Immunomonitoring of Children With Neuroblastoma (Immuneuro)

This study is currently recruiting participants.
Verified January 2014 by Centre Leon Berard
Sponsor:
Information provided by (Responsible Party):
Centre Leon Berard
ClinicalTrials.gov Identifier:
NCT01295762
First received: February 11, 2011
Last updated: January 30, 2014
Last verified: January 2014
  Purpose

Apart from brain tumors, Neuroblastoma is the most common solid tumor during childhood. About 50% of the cases present at diagnosis with factors of bad prognosis. During the last two decades, despite increased therapeutic intensity during induction and consolidation of high-risk neuroblastomas, the 5 year overall survival of high risk neuroblastoma remains in between 30 to 40% depending on studies.

Besides strategies of high-dose chemotherapy followed by autologous transplantation of hematopoietic stem cells, and differentiating molecules (retinoids), immunotherapy will become one of the leading anti-neuroblastoma targeted therapy. No therapeutic strategies or molecules obtained such gains of survival ever before.

Studying the immune system of children with neuroblastoma at diagnosis and during their treatment will help us to determine when we should test active or passive immunotherapy strategies. Moreover, this study would allow us to specify the cause of tumor immune tolerance in neuroblastoma, on which we have few data in comparison to adult tumors.

This will be a multicentric, pilot, prospective, open, study that will not require unusual diagnostic interventions. This study will be transversal (all neuroblastoma stages included) in order to determine comparative criteria between low and high risk neuroblastoma. It will also be longitudinal (from diagnosis to post-treatment follow-up) in order to specify evolutionary aspects of immunity under radio-chemotherapy and retinoic acid therapy.

Immunological analyses will be done on blood, bone marrow and tumor samples, at diagnosis, and during the treatment of children diagnosed for neuroblastoma (up to 3 time points). These types of samples are routinely done during conventional neuroblastoma treatment.


Condition Intervention
Neuroblastoma
Other: Immunological analyses

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Screening
Official Title: Immunomonitoring of Children With Neuroblastoma for the Development of Antitumor Immunotherapy Strategies

Resource links provided by NLM:


Further study details as provided by Centre Leon Berard:

Primary Outcome Measures:
  • Description of immune effectors in the blood, marrow and tumor diagnosis. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Rate effectors immunitaires in blood, marrow and tumor present at diagnosis


Estimated Enrollment: 30
Study Start Date: May 2011
Estimated Study Completion Date: May 2019
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Type of neuroblastoma
Neonatal stages I Localized immediately resectable stages Localized immediately unresectable stages High-risk neuroblastoma Relapsed neuroblastoma
Other: Immunological analyses
Immunological analyses will be done on blood, bone marrow and tumor samples, at diagnosis, and during the treatment of children diagnosed for neuroblastoma (up to 3 time points). These types of samples are routinely done during conventional neuroblastoma treatment.
Other Name: No intervention other names

Detailed Description:

The main objective of the study is the description of immune effectors in the blood, marrow and tumor diagnosis.

During 3 years, this trial will include 30 children from pediatric oncology units of Lyon, Saint-Etienne, Grenoble and Clermont-Ferrand.

The study duration is 5 years. Children follow-up scheduled for at least 2 years in order to determine predictive factors of therapeutic efficiency and survival.

Multi-parametric marker sets (6-8 markers per sample) have already developed and validated for analyzing the absolute amount and proportion of immune subpopulations (B, TCD4+, TCD8+, Treg, NK, DC) and activation status (PD1, ICOS, CD39, CD73, CD62L, CCR7, CD45RO, CD45RA, CD86, Ox40, CD137, CTLA4) on a small volume. At least, these analyses will be performed on each blood and marrow sample. If the amount of blood and mononuclear cells harvested allows it, functional analyses will be undertaken (intracytoplasmic cytokines in response to activation for T, DC, NK; protocols been set up).

Immunostainings will be performed on tumor samples at diagnosis and after resection of the primary tumor, in order to determine the expression and evolution of several immunomodulatory molecules on neuroblastoma cells (HLA class I & II, HLA-G, IDO, IL10,…)., and also determine the immune infiltrate within the tumor microenvironment (lymphocytes Treg, cellules dendritiques, MDSC,…). The techniques used will mostly be those of classical immunology (IHC, IF, FACS), and have already been set-up in our INSERM team for adult tumors.

Children's plasma will be screened for specific anti-tumor immunoglobulins at diagnosis and at key treatment time points. In the meanwhile, levels of circulating cytokines concentrations will be evaluated by Luminex, especially those known to have inhibitory effects on immune effectors: IL-4, IL-5, IL-6, IL-10, TGF-beta, HLA-Gs, TNF-alpha, IFN-gama, IL-2, IL-12, IL-27, IL-17 and CD40L (already in place).

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age <= 21 years
  • Patient with neuroblastoma any stage, in the first line or relapsed, or suspicion of neuroblastoma
  • Covered by a medical insurance
  • Written, signed informed consent (patient, and parents if minor child)

Exclusion Criteria:

  • Patients who received corticosteroids within 15 days prior to sampling
  • Patients receiving immunosuppressive therapy
  • Chemotherapy before sampling began
  • Neuroblastoma in a genetic syndrome predisposing
  • Deterioration of clinical status
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01295762

Contacts
Contact: David PEROL, MD +33 4 78 78 27 52 david.perol@lyon.unicancer.fr
Contact: Séverine GUILLEMAUT +33 4 78 78 29 68 severine.guillemaut@lyon.unicancer.fr

Locations
France
Hopital D'Estaing Active, not recruiting
Clermont Ferrand, France, 63100
Chu Grenoble - Hopital Nord Recruiting
La Tronche, France, 38700
Contact: Dominique PLANTAZ, MD       DPlantaz@chu-grenoble.fr   
Sub-Investigator: Anne PAGNIER, MD         
Sub-Investigator: Corinne ARMARI-ALLA, MD         
Principal Investigator: Dominique PLANTAZ, MD         
IHOP Recruiting
Lyon, France, 69008
Contact: Aurélien MARABELLE, MD       MARABELL@lyon.fnclc.fr   
Sub-Investigator: Christophe BERGERON, MD         
Principal Investigator: Aurélien MARABELLE, MD         
Chu - Hopital Nord Recruiting
Saint Priest En Jarez, France, 42270
Contact: Jean-Louis STEPHAN, MD       j.louis.stephan@chu-st-etienne.fr   
Sub-Investigator: Claire BERGER, MD         
Sub-Investigator: Sandrine THOUVENIN-DOULET, MD         
Principal Investigator: Jean Louis STEPHAN, MD         
Sponsors and Collaborators
Centre Leon Berard
Investigators
Principal Investigator: Aurélien MARABELLE, MD IHOP
  More Information

Publications:

Responsible Party: Centre Leon Berard
ClinicalTrials.gov Identifier: NCT01295762     History of Changes
Other Study ID Numbers: IMMUNEURO
Study First Received: February 11, 2011
Last Updated: January 30, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Centre Leon Berard:
Children
Cancer
Immunomonitoring
Prognostic/Predictive Factors
Immunotherapy

Additional relevant MeSH terms:
Neuroblastoma
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue

ClinicalTrials.gov processed this record on April 17, 2014