NeuroblastomaImmuneuroNCT01295762
Immunomonitoring of Children With Neuroblastoma
A study testing Immunological analyses in people with Neuroblastoma, run by Centre Leon Berard at 4 sites in France.
Trial summary
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… Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Neuroblastoma
- What is being tested?
- Immunological analyses
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 4 sitesFrance
- Study dates
- May 2011to Jul 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
4 sites in 1 country.
France4 sites
Hopital D'Estaing
Clermont-Ferrand, 63100
Chu Grenoble - Hopital Nord
La Tronche, 38700
IHOP
Lyon, 69008
Chu - Hopital Nord
Saint-Priest-en-Jarez, 42270
About this study
Official title: 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.
Read more
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.
Read the 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).
- Conditions
- Neuroblastoma
- Being tested
- Immunological analyses
- Keywords
- Children, Cancer, Immunomonitoring, Prognostic/Predictive Factors, Immunotherapy
- Medical subject headings
- Neuroblastoma, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Immunological analysesOther
Also called No intervention other names
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 group | Role | What they receive |
|---|---|---|
| Type of neuroblastoma | Other | Neonatal stages I Localized immediately resectable stages Localized immediately unresectable stages High-risk neuroblastoma Relapsed neuroblastoma Receives: Other: Immunological analyses |
What is being measured
The primary outcome is the main question the study is designed to answer.
Description of immune effectors in the blood, marrow and tumor diagnosis.
Rate effectors immunitaires in blood, marrow and tumor present at diagnosis
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Feb 2011 (estimated)
- Study startMay 2011
- Primary completionMar 2019 (estimated)
- Study completionJul 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for NeuroblastomaStudies of the same condition, open and under way.
- More trials run by Centre Leon BerardThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Screening
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Leon Berard
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Aurélien MARABELLE, MD, Principal investigator, IHOP
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01295762
- Sponsor's protocol ID
- IMMUNEURO
- Acronym
- Immuneuro
- Status last verified
- Aug 2018
- First submitted
- 11 Feb 2011
- Last updated
- 23 Aug 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
Marabelle A, Merlin E, Halle P, Paillard C, Berger M, Tchirkov A, Rousseau R, Leverger G, Piguet C, Stephan JL, Demeocq F, Kanold J. CD34+ immunoselection of autologous grafts for the treatment of high-risk neuroblastoma. Pediatr Blood Cancer. 2011 Jan;56(1):134-42. doi: 10.1002/pbc.22840.
PubMed 21058288Bertrand A, Marec-Berard P, Raverot G, Trouillas J, Marabelle A. Cabergoline therapy of paraneoplastic Cushing syndrome in children. Pediatr Blood Cancer. 2010 Sep;55(3):589-90. doi: 10.1002/pbc.22581. No abstract available.
PubMed 20658641Marabelle A, Bergeron C, Billaud G, Mekki Y, Girard S. Hemophagocytic syndrome revealing primary HHV-6 infection. J Pediatr. 2010 Sep;157(3):511. doi: 10.1016/j.jpeds.2010.02.064. Epub 2010 Apr 18. No abstract available.
PubMed 20400100Marabelle A, Sapin V, Rousseau R, Periquet B, Demeocq F, Kanold J. Hypercalcemia and 13-cis-retinoic acid in post-consolidation therapy of neuroblastoma. Pediatr Blood Cancer. 2009 Feb;52(2):280-3. doi: 10.1002/pbc.21768.
PubMed 18839433Marabelle A, Campagne D, Dechelotte P, Chipponi J, Demeocq F, Kanold J. Focal nodular hyperplasia of the liver in patients previously treated for pediatric neoplastic diseases. J Pediatr Hematol Oncol. 2008 Jul;30(7):546-9. doi: 10.1097/MPH.0b013e3181691709.
PubMed 18797204Kanold J, Paillard C, Tchirkov A, Merlin E, Marabelle A, Lutz P, Rousseau R, Baldomero H, Demeocq F. Allogeneic or haploidentical HSCT for refractory or relapsed solid tumors in children: toward a neuroblastoma model. Bone Marrow Transplant. 2008 Oct;42 Suppl 2:S25-30. doi: 10.1038/bmt.2008.279.
