Immunodeficiency and Cancer: Identification of Congenital Immune System Defects Underlying Paediatric Lymphomas

Immune Deficiency Clinical Trial

Official title:

Immunodeficiency and Cancer: Identification of Congenital Immune System Defects Underlying Paediatric Lymphomas

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06332196
• Other study ID #: L-IEI
• Status: Recruiting
• Phase: N/A
• Start date: October 18, 2023
• Est. completion date: October 18, 2025

Study information

• Verified date: March 2024
• Source: Meyer Children's Hospital IRCCS
• Contact: Eleonora Gambineri
• Phone: 0555662624
• Email: eleonora.gambineri[@]meyer.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Inborn Errors of Immunity (IEI) are a heterogeneous group of disorders characterised not only by an infectious diathesis, but by a wide variety of other clinical manifestations. Lymphoma is one of the most common malignancies in children and may be the first clinical manifestation of IEI, thereby 'hiding' the immune defect and delaying genetic/immunological diagnosis. Lymphomas, especially non-Hodgkin's lymphomas (NHL) are frequently associated with congenital defects of the immune system, in particular diffuse large B-cell lymphoma and Burkitt's lymphoma. Preliminary analyses conducted on 6 patients diagnosed with NHL allowed the identification of genetic variants in genes associated with IEI. In clinical practice, the diagnosis and choice of therapeutic treatment in patients with immunodeficiency-associated lymphoma are decisive and, due to the complex pathophysiology of the disease, it is not always possible to identify the boundary between benign and malignant proliferation. The identification of an undiagnosed immunodeficiency in patients with lymphoma will ensure the opportunity to apply targeted therapies, such as allogeneic haematopoietic stem cell transplantation, instead of standard clinical management based mainly on chemotherapy. The study aims to identify possible congenital defects of immunity, i.e. genetic disorders affecting the immune system, as responsible for the development of haematological malignancies. Through a multidisciplinary approach involving immunological analyses, genetic analyses and a thorough examination of clinical manifestations, we aim to characterise the immunological component underlying the development of paediatric lymphomas.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: October 18, 2025
• Est. primary completion date: June 18, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Day to 24 Years

Eligibility

Inclusion Criteria:

• Patients with a clinical diagnosis of Hodgkin's lymphoma (HL) or non-Hodgkin's lymphoma (NEIL) with or without signs of immune dysregulation (lymphoproliferation, autoimmunity, hypogammaglobulinaemia, family history of immunodeficiency).
• Patients with previous HL or NEIL lymphoma who have developed, concomitantly with the tumour or subsequently, clinical manifestations mentioned above attributable to a congenital defect of immunity.

Exclusion Criteria:

• Patients with known genetic diseases, or who do not consent to participate in the study

Related Conditions & MeSH terms

• Immune Deficiency
• Immunologic Deficiency Syndromes

Intervention

Other:
• Analysis of biological sample and clinical data
Analysis of biological sample and clinical data

Locations

Country	Name	City	State
Italy	AOU Malpighi IRCCS	Bologna
Italy	Meyer Children's Hospital IRCCS	Florence
Italy	AOU Pisana	Pisa
Italy	Ospedale Pediatrico Bambin Gesù IRCCS	Roma

Sponsors (1)

Lead Sponsor	Collaborator
Meyer Children's Hospital IRCCS

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To unravel inborn error of immunity behind Lymphoid neoplasm in children	Characterizing the role of the immune system in the pathogenesis of polyclonal and clonal lymphoproliferation. In particular, the main aim of our study will be the identification, by means of second-generation genetic analysis and functional validation studies of the identified variants, of congenital immune system defects in patients with lymphoid neoplasia	Through study completion, an average of 1 year
Secondary	Identification of lymphoma-specific biomarkers	Investigating Cell-Free DNA for specific molecular alterations in lymphomas, in order to monitor the follow-up of patients affected by lymphoma and to identify early onset of clonality in patients with already diagnosed congenital defects of the immune system at risk of developing malignant lymphoproliferation.	Through study completion, an average of 1 year