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Biological Characterisation of High Risk CHildhood Cancer in Children, Adolescents and Young Adults (MICCHADO)

Not Applicable
Active, not recruiting
Conditions
Ewing Sarcoma Family of Tumors
Rhabdomyosarcoma
Central Nervous System Tumor
Leukemia
Neuroblastoma
Osteosarcoma
Interventions
Other: Sampling on blood, bone marrow and cerebrospinal fluid
Registration Number
NCT03496402
Lead Sponsor
Institut Curie
Brief Summary

Methodology:

Prospective, multicentric, open, non-randomised, non-therapeutic, interventional study

Detailed Description

To identify and characterise:

* meaningful molecular genetic alterations,

* meaningful immunological features of high risk childhood, adolescents and young adult cancers, at diagnosis, during patient treatment and follow-up (time dimension).

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
600
Inclusion Criteria
  1. Inclusion within 3 months after diagnosis

  2. Availability of a cryopreserved tumour sample (primary and/or metastatic and/or lymph nodes) or peripheral blood or bone marrow samples (if invasion more than 30% of lymphoblasts) for leukaemias, obtained at the time of diagnosis during a routine procedure

  3. Availability of a formalin-fixed paraffin-embedded (FFPE) tumour sample (primary and/or metastasis and/or lymph nodes), obtained at the time of diagnosis during a routine procedure (except for leukaemia patients)

  4. Age: ≤ 25 years at diagnosis

  5. Written patient informed consent, or parents or legal representative written informed consent and assent of the child and the adolescent

  6. Compulsory affiliation to a social security scheme

    Additional inclusion criteria for the study:

    To avoid multiple sampling for children, adolescents and young adults with cancer, patients already included or to be included in a study with similar analyses and/or objectives might also be included in MICCHADO study and in this case, samples or data might be exchanged on a collaborative basis.

    Cohort 1:

    • High risk neuroblastoma:

      • Any type of neuroblastoma with MYCN amplification, except INSS stage 1

      • Stage 4 neuroblastoma in children older than one year at diagnosis

    • High risk rhabdomyosarcoma:

      • Foxo1 rearrangement any stage;
      • and / or N1 ;
      • and / or metastatic rhabdomyosarcoma
    • High risk Ewing sarcoma:

      • Metastatic Ewing sarcoma family of tumours (ESFT)
      • Localised inoperable Ewing sarcoma with primary tumours ≥ 200 ml
    • High risk osteosarcoma:

      • Metastatic osteosarcoma

      • Localised inoperable osteosarcoma

    • High risk leukaemia:

      • Secondary acute myeloid leukaemia
      • Biphenotypic acute leukaemia

    Cohort 2:

    • Extra cerebral or cerebral high risk tumours including:

    • other metastatic sarcomas,
    • other rare high risk cancers,
    • high risk renal tumours with surgery after an initial chemotherapy
    • rhabdoid brain tumours (AT/RT) and extra cerebral rhabdoid tumours
    • high risk or metastatic cancers of unclear histological diagnosis • Lymphoblastic leukaemia with high MRD at Day 78 (time point 2) • Very high risk T-cells acute lymphoblastic leukaemia:
    • MRD ≥ 10-2 at the end of the induction ;
    • or MRD ≥ 10-3 at Day 78

    Cohort 3:

    Children, adolescents and young adults, with low/intermediate risk cancers belonging to the following types:

    • Neuroblastoma:

    • Localised, without MYCN amplification
    • Localised, INSS stage 1, with MYCN amplification

    • Stage 4s, in infants (younger than one year at diagnosis), without MYCN amplification

      • Rhabdomyosarcoma:

    • Localised, without Foxo1 rearrangement

      • ESFT:

    • All non-high risk localised ESFT • Osteosarcoma:

    • All non-high risk localised osteosarcoma

Exclusion Criteria

Main non-inclusion Criteria common to all study cohorts:

  1. Age: patients > 25 years old at diagnosis 2) Absence of patient or parents or legal representative written informed consent 3) Patient for whom follow-up by the investigating centre does not appear feasible

