Clinical trial NCT04977895: Monitoring Minimal Residual Disease（MRD）in Pediatric B-acute Lymphoblastic Leukemia
Official title: A Study to Assess Minimal Residual Disease by Next-generation Sequencing of Immunoglobulin Gene Rearrangements in Pediatric B-acute Lymphoblastic Leukemia
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: B Acute Lymphoblastic Leukemia
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2021-07-27
Enrollment: 255
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients under age of 18 years with newly diagnosed B-ALL

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Age≤18 years.
2. Newly diagnosed B-ALL.
3. No previous treatment.
4. Signed informed consent in keeping with the policies of the hospital.

Exclusion Criteria:

1. History of other malignancies, except in situ carcinoma or malignancy treated with curative intent.
2. Patients with active or uncontrollable infections such as hepatitis B, hepatitis C or HIV infection.
3. Patients with uncontrolled autoimmune diseases or immune defects. Other protocol-defined Inclusion/Exclusion may apply.

Primary outcomes:
measure: The sensitivity of MRD detection by IgH V(D)J NGS and FCM
timeFrame: During Induction Phase: up to 3 months
measure: Relapse-free survival (RFS)
timeFrame: up to 5 years
Secondary outcomes:
measure: MRD dynamic
timeFrame: During Induction Phase: up to 3 months
measure: Overall survival (OS)
timeFrame: up to 5 years
measure: Event-free survival (EFS)
timeFrame: up to 5 years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Yi-Zhuo Zhang, MD
role: PRINCIPAL_INVESTIGATOR
References: