CHOA-AML: A Pilot Study for Newly Diagnosed Pediatric Patients With Acute Myeloid Leukemia (AML)

Emory University1 个研究点分布在 1 个国家目标入组 8 人开始时间: 2020年1月24日最近更新: 2022年6月15日

适应症

干预措施

试验速览

阶段: 2 期
状态: 终止
发起方: Emory University
入组人数: 8
试验地点: 1
主要终点: Event-free Survival (EFS) in Low Risk Patients and High Risk Patients

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

The investigators propose to study an Aflac-AML chemotherapy backbone prospectively to validate its use in all pediatric AML and to further evaluate the cardiotoxicity with this approach for low risk AML.

详细描述

Advances in risk stratification and therapy, have improved the event-free survival (EFS) and overall survival (OS) for pediatric acute myeloid leukemia (AML) to approximately 50% and 65% respectively, with current treatment strategies. Patients with good response to induction and/or those who lack high-risk cytogenetic and molecular features [classified as low-risk AML (LR-AML)] have even better outcomes with EFS and OS approaching 70% and 85% respectively; however, treatment-related toxicities remain a major concern. Anthracycline-based therapeutic regimens expose patients to the risk of anthracycline-induced cardiotoxicity. Therefore, strategies that reduce cardiac toxicities using tailored approaches while maintaining and/or improving outcomes are needed for all patients with AML. The Children's Oncology Group (COG) regimens AAML1031 and AAML0531 utilized an anthracycline-intensive backbone for LR-AML with cumulative anthracycline doxorubicin-equivalent doses of up to 492mg/m2. However, high-risk patients treated with chemotherapy alone received an intensified induction chemotherapy (using mitoxantrone-cytarabine) but with overall reduced doses of anthracycline-equivalent (342mg/m2). The investigators piloted an institutional practice to treat all LR-AML patients with four cycle regimen (Aflac-AML) with the goal of reducing cumulative anthracycline exposure, thereby reducing the risk of cardiotoxicity, while providing three high-dose cytarabine courses. In this pilot institutional experience with this approach, they were able to maintain excellent outcomes for this low-risk group with 3-year event-free survival (EFS) and OS of 70.0% ± 0.1% and 85.5% ± 0.08% respectively, from end of course 1. Recent evolution in cytogenetic classification has further delineated risk groups in AML. Gemtuzumab ozogamicin (GO), an antibody-drug conjugate was shown to reduce relapse risk in patients with CC genotype with de-novo AML on COG study AAML0531. The investigators propose to study an Aflac-AML chemotherapy backbone prospectively to validate its use in all pediatric AML and to further evaluate the cardiotoxicity with this approach for low risk AML.

研究设计

研究类型: Interventional
分配方式: Non Randomized
干预模型: Parallel
主要目的: Treatment
盲法: None

入排标准

年龄范围: — 至 21 Years（Child, Adult）
性别: All
接受健康志愿者: 否

入选标准

•Age: Patients must be less than 21 years of age at the time of study enrollment
•Diagnosis: Patients must be newly diagnosed with AML
•Patients with previously untreated primary AML who meet the customary criteria for AML with ≥ 20% bone marrow blasts as set out in the 2016 WHO Myeloid Neoplasm Classification are eligible.
•Attempts to obtain bone marrow either by aspirate or biopsy must be made unless clinically prohibitive. In cases where it is clinically prohibitive, peripheral blood with an excess of 20% blasts and in which adequate flow cytometric and cytogenetics/FISH testing is feasible can be substituted for the marrow exam at diagnosis.
•Patients with <20% bone marrow blasts are eligible if they have:
•A karyotypic abnormality characteristic of de novo AML (t(8;21)(q22;q22), inv(16)(p13q22) or t(16;16)(p13;q22) or 11q23 abnormalities,
•the unequivocal presence of megakaryoblasts, or
•Biopsy proven isolated myeloid sarcoma (myeloblastoma; chloroma, including leukemia cutis)
•Performance Level: Patients with acceptable organ function and any performance status are eligible for enrollment

排除标准

•Patients with any of the following constitutional conditions are not eligible:
•Fanconi anemia
•Shwachman syndrome
•Any other known bone marrow failure syndrome
•Patients with constitutional trisomy 21 or with constitutional mosaicism of trisomy 21 Note: Enrollment may occur, pending results of clinically indicated studies to exclude these conditions.
•Other Excluded Conditions:
•Any concurrent malignancy
•Juvenile myelomonocytic leukemia (JMML)
•Philadelphia chromosome positive AML
•Biphenotypic or bilineal acute leukemia
•Acute promyelocytic leukemia (APL)
•Acute myeloid leukemia arising from myelodysplasia
•Therapy-related myeloid neoplasms

研究组 & 干预措施

Aflac-AML Regimen for Low Risk AML Patients

Experimental

Participants in this arm will receive the standard Aflac-AML Regimen with the following chemotherapy:

Induction-1: patients on Induction-I will receive gemtuzumab + ADE therapy based on genotyping. Lasts a total of 28 days.
Induction II - MA
Intensification I - AE
Intensification II - HD ARAC/LASP

Patients with low risk status who had low risk markers and were MRD positive at the end of Induction I and continue to be MRD positive after Induction II will come off protocol.

干预措施: Cytarabine (Drug)

Aflac-AML Regimen for Low Risk AML Patients

Experimental

Participants in this arm will receive the standard Aflac-AML Regimen with the following chemotherapy:

Induction-1: patients on Induction-I will receive gemtuzumab + ADE therapy based on genotyping. Lasts a total of 28 days.
Induction II - MA
Intensification I - AE
Intensification II - HD ARAC/LASP

Patients with low risk status who had low risk markers and were MRD positive at the end of Induction I and continue to be MRD positive after Induction II will come off protocol.

干预措施: Daunorubicin (Drug)

Aflac-AML Regimen for Low Risk AML Patients

Experimental

Participants in this arm will receive the standard Aflac-AML Regimen with the following chemotherapy:

Induction-1: patients on Induction-I will receive gemtuzumab + ADE therapy based on genotyping. Lasts a total of 28 days.
Induction II - MA
Intensification I - AE
Intensification II - HD ARAC/LASP

Patients with low risk status who had low risk markers and were MRD positive at the end of Induction I and continue to be MRD positive after Induction II will come off protocol.

干预措施: Erwinase (Drug)

Aflac-AML Regimen for Low Risk AML Patients

Experimental

Participants in this arm will receive the standard Aflac-AML Regimen with the following chemotherapy:

Induction-1: patients on Induction-I will receive gemtuzumab + ADE therapy based on genotyping. Lasts a total of 28 days.
Induction II - MA
Intensification I - AE
Intensification II - HD ARAC/LASP

Patients with low risk status who had low risk markers and were MRD positive at the end of Induction I and continue to be MRD positive after Induction II will come off protocol.

干预措施: Etoposide (Drug)

Aflac-AML Regimen for Low Risk AML Patients

Experimental

Participants in this arm will receive the standard Aflac-AML Regimen with the following chemotherapy:

Induction-1: patients on Induction-I will receive gemtuzumab + ADE therapy based on genotyping. Lasts a total of 28 days.
Induction II - MA
Intensification I - AE
Intensification II - HD ARAC/LASP

Patients with low risk status who had low risk markers and were MRD positive at the end of Induction I and continue to be MRD positive after Induction II will come off protocol.

干预措施: Gemtuzumab ozogamicin (Drug)