Clinical trial NCT04286360: Hematological Anomalies in Children With Rasopathy
Official title: Hematological Anomalies in Children With Rasopathy
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: RAS Mutation
Keywords: RASopathie
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2020-02-27
Enrollment: 300
Sex: ALL
Maximum age (years): 15
Standard ages: CHILD
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients aged 15 years old and younger with RASopathies (Noonan syndrome and related diseases)

Brief summary: During childhood, patients with RASopathies (Noonan syndrome and related diseases) can harbor various hematological anomalies ranging from isolated monocytosis, myelemia, thrombocytopenia or splenomegaly to myeloproliferative disorders. These anomalies may spontaneously disappear or persist, sometimes leading to juvenile myelomonocytic leukemia. Guidelines for initial screening and subsequent hematological follow-up have recently been published in France: peripheral blood analysis should be performed in all newly diagnosed patients and followed by biannual peripheral blood analysis in infants until the age of 2 years.

In order to describe the characteristics of these abnormalities in terms of their incidence, age of occurrence, evolution and relation to genotype, we are conducting a longitudinal prospective study whose aim is to analyze peripheral blood cell counts and smears at diagnosis and one year later. In patients \<3 years of age recruited at certain centers, biobanking of mononuclear cells will be performed. These data could yield a new insight into hematological anomalies in patients with RASopathies and thereby help physicians to determine the appropriate rhythm for hematological follow-up according to genotype.


Eligibility criteria: Inclusion Criteria:

* Age \< 16 years
* Patient newly diagnosed with genetically confirmed rasopathy : Noonan syndrome, type 1 neurofibromatosis, Noonan syndrome with multiple lentigines, CBL syndrome, Costello syndrome, cardiofaciocutaneous syndrome or Legius syndrome i.e. with a germline mutation of one of these genes: PTPN11, SOS1, NRAS, RAF1, BRAF, SHOC2, MEK1, MEK2, CBL, NF1, SPRED1, KRAS, HRAS, NF1, SHOC2, LZTR1, SOS2, RIT1, RASA2, RRAS, PPP1CB, or a new gene of interest published during the recruitment period
* No history of hematological malignancy
* Written informed consent obtained from the parents
* Health insurance

Exclusion Criteria:

* History of malignant hematological pathology

Primary outcomes:
measure: Proportion of patients with hematological abnormalities
timeFrame: at inclusion (within 6 months after diagnosis)
Secondary outcomes:
measure: Proportion of patients with hematological abnormalities according to genetic abnormality
timeFrame: at inclusion (within 6 months after diagnosis)
measure: Proportion of patients with hematological abnormalities according to age
timeFrame: at inclusion (within 6 months after diagnosis)
measure: Proportion of patients with hematological abnormalities
timeFrame: at 1 year after inclusion
measure: Proportion of patients with hematological abnormalities according to age
timeFrame: at 1 year after inclusion
measure: Proportion of patients with hematological abnormalities according to genetic abnormalities
timeFrame: at 1 year after inclusion
measure: Evolution of proportion of patients with hematological abnormalities during childhood
timeFrame: at 5 years post-inclusion
measure: Event-free survival
timeFrame: at one year post-inclusion
measure: Event-free survival
timeFrame: at 5 years post-inclusion
Other outcomes:
Locations:
city: Angers
country: France
facility: CHU Angers
city: Caen
country: France
facility: CHU Caen
city: Lille
country: France
facility: CHU Lille
city: Lyon
country: France
facility: CHU Lyon
city: Marseille
country: France
facility: CHU Marseille - Hôpital de la Timone
city: Montpellier
country: France
facility: CHU Montpellier
city: Nantes
country: France
facility: CHU Nantes
city: Paris
country: France
facility: Hôpital Necker APHP
city: Paris
country: France
facility: Hôpital Robert Debré APHP
city: Paris
country: France
facility: Hôpital Robert Debré APHP
city: Paris
country: France
facility: Hôpital Trousseau APHP
city: Rennes
country: France
facility: CHU Rennes
city: Strasbourg
country: France
facility: CHU Strasbourg
city: Toulouse
country: France
facility: CHU Toulouse
Study officials:
References: