LABMI: Identification of New Immune Factors Specific of Relapse in Childhood B Lineage Acute Lymphoblastic Leukemia

Sponsor

University Hospital, Angers (Other)

Overall Status

Unknown status

CT.gov ID

NCT02618109

Collaborator

(none)

120

Enrollment

Locations

Arms

Anticipated Duration (Months)

6.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
B Acute Lymphoblastic Leukemia Leukemia Relapse	Biological: Collection of blood samples	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

Identification of New Immune Factors Specific of Relapse in Childhood B Lineage Acute Lymphoblastic Leukemia

Actual Study Start Date :

Jan 1, 2016

Anticipated Primary Completion Date :

Jul 1, 2021

Anticipated Study Completion Date :

Jul 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Other: Relapse Group Collection of blood samples will be done in newly diagnosed relapse of B-ALL children at the time of relapse diagnosis. Children aged from 1 to 18 years at the time of first B-ALL relapse diagnosis.	Biological: Collection of blood samples Collection of blood samples
Other: Control Group Collection of blood samples will be done at the same stage of treatment as the relapse group has been collected. Children aged from 1 to 18 years enrolled into FRALLE (protocol of treatment) or EORTC (European Organisation for Research and Treatment of Cancer) treatment protocols, treated for B-ALL and who are in complete molecular remission. These control patients will be recruited at the same time from the beginning of B-ALL treatment as paired-relapsed control patients.	Biological: Collection of blood samples Collection of blood samples

Arm

Intervention/Treatment

Other: Relapse Group

Collection of blood samples will be done in newly diagnosed relapse of B-ALL children at the time of relapse diagnosis. Children aged from 1 to 18 years at the time of first B-ALL relapse diagnosis.

Biological: Collection of blood samples

Collection of blood samples

Other: Control Group

Collection of blood samples will be done at the same stage of treatment as the relapse group has been collected. Children aged from 1 to 18 years enrolled into FRALLE (protocol of treatment) or EORTC (European Organisation for Research and Treatment of Cancer) treatment protocols, treated for B-ALL and who are in complete molecular remission. These control patients will be recruited at the same time from the beginning of B-ALL treatment as paired-relapsed control patients.

Biological: Collection of blood samples

Collection of blood samples

Outcome Measures

Primary Outcome Measures

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. [At the time of the inclusion.]
Comparison of the immune status of patients at the diagnosis of their first relapse diagnosis with those of children treated for B-ALL who are in complete remission and at the same stage of treatment.

Secondary Outcome Measures

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. [At the time of the inclusion.]
Measure of percentage of TCD4+ naive and memory cells and TCD8+ naive and memory cells by FACS. [At the time of the inclusion.]
Measure of percentage of gamma delta and alpha-bêta TCR CD3+ T cells by FACS. [At the time of the inclusion.]
Measure of TRECs (T cell receptor excision circle) by QPCR and naïve CD4+CD45RA+CD31+ T cells by FACS. [At the time of the inclusion.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

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

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	University Hospital of Amiens	Amiens	France	80054
2	University Hospital of Angers	Angers	France	49933
3	University Hospital of Besancon	Besançon	France	25030
4	University Hospital of Bordeaux	Bordeaux	France	33000
5	University Hospital of Caen	Caen	France	14033
6	Civil Hospices of Lyon	Lyon	France	69008
7	University Hospital of Marseille	Marseille	France	13385
8	University Hospital of Nancy	Nancy	France	54511
9	University Hospital of Nantes	Nantes	France	44000
10	University Hospital of Nice	Nice	France	06202
11	University Hospital of Trousseau (Paris)	Paris	France	75571
12	University Hospital of Robert Debre (Paris)	Paris	France	75935
13	University Hospital of Reims	Reims	France	51092
14	University Hospital of Rennes	Rennes	France	35203
15	University Hospital of Saint Etienne	Saint-Étienne	France	42055
16	University Hospital of Strasbourg	Strasbourg	France	67098
17	University Hospital of Toulouse	Toulouse	France	31059
18	University Hospital of Tours	Tours	France	37000