The Interplay Between Inborn Error of Immunity and Blood Disorders: Unravelling Immune Defects Behind Common Haematological Diseases

NCT ID: NCT06857604

Last Updated: 2025-03-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

700 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-11-15

Study Completion Date

2027-07-31

Brief Summary

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The universe of Inborn errors of Immunity (IEI) is rapidly expanding: their clinical spectrum is not only characterised by infections but often includes haematological complications. Moreover, an increasing number of "IEI phenocopies" due to somatic mutations in specific cell types are progressively being unveiled and complicate the genetic plot of IEI, which are therefore not only caused by germline mutations. However, these aspects have never been studied by large prospective studies.

This study aims to fill this gap by prospectively recruiting patients \<25 y/o with haematologic disorders that fall into one of the following 4 subgroups: autoimmune cytopenia (AICs), polyclonal lymphoproliferation (PL), monoclonal (malignant) lymphoproliferation (ML), bone marrow failure/myelodysplasia (BMF/MDS). Recruited subjects will undergo an extensive immunologic workup (extended immunophenotyping, cytokine and autoantibody dosage) together with genetic testing (NGS) to detect both germline and somatic variants. Bulk RNA sequencing will be performed either as functional validation of variants or to identify altered pathways in selected cases with inconclusive genetics. Patient advocacy organisations (PAOs) will be pivotal to assist patients' needs throughout the project and to raise awareness of predictive and yet unknown signs of IEI.

The study involves recruitment a total of almost 700 children over a 3-year period. Considering recent studies on AICs and BMF/MDS, a global detection rate of 30% "hidden" IEI is expected, with higher rates in the AIC subgroup and lower ones for ML, given the complexity of lymphoma pathogenesis. New IEI candidate genes or new examples of IEI phenocopies are expected to be identified.

The immunological workup should detect early disease biomarkers or currently unknown molecular signatures of specific disorders. These may increase the chance of identifying an IEI in a specific subgroup and promptly address the patient to a targeted treatment or to hematopoietic stem cell transplantation, avoiding late complications, increasing patients' survival, and abating the economic burden of the disease on healthcare services. Finally, involvement of PAOs may foster patients' knowledge about their condition, increasing their compliance to disease follow-up and treatment and ameliorating their quality of life.

Detailed Description

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Conditions

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Hematologic Diseases

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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Patients with Haematological Disorders

Patients with diagnosed autoimmune cytopenias (AIC), polyclonal lymphoproliferation (PL), lymphoma (ML), bone marrow failure, and myelodysplastic syndrome (BMF/MDS)

Group Type OTHER

Biological samples

Intervention Type OTHER

Immunological Screening and Genetic analysis

Interventions

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Biological samples

Immunological Screening and Genetic analysis

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. Patients age \< 25 years
2. Patients with diagnosed autoimmune cytopenias (AIC), polyclonal lymphoproliferation (PL), lymphoma (ML), bone marrow failure, and myelodysplastic syndrome (BMF/MDS) (see details below)
3. Signed Informed Consent

Exclusion Criteria

1. Patients with Lymphoma secondary to HIV or transplant
2. Patient with self-resolving or post-infective AICs
Maximum Eligible Age

25 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Meyer Children's Hospital IRCCS

OTHER

Sponsor Role lead

Responsible Party

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Eleonora Gambineri

Medical Doctor

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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CHU Sainte-Justine

Montreal, Canada, Canada

Site Status RECRUITING

CHU Sainte-Justine

Montreal, Canada, Canada

Site Status RECRUITING

Institut Imagine

Paris, France, France

Site Status RECRUITING

Meyer Children's Hospital IRCCS, Firenze

Florence, Fi, Italy

Site Status RECRUITING

University of Rome Tor Vergata

Rome, Italy, Italy

Site Status RECRUITING

Vall d'Hebron Institut de Recerca

Barcelona, , Spain

Site Status RECRUITING

Karolinska Institutet

Stockholm, Sweden, Sweden

Site Status RECRUITING

Countries

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Canada France Italy Spain Sweden

Central Contacts

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Eleonora Gambineri, MD

Role: CONTACT

+390555662624

Facility Contacts

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Elie Haddad

Role: primary

Vincent-Philippe Lavallee

Role: primary

Frederic Rieux-Laucat

Role: primary

Gambineri

Role: primary

+390555662624

Maria Teresa Voso

Role: primary

Pere Soler Palacin

Role: primary

Qiang Pan-Hammarström

Role: primary

Other Identifiers

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IEI-Haem

Identifier Type: -

Identifier Source: org_study_id

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