stem cell transplant. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant
干预措施: Mitoxantrone (Drug)
DAC+ADE | DAC+FLAG+Ida+Sor | MA+Sor | Asp+AraC+Sor
Part 1 Tolerability with DAC - High Risk (with donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and then receive high-risk Intensifications I or high risk intensification III without decitabine. Patients will proceed to stem cell transplant. Sorafenib is limited to patients with FLT3-ITD+/NUP98-NSD1+ or FLT3-ITD+/WT1mut somatic mutations.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant
干预措施: Erwinia asparaginase (Drug)
DAC |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor
Part 2 Dose Expansion with DAC - High Risk (with donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and high-risk Intensifications I or high risk intensification III. Patients will proceed to stem cell transplant. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant
干预措施: Daunorubicin (Drug)
DAC |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor
Part 2 Dose Expansion with DAC - High Risk (with donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and high-risk Intensifications I or high risk intensification III. Patients will proceed to stem cell transplant. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant
干预措施: Etoposide (Drug)
DAC |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor
Part 2 Dose Expansion with DAC - High Risk (with donor)
Patients are randomized to receive 5 days of single agent decitabine as part of Inductions I & II and high-risk Intensifications I or high risk intensification III. Patients will proceed to stem cell transplant. Sorafenib will be given to patients with FLT3-ITD. For these patients, DAC will be limited to the first two courses of Induction chemotherapy. They will not receive DAC with Intensification therapy.
Interventions: decitabine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G- CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant
干预措施: Mitoxantrone (Drug)
AZA |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor
Part 2 Dose Expansion with AZA - High Risk (with donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and high-risk Intensification I or high risk intensification III. Patients will proceed to stem cell transplant. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G-CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant.
干预措施: Etoposide (Drug)
AZA |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor
Part 2 Dose Expansion with AZA - High Risk (with donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and high-risk Intensification I or high risk intensification III. Patients will proceed to stem cell transplant. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G-CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant.
干预措施: Cytarabine (Drug)
AZA |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor
Part 2 Dose Expansion with AZA - High Risk (with donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and high-risk Intensification I or high risk intensification III. Patients will proceed to stem cell transplant. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G-CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant.
干预措施: Daunorubicin (Drug)
AZA |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor
Part 2 Dose Expansion with AZA - High Risk (with donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and high-risk Intensification I or high risk intensification III. Patients will proceed to stem cell transplant. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G-CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant.
干预措施: Idarubicin (Drug)
AZA |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor
Part 2 Dose Expansion with AZA - High Risk (with donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and high-risk Intensification I or high risk intensification III. Patients will proceed to stem cell transplant. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G-CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant.
干预措施: Fludarabine (Drug)
AZA |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor
Part 2 Dose Expansion with AZA - High Risk (with donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and high-risk Intensification I or high risk intensification III. Patients will proceed to stem cell transplant. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G-CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant.
干预措施: Mitoxantrone (Drug)
AZA |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor
Part 2 Dose Expansion with AZA - High Risk (with donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and high-risk Intensification I or high risk intensification III. Patients will proceed to stem cell transplant. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G-CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant.
干预措施: Erwinia asparaginase (Drug)
AZA |+ADE|+FLAG+Ida+Sor|+MA+Sor|+Asp+AraC+Sor
Part 2 Dose Expansion with AZA - High Risk (with donor)
Patients are randomized to receive 5 days of single agent azacitidine as part of Inductions I & II and high-risk Intensification I or high risk intensification III. Patients will proceed to stem cell transplant. Sorafenib will be given to patients with FLT3-ITD. For these patients, AZA will be limited to the first two courses of Induction chemotherapy. They will not receive AZA with Intensification therapy.
Interventions: azacitidine, cytarabine, daunorubicin, etoposide, dexrazoxane, fludarabine, idarubicin, G-CSF, mitoxantrone, sorafenib, ITMHA, erwinia asparaginase, stem cell transplant.
干预措施: Dexrazoxane (Drug)
结局指标
主要结局
Proportion of evaluable patients who tolerate five days of single agent DMTi before a standard chemotherapy combination
时间窗: From enrollment to completion of chemotherapy (up to 8 months after start of therapy)
Patients will be monitored for grade 4-5 non-hematologic toxic events during these two courses of chemotherapy. Tolerating a course is defined as completing the course without experiencing death or a grade 4 non-hematologic toxicity.
Change in genome-wide methylation burden of leukemia cells from diagnosis to after five days of single agent DMTi
时间窗: From diagnosis to completion of five days of single agent DMTi (up to 2 weeks after start of therapy)
Leukemic cells will be collected from patients at diagnosis and after five days of single agent DMTi. Each sample of leukemic cells will be profiled with a methylation microarray. For each leukemic sample, genome-wide methylation burden (GWMB) will be computed as the sum of methylation values across all markers. For each patient, the change in GWMB will be computed as the day 5 GWMB minus the diagnostic GWMB.
Cox model hazard ratio for association of event-free survival with genome-wide methylation burden
时间窗: From diagnosis to the first of the following events: death, relapse, resistant disease, second malignancy, or last follow-up (up to 3 years after completion of therapy)
Patients will be monitored for the events of interest from enrollment for at least three years. EFS will be defined as the time elapsed from enrollment to the first of the following events: death, relapse, resistant disease, or second malignancy. EFS times for subjects who have not experienced these events at the time of analysis will be censored at date of last follow-up. A Cox regression model will be used to evaluate the association of EFS with genome-wide methylation burden observed after completion of five days of single agent decitabine or azacitidine as randomly assigned.
次要结局
- Proportion of MRD-evaluable subjects with detectable minimal residual disease after receiving five days of a single agent DMTi followed by araC+daunorubicin+etoposide.(MRD will be measured after completion of DMTi+araC+daunorubicin+etoposide (up to 6 weeks after the start of therapy))
- Kaplan-Meier estimate of event-free survival(From diagnosis to the first of the following events: death, relapse, resistant disease, second malignancy, or last follow-up (up to 3 years after completion of therapy))
- Kaplan-Meier estimate of overall survival(From diagnosis to the first of the following events: death or last follow-up (up to 3 years after completion of therapy))