Hematological Anomalies in Children With Rasopathy

Recruiting

• Conditions: RAS Mutation

• Registration Number: NCT04286360
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-01-17
• Study First Submitted QC: 2020-02-24
• Study First Posted: 2020-02-27
• Study Start: 2020-11-11
• Status Verified: 2024-05
• Last Update Submitted: 2024-06-03
• Last Update Posted: 2024-06-04
• Primary Completion: 2025-05
• Study Completion: 2029-11

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 300

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Proportion of patients with hematological abnormalities	at inclusion (within 6 months after diagnosis)

Secondary Outcome Measures

Name	Time	Method
Event-free survival	at 5 years post-inclusion
Proportion of patients with hematological abnormalities according to genetic abnormality	at inclusion (within 6 months after diagnosis)
Proportion of patients with hematological abnormalities according to genetic abnormalities	at 1 year after inclusion
Proportion of patients with hematological abnormalities	at 1 year after inclusion
Proportion of patients with hematological abnormalities according to age	at 1 year after inclusion
Evolution of proportion of patients with hematological abnormalities during childhood	at 5 years post-inclusion

Trial Locations

Locations (13)

CHU Caen; 🇫🇷 Caen, France

CHU Angers; 🇫🇷 Angers, France

CHU Lille; 🇫🇷 Lille, France

CHU Lyon; 🇫🇷 Lyon, France

Hôpital Robert Debré APHP; 🇫🇷 Paris, France

CHU Marseille - Hôpital de la Timone; 🇫🇷 Marseille, France

CHU Montpellier; 🇫🇷 Montpellier, France

Hôpital Necker APHP; 🇫🇷 Paris, France

CHU Nantes; 🇫🇷 Nantes, France

Hôpital Trousseau APHP; 🇫🇷 Paris, France

CHU Rennes; 🇫🇷 Rennes, France

CHU Strasbourg; 🇫🇷 Strasbourg, France

CHU Toulouse; 🇫🇷 Toulouse, France