PubMed 18978740Kanold J, Merlin E, Halle P, Paillard C, Marabelle A, Rapatel C, Evrard B, Berger C, Stephan JL, Galambrun C, Piguet C, D'Incan M, Bordigoni P, Demeocq F. Photopheresis in pediatric graft-versus-host disease after allogeneic marrow transplantation: clinical practice guidelines based on field experience and review of the literature. Transfusion. 2007 Dec;47(12):2276-89. doi: 10.1111/j.1537-2995.2007.01469.x. Epub 2007 Aug 30.
PubMed 17764513
Study at a glance
From the registry record, last updated by the sponsor on 23 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immunomonitoring of Children With Neuroblastoma for the Development of Antitumor Immunotherapy Strategies
- ClinicalTrials.gov ID
- NCT01295762
- Acronym / sponsor ID
- Immuneuro / IMMUNEURO
- Conditions
- Neuroblastoma
- Keywords
- Children, Cancer, Immunomonitoring, Prognostic/Predictive Factors, Immunotherapy
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Centre Leon BerardUniversity, hospital or other
- Study start
- May 2011 (actual)
- Primary completion
- Mar 2019 (estimated)
- Study completion
- Jul 2019 (estimated)
- First posted
- 14 Feb 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Screening
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Type of neuroblastoma | Other | Other: Immunological analysesNeonatal stages I Localized immediately resectable stages Localized immediately unresectable stages High-risk neuroblastoma Relapsed neuroblastoma |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- 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)
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Immunological analysesAlso: No intervention other namesImmunological 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 | Type of neuroblastoma |
Primary outcome
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Aug 2018.
- Results publication: PubMed 21058288Marabelle A, Merlin E, Halle P, Paillard C, Berger M, Tchirkov A, Rousseau R, Leverger G, Piguet C, Stephan JL, Demeocq F, Kanold J. CD34+ immunoselection of autologous grafts for the treatment of high-risk neuroblastoma. Pediatr Blood Cancer. 2011 Jan;56(1):134-42. doi: 10.1002/pbc.22840.
- Results publication: PubMed 20658641Bertrand A, Marec-Berard P, Raverot G, Trouillas J, Marabelle A. Cabergoline therapy of paraneoplastic Cushing syndrome in children. Pediatr Blood Cancer. 2010 Sep;55(3):589-90. doi: 10.1002/pbc.22581. No abstract available.
- Results publication: PubMed 20400100Marabelle A, Bergeron C, Billaud G, Mekki Y, Girard S. Hemophagocytic syndrome revealing primary HHV-6 infection. J Pediatr. 2010 Sep;157(3):511. doi: 10.1016/j.jpeds.2010.02.064. Epub 2010 Apr 18. No abstract available.
- Results publication: PubMed 18839433Marabelle A, Sapin V, Rousseau R, Periquet B, Demeocq F, Kanold J. Hypercalcemia and 13-cis-retinoic acid in post-consolidation therapy of neuroblastoma. Pediatr Blood Cancer. 2009 Feb;52(2):280-3. doi: 10.1002/pbc.21768.
- Results publication: PubMed 18797204Marabelle A, Campagne D, Dechelotte P, Chipponi J, Demeocq F, Kanold J. Focal nodular hyperplasia of the liver in patients previously treated for pediatric neoplastic diseases. J Pediatr Hematol Oncol. 2008 Jul;30(7):546-9. doi: 10.1097/MPH.0b013e3181691709.
- Results publication: PubMed 18978740Kanold J, Paillard C, Tchirkov A, Merlin E, Marabelle A, Lutz P, Rousseau R, Baldomero H, Demeocq F. Allogeneic or haploidentical HSCT for refractory or relapsed solid tumors in children: toward a neuroblastoma model. Bone Marrow Transplant. 2008 Oct;42 Suppl 2:S25-30. doi: 10.1038/bmt.2008.279.
- Results publication: PubMed 17764513Kanold J, Merlin E, Halle P, Paillard C, Marabelle A, Rapatel C, Evrard B, Berger C, Stephan JL, Galambrun C, Piguet C, D'Incan M, Bordigoni P, Demeocq F. Photopheresis in pediatric graft-versus-host disease after allogeneic marrow transplantation: clinical practice guidelines based on field experience and review of the literature. Transfusion. 2007 Dec;47(12):2276-89. doi: 10.1111/j.1537-2995.2007.01469.x. Epub 2007 Aug 30.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Aurélien MARABELLE, MD principal investigator
IHOP
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Immunological analyses in people with Neuroblastoma, run by Centre Leon Berard at 4 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Description of immune effectors in the blood, marrow and tumor diagnosis. (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01295762, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Aug 2018.