Lymphatic MalformationIReg-LMNCT06892964
Institution of an Italian Registry and Biobank for Biological Sample Collection
A study testing Genetic profiling of all eligible patients in people with Lymphatic Malformation and Lymphatic Abnormality, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.
Trial summary
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. Read more about this study
- Who is it for?
- Ages Up to 100 years
- Conditions the study is for
- Lymphatic Malformation, Lymphatic Abnormality, Lymphangioma
- What is being tested?
- Genetic profiling of all eligible patients
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 1 siteItaly
- Study dates
- 27 Jun 2024to 27 Jun 2044
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 100 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age 0-100 years
- Signed informed consent.
- Individuals with any type of ML (isolated, syndromic, congenital or acquired, with or without molecular confirmation) identified by participating centers
Who cannot join
- Patients whose clinical picture is not compatible with points a) (b) and (c) of the inclusion criteria, as assessed by the Investigator.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
Department of Woman and Child Health and Public Health, Fondazione Policlinico A. Gemelli, IRCCS
Roma, 00168
Chiara Leoni, MD, PhD, 0039063381344, chiara.leoni@policlinicogemelli.it
About this study
Official title: Prospective and Retrospective Clinical Study of Lymphatic Malformations: Institution of an Italian REGistry of Lymphatic Malformations and of a Biobank for Biological Sample Collection
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.
Read more
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;
Read the detailed description
ENDPOINT Primary endpoint
- To estimate the prevalence and incidence of ML in Italy using data derived from the computerized registry created Secondary endpoints
- To create a collection of biological samples, associated with clinical data, usable by the national and international scientific community (researchers/companies) and aimed at improving knowledge in this field.
- Characterize potential genotype-phenotype associations
- Describe how the phenotype also evolves over time in relation to the genotype found
- Evaluate the short-term (within the first two years after the procedure was performed) and long-term (>2 years) outcome 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;
- Analyze responses to questionnaires on quality of life, pain, sleep quality, adaptive skills, and parenting stress;
- Define a nationally shared diagnostic for ML.
References:
- https://snlg.iss.it/wp-content/uploads/2021/04/LG-276-Anomalie-Vascolari.pdf
- International Society for the Study of Vascular Anomalies. ISSVA Classification of Vascular Anomalies ©. Published 2018. Accessed May 13, 2022. issva.org/classification
- Leboulanger N, Bisdorff A, Boccara O, Dompmartin A, Guibaud L, Labreze C, Lagier J, Lebrun- Vignes B, Herbreteau D, Joly A, Malloizel-Delaunay J, Martel A, Munck S, Saint-Aubin F, Maruani A. French national diagnosis and care protocol (PNDS, protocole national de diagnostic et de soins): cystic lymphatic malformations. Orphanet J Rare Dis. 2023 Jan 13;18(1):10. doi: 10.1186/s13023- 022-02608-y
- Ghaffarpour N, Baselga E, Boon LM, Diociaiuti A, Dompmartin A, Dvorakova V, El Hachem M, Gasparella P, Haxhija E, Kyrklund K, Irvine AD, Kapp FG, Rößler J, Salminen P, van den Bosch C, van der Vleuten C, Kool LS, Vikkula M. The VASCERN-VASCA working group diagnostic and management pathways for lymphatic malformations. Eur J Med Genet. 2022 Dec;65(12):104637. doi: 10.1016/j.ejmg.2022.104637. Epub 2022 Oct 9. PMID: 36223836.
- Moneghini L, Sangiorgio V, Tosi D, Colletti G, Melchiorre F, Baraldini V, Graziani D, Alfano RM, Vercellio G, Bulfamante G. Head and neck vascular anomalies. A multidisciplinary approach and diagnostic criteria. Pathologica. 2017 Mar;109(1):47-59. PMID: 28635993.
