Study of Blood and Tissue Samples in Children With Newly Diagnosed Acute Lymphoblastic Leukemia

NCT ID: NCT01185886

Last Updated: 2017-07-28

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 1200 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2011-06-30
• Study Completion Date: 2021-06-30

Brief Summary

RATIONALE: Collecting and storing samples of tumor tissue, blood, bone marrow, and other body fluids from patients to test in the laboratory and collecting information about the patient's health and treatment may help doctors learn more about cancer and help the study of cancer in the future. Studying these samples in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer. It may also help doctors predict how patients will respond to treatment.

PURPOSE: This research study is collecting and looking at blood and tissue samples in children with newly diagnosed acute lymphoblastic leukemia.

Detailed Description

OBJECTIVES:

• Collect clinical data in parallel with biological data and samples from children with newly diagnosed acute lymphoblastic leukemia for biobanking, and use part of the biobanked material to perform specific translational projects to achieve objectives II-IV.
• To identify new prognostic factors (e.g., minimal-residual disease [MRD] significance in small subgroups, miRNAs expression profile, PAX5 mutation, genetic abnormalities in T-cell acute lymphoblastic leukemia [T-ALL], and RAS pathway activation) and future therapeutic targets in children with newly diagnosed acute lymphoblastic leukemia.
• To identify leukemia cell genetic alterations (e.g., mutations in T-ALL and miRNA expression in B-cell acute lymphoblastic leukemia [B-ALL]) and related molecular pathways (e.g., RAS pathway) underlying leukemogenesis.
• To identify patient pharmacogenetic polymorphisms impacting individual response to corticosteroids as part of standard therapy and investigate their prognostic significance.

OUTLINE: This is a prospective observational biobanking study.

Patients undergo clinical evaluation, laboratory tests, and imaging periodically. Data are collected before, during, and after first-line standard therapy. Clinical data are collected from all patients in parallel with the biological data and samples. Biological samples are partly used to perform specific translational research (TR) projects. Remaining biological materials are stored for future research.

The following TR projects are performed on the biological samples for this study. Biological samples are analyzed for allele-specific amplification of Ig/TCR clonal rearrangements to quantify minimal-residual disease (MRD) via real-time PCR (TR1 Project); miRNA expression via qPCR (TR 2 Project); the detection of main point mutations via high-resolution melting PCR (TR 3 Project); genetic polymorphisms via real-time TaqMan allelic-discrimination method (TR 4 Project); clinical significance of genetic abnormalities via quantitative real-time RT-PCR, direct sequencing, and fluorescence in situ hybridization (TR 5 Project); and RAS pathway activation via single-nucleotide polymorphism (SNP) analysis and gene-expression analysis (TR 6 Project).

Conditions

Leukemia; Lymphoma

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: OTHER

Interventions

gene expression analysis

Intervention Type: GENETIC

mutation analysis

Intervention Type: GENETIC

polymorphism analysis

Intervention Type: GENETIC

biologic sample preservation procedure

Intervention Type: OTHER

laboratory biomarker analysis

Intervention Type: OTHER

pharmacogenomic studies

Intervention Type: OTHER

Eligibility Criteria

Exclusion Criteria

• Patients must also meet the following criteria for participating in individual translational research (TR) project:

• TR 1 project (MRD prognostic significance in small ALL subgroups):

• All patients, categorized according to response to pre-phase (< or > 1,000 peripheral blasts/mm³ at day 8) and minimal-residual disease (MRD) level at end of the induction therapy
• iAmp(21q) detected at presentation
• Hypodiploidy detected at presentation by karyotype and/or fluorescence in situ hybridization (FISH) and/or DNA index
• TR 2 project (miRNAs expression in pediatric ALL):

• Initially, average-risk 1 (AR1) patients
• In a second stage, the analysis might be extended to low-risk patients that still show treatment failure and high-risk ALL patients
• TR 3 project (Prognostic value of newly described mutations in childhood B-ALL)

