Clinical trial NCT02618109: Identification of New Immune Factors Specific of Relapse in Childhood B Lineage Acute Lymphoblastic Leukemia
Official title: Identification of New Immune Factors Specific of Relapse in Childhood B Lineage Acute Lymphoblastic Leukemia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: B Acute Lymphoblastic Leukemia
Leukemia Relapse
Keywords: B acute lymphoblastic leukemia
leukemia relapse
pediatric onco-hematology
Lead sponsor: University Hospital, Angers
Sponsor class: OTHER_GOV
First posted: 2015-12-01
Enrollment: 119
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: B-acute lymphoblastic leukaemia (ALL) is the most common childhood malignancy. Despite enhancement of childhood B-ALL outcome, relapses remain difficult to treat. Several studies in adult acute myeloid leukaemia have shown that proliferation of immunosuppressive cells -particularly T regulatory (Treg) cells and deficient natural killer (NK) cells- was associated with poor response to chemotherapy. However, few studies have been done on childhood ALL and none on relapse of B-ALL. Moreover, a newly described immunosuppressive B cells subset (Breg cells) seems to have a role in oncogenesis in mice model, but its significance has never been evaluated in human cancers. The purpose of this study is to prospectively evaluate the immune status of children newly diagnosed with first relapse of B-cell ALL, and to compare results with those of children treated for B-ALL in complete remission. Classic lymphocytic phenotype, proportions of immunosuppressive cells (Treg cells, deficient NK cells, Cytotoxic T-lymphocyte-associated protein 4 and/or Programmed T cell death 1) and thymopoiesis will be evaluated. The investigators assume that increase of immunosuppressive cells proportions could be associated with B-ALL relapse.


Eligibility criteria: 1. Inclusion Criteria for relapse Group :

   * Children aged from 1 to 18 years at the time of first B-ALL relapse diagnosis
   * Obtention of oral and written consent of the parents
   * Parents affiliated with the social security system
2. Inclusion Criteria for control Group :

   * Children aged from 1 to 18 years enrolled into FRALLE or EORTC treatment protocols, treated for B-ALL and who are in complete molecular remission
   * Obtention of oral and written consent of the parents
   * Parents affiliated with the social security system
3. Exclusion criteria for control Group are the same as for relapsed Group :

   * Children with hematologic syndrome predisposing to hematologic neoplasia (such as Fanconi's anaemia, Diamond Blackfan anaemia ...) or acute leukemia secondary to previous treatment, or who have had allogenic hematopoietic stem cell transplantation before relapse

Primary outcomes:
measure: Measure of Treg (CD4+,CD25+, Foxp3+) and deficient natural killer (NK) cells (CD3-,CD56+,NKp30-) proportions by FACS in children newly diagnosed with their first relapse of B-ALL.
timeFrame: At the time of the inclusion.
Secondary outcomes:
measure: Measure of the number of T CD4+ lymphocytes (Cluster of Differentiation 4), T CD8+ lymphocytes (Cluster of Differentiation 8), NK cells and Natural killer T (NKT) cells by FACS.
timeFrame: At the time of the inclusion.
measure: Measure of percentage of TCD4+ naive and memory cells and TCD8+ naive and memory cells by FACS.
timeFrame: At the time of the inclusion.
measure: Measure of percentage of gamma delta and alpha-bêta TCR CD3+ T cells by FACS.
timeFrame: At the time of the inclusion.
measure: Measure of TRECs (T cell receptor excision circle) by QPCR and naïve CD4+CD45RA+CD31+ T cells by FACS.
timeFrame: At the time of the inclusion.
Other outcomes:
Locations:
city: Amiens
country: France
facility: University Hospital of Amiens
city: Angers
country: France
facility: University Hospital of Angers
city: Besançon
country: France
facility: University Hospital of Besancon
city: Bordeaux
country: France
facility: University Hospital of Bordeaux
city: Caen
country: France
facility: University Hospital of Caen
city: Lyon
country: France
facility: Civil Hospices of Lyon
city: Marseille
country: France
facility: University Hospital of Marseille
city: Nancy
country: France
facility: University Hospital of Nancy
city: Nantes
country: France
facility: University Hospital of Nantes
city: Nice
country: France
facility: University Hospital of Nice
city: Paris
country: France
facility: University Hospital of Trousseau (Paris)
city: Paris
country: France
facility: University Hospital of Robert Debre (Paris)
city: Reims
country: France
facility: University Hospital of Reims
city: Rennes
country: France
facility: University Hospital of Rennes
city: Saint-Étienne
country: France
facility: University Hospital of Saint Etienne
city: Strasbourg
country: France
facility: University Hospital of Strasbourg
city: Toulouse
country: France
facility: University Hospital of Toulouse
city: Tours
country: France
facility: University Hospital of Tours
Study officials:
affiliation: UNIVERSITY HOSPITAL OF ANGERS
name: Isabelle PELLIER, PU-PH
role: PRINCIPAL_INVESTIGATOR
References: