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

Lymphoma Clinical Trial

Official title:

Translational Research - Observational Study for Identification of New Possible Prognostic Factors and Future Therapeutic Targets in Children With Acute Lymphoblastic Leukemia (ALL)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01185886
• Other study ID #: EORTC-58081
• Secondary ID: EORTC-58081EU-21
• Status: Active, not recruiting
• Phase: N/A
• First received: August 19, 2010
• Last updated: July 26, 2017
• Start date: June 2011
• Est. completion date: June 2021

Study information

• Verified date: July 2017
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1200
• Est. completion date: June 2021
• Est. primary completion date: June 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 17 Years

Eligibility

DISEASE CHARACTERISTICS:

• Newly diagnosed acute lymphoblastic leukemia (ALL), meeting the following criteria:

• FAB L1 or L2 morphology (any immunophenotype) and acute leukemias of ambiguous lineage (including biphenotypic or bilineal acute lymphoblastic leukemia)

• Patients with mature B-cell acute lymphoblastic leukemia (B-ALL) (FAB L3 morphology and immunophenotypical mature B phenotype or B-ALL with documented presence of karyotype t(8;14), t(2;8) t(8;22) or breakpoints as in mature B-ALL) are excluded from this study

• 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

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphoid
• Lymphoma
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Genetic:
• gene expression analysis

• mutation analysis

• polymorphism analysis

Other:
• biologic sample preservation procedure

• laboratory biomarker analysis

• pharmacogenomic studies

Locations

Country	Name	City	State
Belgium	Universitair Ziekenhuis Antwerpen	Antwerpen
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	Liege
France	CHRU de Besancon - Hopital Saint-Jacques	Besancon
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
Portugal	Instituto Portugues De Oncologia - Centro Do Porto	Porto

Sponsors (1)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC

Countries where clinical trial is conducted

Belgium,  France,  Portugal, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-free survival
Primary	Disease-free interval from complete remission
Primary	Response to pre-phase standard therapy
Primary	Adverse events to induction standard therapy
Primary	Overall survival
Primary	Biomarker levels