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
High risk CohortsSampling on blood, bone marrow and cerebrospinal fluidCohort 1 : High risk Neuroblastoma, High risk Rhabdomyosarcoma, High risk Ewing Sarcoma Family Tumor, High risk Osteosarcoma, High risk Leukaemia (secondary acute myeloid leukaemia or biphenotypic acute leukaemia) Cohort 2 : Extracerebral and cerebral high risk tumor, High risk Leukaemia (leukaemia with high MRD) Sampling on blood, bone marrow and cerebrospinal fluid
Low risk CohortSampling on blood, bone marrow and cerebrospinal fluidCohort 3 : Intermediate or low risk tumors : Neuroblastoma, Rhabdomyosarcoma, Ewing Sarcoma Family Tumor, Osteosarcoma Sampling on blood, bone marrow and cerebrospinal fluid
Primary Outcome Measures
NameTimeMethod
Number of patients with meaningful immunological featuresAt the end of study (6 years)

Identification and characterisation of the tumor microenvironment and the host's immunological profile, at diagnosis and during patient treatment

Number of patients with meaningful molecular genetic alterationsAt the end of study (6 years)

Identification of molecular genetic alterations based on molecular characterisation of tumor at diagnosis, during patient treatment and follow-up (time dimension)

Number of patients with identification of new tumor-specific genetic characteristics during follow-up (clonal evolution)up to 6 years

Comparison between genetic variations identified at diagnosis and those identified on circulating tumor DNA during treatment, FU and/or relapse

Secondary Outcome Measures
NameTimeMethod
Correlation between disease staging and immunological featuresup to 6 years

To investigate the impact of the tumour microenvironment and host's immunological profile on the disease staging at diagnosis, by comparing patients with metastatic to patients with localised disease

Correlation between genetic variations and immune parametersup to 6 years

To compare molecular and immunological findings at diagnosis and during treatment (data integration)

Correlation between disease recurrence and molecular and/or immunological biomarkersup to 6 years

To characterise biomarkers, based on molecular analyses of tumour samples from diagnosis, for prognostic and predictive purposes.

To characterise the tumour microenvironment and the host's immunological profile, for prognostic and predictive purposes.

To identify potential prognostic and predictive biomarkers on samples collected during patient's treatment and follow-up, based on changes on circulating tumour DNA (ctDNA), detected by molecular biology techniques, and on immunological findings

Trial Locations

Locations (30)

Hôpital d'Enfants Armand-Trousseau

🇫🇷

Paris, France

Hôpital universitaire Robert-Debré (AP-HP)

🇫🇷

Paris, France

Hôpital l'Archet 2

🇫🇷

Nice, France

Chu D'Amiens Picardie

🇫🇷

Amiens, France

CHU Angers

🇫🇷

Angers, France

CHRU de Besançon - Hôpital Jean-Minjoz

🇫🇷

Besançon, France

CHU de Bordeaux - Hôpital des enfants - Groupe Hospitalier Pellegrin

🇫🇷

Bordeaux, France

CHRU de Brest

🇫🇷

Brest, France

CHU CAEN

🇫🇷

Caen, France

Centre Régional de Cancérologie et Thrapie Cellulaire Pdiatrique (CRCTCP)

🇫🇷

Clermont-Ferrand, France

CHU Hôpital d'Enfants

🇫🇷

Dijon, France

CHU GRENOBLE Alpes - Hôpital Couple-Enfant

🇫🇷

Grenoble, France

Centre Oscar Lambret

🇫🇷

Lille, France

CHU de Limoges - Hôpital Mère-Enfant

🇫🇷

Limoges, France

Centre Léon Bérard

🇫🇷

Lyon, France

Hospices Civils de Lyon

🇫🇷

Lyon, France

Hôpital d'Enfants de la Timone (AP-HM)

🇫🇷

Marseille, France

CHU Arnaud de Villeneuve

🇫🇷

Montpellier, France

CHU Nantes - Hôpital Mère Enfant

🇫🇷

Nantes, France

Institut Curie

🇫🇷

Paris, France

CHU de Poitiers

🇫🇷

Poitiers, France

CHU de Reims - Hôpital Américain

🇫🇷

Reims, France

Chu Hopital Sud Rennes

🇫🇷

Rennes, France

CHU de Rouen - Hôp. Charles NICOLLE

🇫🇷

Rouen, France

CHU Saint-Etienne - Hôpital Nord

🇫🇷

Saint-Étienne, France

Hôpitaux Universitaires de Strasbourg - Hôpital de Hautepierre

🇫🇷

Strasbourg, France

CHU Hôpital des Enfants

🇫🇷

Toulouse, France

CHU TOURS - Hôpital Clocheville

🇫🇷

Tours, France

CHU Nancy - Hôpital d'Enfants

🇫🇷

Vandoeuvre les Nancy, France

Gustave Roussy

🇫🇷

Villejuif, France

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