Immunomonitoring of Children With Neuroblastoma (Immuneuro)

August 22, 2018 updated by: Centre Leon Berard

Immunomonitoring of Children With Neuroblastoma for the Development of Antitumor Immunotherapy Strategies

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Actual)

35

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Clermont Ferrand, France, 63100
        • Hôpital d'Estaing
      • La Tronche, France, 38700
        • Chu Grenoble - Hopital Nord
      • Lyon, France, 69008
        • IHOP
      • Saint Priest En Jarez, France, 42270
        • Chu - Hopital Nord

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Screening
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: 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 Names:
  • No intervention other names

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Description of immune effectors in the blood, marrow and tumor diagnosis.
Time Frame: 1 year
Rate effectors immunitaires in blood, marrow and tumor present at diagnosis
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre Leon Berard

Investigators

  • Principal Investigator: Aurélien MARABELLE, MD, IHOP

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2011

Primary Completion (Anticipated)

March 1, 2019

Study Completion (Anticipated)

July 1, 2019

Study Registration Dates

First Submitted

February 11, 2011

First Submitted That Met QC Criteria

February 11, 2011

First Posted (Estimate)

February 14, 2011

Study Record Updates

Last Update Posted (Actual)

August 23, 2018

Last Update Submitted That Met QC Criteria

August 22, 2018

Last Verified

August 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IMMUNEURO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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