An interventional study of Genetic profiling of all eligible patients in Lymphatic Malformation, Lymphatic Abnormality and Lymphangioma, sponsored by Fondazione Policlinico Universitario Agostino Gemelli IRCCS. Recruiting at 1 site in Italy. Open to participants aged Up to 100 Years. Per ClinicalTrials.gov, last updated 2025-03-25.
Sponsored by Fondazione Policlinico Universitario Agostino Gemelli IRCCS · Not applicable, Interventional, and Other
Lymphatic malformations (ML), are benign non-neoplastic, rare, resulting from an embryologic abnormal development of the lymphatic system. Sometimes they may be associated with other vascular malformations (venous or arterial)1,2. ML usually appear at birth, in early childhood or during the first years of life (congenital vs. acquired) and are mainly localized in the region of the head and neck, armpits, groin, retroperitoneal tissues, tongue and mucous membranes of the oral cavity since these areas contain a plethora of lymphatic structures1. The main complications due to their location are airway obstruction, difficulty in eating, and bleeding3-5. Infection and bleeding can promote the sudden, progressive and accelerated growth of these lesions1. The location, speed of growth, and the subsequent complications associated with ML, determine the overall severity of the clinical picture and require generally the referral of the affected patient to a specialized center that can ensure a multidisciplinary care3,5. Recently, the International Society for the Study of Vascular Anomalies (ISSVA), has revised and updated the classification of such malformations, emphasizing the distinction between isolated forms and ML in the context of more complex syndromes with multisystem involvement2. Until a few years ago, the only treatment strategies available for ML were scleroembolization, cryotherapy, transcutaneous laser photocoagulation, and surgical resection of the malformation. The recent identification of genetic alterations in the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/target mammalian pathway of rapamycin (mTOR), which underlies many isolated and syndromic ML pictures6-9, has opened up important prospects for personalized treatment with repurposed drugs6,7,10-20. Over the years, the rarity and complexity of ML management have resulted in a fragmented nature of available information and poor nationwide sharing of diagnostic-clinical-assistance-therapeutic protocols (PDTAs) with the consequent need for many families to undertake multispecialty consultations in various provinces or regions before identifying a suitable Referral Center. In addition, recent acquisitions in genetics have forced specialists, a further reevaluation of those complex clinical pictures of ML, whether isolated or syndromic, that could be candidates for personalized drug treatments.
The institution of a national Registry of pathology promoted by the Association of Patients with Lymphatic Malformations, which supports clinicians and families in filling unmet information and clinical care gaps, is a priority project in order to improve the quality of life of patients and the level of care offered to them. In addition, the establishment of a collection of biological specimens, processed according to high quality standards, within a Research Biobank provides the opportunity for patients and their families to maximize the visibility of the specimens, promoting their use in national and international research projects dedicated to ML, in compliance with ELSI (Ethical, Social, and Legal Issues) criteria.
The study primary Objective is To create a computerized registry for ML that collects both retrospective and prospective data in order to estimate the incidence and prevalence of ML, in different phenotypes.
As secondary objectives. (i) Establish a collection of biological specimens (Fresh and fixed biopsy tissue; DNA extracted from whole blood, saliva and where possible from biopsy tissue) within the FPG Research Biobank, intended for future research purposes and available to the entire scientific community; ii) Genetically profile patients who have never undergone molecular diagnostics or who have been tested with restricted panels of genes (PIK3CA, AKT, MTOR, PTEN, KRAS and BRAF) (activity performed on patients per clinical practice); (iii) Define the natural history of ML in different phenotypes and genotypes from prenatal to adult age; (iv) Evaluate the clinical outcomes of different treatments (e.g., experimental drug therapy, maxillofacial surgery, vascular surgery, laser therapy, sclerotherapy, compression therapy, etc.) and different modes of care (type and frequency of visits performed) in the short and long term; (v) Assess the impact of ML on the lives of patients and caregivers; (vi) Support the drafting/updating of national recommendations and standards of care; vii) to promote and facilitate the implementation of research projects dedicated to ML, fostering the advancement of scientific knowledge on this specific disease area;
ENDPOINT Primary endpoint
References:
Ozeki M, Nozawa A, Yasue S, et al. The impact of sirolimus therapy on lesion size, clinical
symptoms, and quality of life of patients with lymphatic anomalies. Orphanet J Rare Dis. 2019;14(1):141. doi:10.1186/s13023-019-1118-1
42 studies on the registry are indexed under Lymphatic Abnormalities; 17 are open to participants now.
This study's planned enrollment of 70 is above the median of 46 across 28 interventional studies indexed under Lymphatic Abnormalities.
Browse Lymphatic Abnormalities studies →Fondazione Policlinico Universitario Agostino Gemelli IRCCS is the lead sponsor of 952 studies on the registry; 541 are open to participants now.
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Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Genetic profiling (targeted NGS panel) performed on affected tissue sample
Genetic: Genetic profiling of all eligible patients
Performed genetic profiling in DNA extracted from fresh tissue or FFPE in all patients affected by lymphatic malformation recruited
Estimate the prevalence and incidence of ML in Italy
Data collection derived from the computerized registry created for the study
Time frame: 20 years
Institution of a biobank collecting biological samples of lymphatic malformations
collection of biological samples (blood, buccal swab, tissue), associated with clinical data, usable by the national and international scientific community (researchers/companies) and aimed at improving knowledge in this field.
Time frame: 20 years
Characterize potential genotype-phenotype associations
The registry institution and the prospective collection of genetic data will allow the definition of potential genotype phenotype association
Time frame: 20years
Natural evolution of lymphatic malformations
Describe natural evolution of lymphatic malformations according to genetic defects
Time frame: 20years
Evaluate the short and long-term (< or > 2 years) outcome of LM patients
Comparison between of conservative (vascular laser, scleroembolization, compression therapy), surgical and pharmacological treatment performed by calculating the number of procedures needed during the observation period in the study as well as evaluate the outcome of specialist center intake by calculating the number of patients lost to follow-up, number of patients who changed centers, choice of single-specialty vs multispecialty follow-up
Time frame: 20years
Evaluate quality of life status in this specific patient cohort
Analyze responses to questionnaires on quality of life, pain, sleep quality, adaptive skills, and parenting stress
Time frame: 20years
Started Jun 2024 (actual). Primary completion is estimated for Jun 2043, 228 months after the start.
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