Clinical trial NCT01185886: Study of Blood and Tissue Samples in Children With Newly Diagnosed Acute Lymphoblastic Leukemia
Official title: Translational Research - Observational Study for Identification of New Possible Prognostic Factors and Future Therapeutic Targets in Children With Acute Lymphoblastic Leukemia (ALL)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Leukemia
Lymphoma
Keywords: untreated childhood acute lymphoblastic leukemia
L1 childhood acute lymphoblastic leukemia
L2 childhood acute lymphoblastic leukemia
B-cell childhood acute lymphoblastic leukemia
T-cell childhood acute lymphoblastic leukemia
stage I childhood lymphoblastic lymphoma
stage II childhood lymphoblastic lymphoma
stage III childhood lymphoblastic lymphoma
stage IV childhood lymphoblastic lymphoma
Philadelphia chromosome positive childhood precursor acute lymphoblastic leukemia
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2010-08-20
Enrollment: 1200
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER

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).

Eligibility criteria: 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

Primary outcomes:
measure: Event-free survival
measure: Disease-free interval from complete remission
measure: Response to pre-phase standard therapy
measure: Adverse events to induction standard therapy
measure: Overall survival
measure: Biomarker levels
Secondary outcomes:
Other outcomes:
Locations:
city: Antwerpen
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Brussels
country: Belgium
facility: Hopital Universitaire Des Enfants Reine Fabiola
city: Brussels
country: Belgium
facility: Universitair Ziekenhuis Brussel
city: Ghent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Leuven
country: Belgium
facility: U.Z. Leuven - Campus Gasthuisberg
city: Liege
country: Belgium
facility: Centre Hospitalier Regional De La Citadelle
city: Besancon
country: France
facility: CHRU de Besancon - Hopital Saint-Jacques
city: Caen
country: France
facility: CHU de Caen - Hopital Cote de Nacre
city: Grenoble
country: France
facility: CHU de Grenoble - La Tronche - Hôpital A. Michallon
city: Lille
country: France
facility: CHRU de Lille
city: Lyon
country: France
facility: Hospices Civils de Lyon
city: Montpellier
country: France
facility: Hopital Arnaud De Villeneuve
city: Nice
country: France
facility: CHU de Nice - Hopital De L'Archet
city: Paris
country: France
facility: CHU - Hopital Robert Debre
city: Poitiers
country: France
facility: Hopital Jean Bernard
city: Reims
country: France
facility: CHU de Reims - American Memorial Hospital
city: Saint-Denis
country: France
facility: Centre Hospitalier Félix Guyon
city: Strasbourg
country: France
facility: Hopitaux Universitaires de Strasbourg - Hautepierre
city: Toulouse
country: France
facility: CHU de Toulouse - C.H.U. De Toulouse - Hopital Des Enfants
city: Porto
country: Portugal
facility: Instituto Portugues De Oncologia - Centro Do Porto
Study officials:
affiliation: CHU - Hopital Robert Debre
name: Helene Cave
role: PRINCIPAL_INVESTIGATOR
affiliation: Universitair Ziekenhuis Gent
name: Yves Benoit, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospices Civils de Lyon
name: Yves Bertrand, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.