• Initially, only B-cell precursor ALL patients
• TR 4 project (Pharmacogenetics of the response to prephase and induction therapy):

• All ALL patients
• TR 5 project (Clinical significance of genetic abnormalities in childhood T-ALL) :

• All patients with T-cell ALL, as defined by expression of T-cell surface antigens
• TR 6 project (RAS pathway activation in childhood B-ALL):

• All patients with B-lineage ALL
• Patients with Philadelphia-chromosome positive ALL (documented presence of t(9;22)(q34;q11) and/or of the BCR/ABL fusion transcript) are eligible
• Scheduled to receive therapy as per institutional standard practice and have not started therapy (except for a maximum of 7 days of systemic corticosteroids prior to diagnosis)
• May only be registered to this study once

PATIENT CHARACTERISTICS:

• No psychological, familial, sociological, or geographical condition potentially hampering participation in the study protocol and follow-up schedule
• Patients with Down syndrome are eligible

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Helene Cave

Role: PRINCIPAL_INVESTIGATOR

CHU - Hopital Robert Debre

Yves Benoit, MD

Role: PRINCIPAL_INVESTIGATOR

University Ghent

Yves Bertrand, MD

Role: PRINCIPAL_INVESTIGATOR

Hospices Civils de Lyon

Locations

Universitair Ziekenhuis Antwerpen

Antwerp, , Belgium

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

Hopital Universitaire Des Enfants Reine Fabiola

Brussels, , Belgium

Universitair Ziekenhuis Brussel

Brussels, , Belgium

Universitair Ziekenhuis Gent

Ghent, , Belgium

U.Z. Leuven - Campus Gasthuisberg

Leuven, , Belgium

Centre Hospitalier Regional De La Citadelle

Liège, , Belgium

CHRU de Besancon - Hopital Saint-Jacques

Besançon, , France

CHU de Caen - Hopital Cote de Nacre

Caen, , France

CHU de Grenoble - La Tronche - Hôpital A. Michallon

Grenoble, , France

CHRU de Lille

Lille, , France

Hospices Civils de Lyon

Lyon, , France

Hopital Arnaud De Villeneuve

Montpellier, , France

CHU de Nice - Hopital De L'Archet

Nice, , France

CHU - Hopital Robert Debre

Paris, , France

Hopital Jean Bernard

Poitiers, , France

CHU de Reims - American Memorial Hospital

Reims, , France

Centre Hospitalier Félix Guyon

Saint-Denis, , France

Hopitaux Universitaires de Strasbourg - Hautepierre

Strasbourg, , France

CHU de Toulouse - C.H.U. De Toulouse - Hopital Des Enfants

Toulouse, , France

Instituto Portugues De Oncologia - Centro Do Porto

Porto, , Portugal

Countries

Belgium; France; Portugal

References

Matthijssens F, Sharma ND, Nysus M, Nickl CK, Kang H, Perez DR, Lintermans B, Van Loocke W, Roels J, Peirs S, Demoen L, Pieters T, Reunes L, Lammens T, De Moerloose B, Van Nieuwerburgh F, Deforce DL, Cheung LC, Kotecha RS, Risseeuw MD, Van Calenbergh S, Takarada T, Yoneda Y, van Delft FW, Lock RB, Merkley SD, Chigaev A, Sklar LA, Mullighan CG, Loh ML, Winter SS, Hunger SP, Goossens S, Castillo EF, Ornatowski W, Van Vlierberghe P, Matlawska-Wasowska K. RUNX2 regulates leukemic cell metabolism and chemotaxis in high-risk T cell acute lymphoblastic leukemia. J Clin Invest. 2021 Mar 15;131(6):e141566. doi: 10.1172/JCI141566.

Reference Type: DERIVED

PMID: 33555272 (View on PubMed)

Other Identifiers

EORTC-58081

Identifier Type: -

Identifier Source: secondary_id

EU-21057

Identifier Type: -

Identifier Source: secondary_id

EORTC-58081

Identifier Type: -

Identifier Source: org_study_id