A Study to Assess Minimal Residual Disease by Next-generation Sequencing of Immunoglobulin Gene Rearrangements in Pediatric B-acute Lymphoblastic Leukemia
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 255
- 试验地点
- 1
- 主要终点
- The sensitivity of MRD detection by IgH V(D)J NGS and FCM
研究概览
简要总结
This study aimed to investigate the performance of next-generation sequencing (NGS) techniques measuring immunoglobulin heavy chain (IgH)-variable, diversity, and joining (V[D]J) clonal rearrangements （IgH-V[D]J NGS） compared with flow cytometry (FCM) in detecting of minimal residual disease (MRD) for children with acute lymphoblastic leukemia treated with South Chinese Children Leukemia Group (SCCLG)-ALL 2016, and to predict the relapse of the disease in the early stage and to assess the prognosis, so as to provide the basis for early intervention treatment and reduce the hematological relapse and improve the survival rate.
详细描述
The measurement of residual leukemia levels, "minimal residual disease" (MRD), during therapy has now emerged as the most important predictor the outcome in acute lymphoblastic leukemia (ALL). As a result, risk-classifications based on MRD assessment has become an essential part of determining disease risk and directing therapeutic approach for children and adults with ALL.
Recently, next-generation sequencing (NGS) techniques measuring immunoglobulin (Ig) or T-cell receptor (TCR) clonal rearrangements as a method of detecting MRD have been introduced. These approaches expand the sensitivity of MRD detection to as high as 1 in 10,000,000 cells and have been shown to be predictive of relapse in children with ALL receiving standard chemotherapy.
In this study, the investigators will determine the sensitivity and specificity of IgH-V(D)J NGS and compared its capacity to measure MRD with that of flow cytometry using diagnostic and follow-up samples from more than 100 patients with ALL. Patients under age of 18 years with newly diagnosed ALL will be recruited and receive the treatment strategy of (SCCLG)-ALL 2016. After identifying a trackable clone in diagnostic samples (Baseline), MRD was measured using IgH-V(D)J NGS and FCM on bone marrow at 3 time-points: fifteen days after induction therapy (D15), thirty-three days after induction therapy (D33) and then at the end of induction therapy. Event-free survival (EFS), Relapse-free survival (RFS) and overall survival (OS) were assessed.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- — 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age≤18 years.
- •Newly diagnosed B-ALL.
- •No previous treatment.
- •Signed informed consent in keeping with the policies of the hospital.
排除标准
- •History of other malignancies, except in situ carcinoma or malignancy treated with curative intent.
- •Patients with active or uncontrollable infections such as hepatitis B, hepatitis C or HIV infection.
- •Patients with uncontrolled autoimmune diseases or immune defects. Other protocol-defined Inclusion/Exclusion may apply.
结局指标
主要结局
The sensitivity of MRD detection by IgH V(D)J NGS and FCM
时间窗: During Induction Phase: up to 3 months
The percentage of participants with MRD positive status from baseline to induction treatment completion determined by by IgH V(D)J NGS and FCM
Relapse-free survival (RFS)
时间窗: up to 5 years
RFS was estimated from the date of diagnosis until the date of relapse at any site. For other participants, last follow-up available was taken as last control. If participant did not complete study, date of last visit available was considered.
次要结局
- MRD dynamic(During Induction Phase: up to 3 months)
- Event-free survival (EFS)(up to 5 years)
- Overall survival (OS)(up to 5 years)
研究者
Yizhuo Zhang
Professor
Sun Yat-sen University