- Lee SY, Loll EG, Hassan AES, Cheng M, Wang A, Farmer DL. Genetic and Molecular Determinants of Lymphatic Malformations: Potential Targets for Therapy. J Dev Biol. 2022;10(1). doi:10.3390/jdb10010011
- Snyder E, Sarma A, Borst AJ, Tekes A. Lymphatic Anomalies in Children: Update on Imaging Diagnosis, Genetics and Treatment. Am J Roentgenol. Published online 2022. doi:10.2214/ajr.21.27200
- Nathan N, Keppler-Noreuil KM, Biesecker LG, Moss J, Darling TN. Mosaic Disorders of the PI3K/PTEN/AKT/TSC/mTORC1 Signaling Pathway. Dermatol Clin. 2017;35(1):51-60. doi:10.1016/j.det.2016.07.001
- Gomes IP, Guimarães LM, Pereira T dos SF, et al. Assessment of PI3K/AKT and MAPK/ERK pathways activation in oral lymphatic malformations. Oral Surg Oral Med Oral Pathol Oral Radiol. 2022;133(2):216-220. doi:10.1016/j.oooo.2021.08.018
- Wu C, Song D, Guo L, Wang L. Refractory Head and Neck Lymphatic Malformation in Infants Treated With Sirolimus: A Case Series. Front Oncol. 2021;11:616702. doi:10.3389/fonc.2021.616702
- Holm A, Te Loo M, Schultze Kool L, et al. Efficacy of Sirolimus in Patients Requiring Tracheostomy for Life-Threatening Lymphatic Malformation of the Head and Neck: A Report From the European Reference Network. Front Pediatr. 2021;9:697960. doi:10.3389/fped.2021.697960
- Amodeo I, Colnaghi M, Raffaeli G, et al. The use of sirolimus in the treatment of giant cystic lymphangioma: Four case reports and update of medical therapy. Medicine (Baltimore). 2017;96(51):e8871. doi:10.1097/MD.0000000000008871
- Holm A, Te Loo M, Schultze Kool L, et al. Efficacy of Sirolimus in Patients Requiring Tracheostomy for Life-Threatening Lymphatic Malformation of the Head and Neck: A Report From the European Reference Network. Front Pediatr. 2021;9:697960. doi:10.3389/fped.2021.697960
- Amodeo I, Colnaghi M, Raffaeli G, et al. The use of sirolimus in the treatment of giant cystic lymphangioma: Four case reports and update of medical therapy. Medicine (Baltimore). 2017;96(51):e8871. doi:10.1097/MD.0000000000008871
- 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
- Triana P, Miguel M, Díaz M, Cabrera M, López Gutiérrez JC. Oral Sirolimus: An Option in the Management of Neonates with Life-Threatening Upper Airway Lymphatic Malformations. Lymphat Res Biol. 2019;17(5):504-511. doi:10.1089/lrb.2018.0068
- Curry S, Logeman A, Jones D. Sirolimus: A Successful Medical Treatment for Head and Neck Lymphatic Malformations. Case Rep Otolaryngol. 2019;2019:2076798. doi:10.1155/2019/2076798
- Wenger TL, Ganti S, Bull C, Lutsky E, Bennett JT, Zenner K, Jensen DM, Dmyterko V, Mercan E, Shivaram GM, Friedman SD, Bindschadler M, Drusin M, Perkins JN, Kong A, Bly RA, Dahl JP, Bonilla- Velez J, Perkins JA. Alpelisib for the treatment of PIK3CA-related head and neck lymphatic malformations and overgrowth. Genet Med. 2022 Nov;24(11):2318-2328. doi: 10.1016/j.gim.2022.07.026
- Shaheen MF, Tse JY, Sokol ES, Masterson M, Bansal P, Rabinowitz I, Tarleton CA, Dobroff AS, Smith TL, Bocklage TJ, Mannakee BK, Gutenkunst RN, Bischoff J, Ness SA, Riedlinger GM, Groisberg R, Pasqualini R, Ganesan S, Arap W. Genomic landscape of lymphatic malformations: a case series and response to the PI3Kα inhibitor alpelisib in an N-of-1 clinical trial. Elife. 2022 Jul 5;11:e74510. doi: 10.7554/eLife.74510. PMID: 35787784; PMCID: PMC9255965.
- Delestre F, Venot Q, Bayard C, Fraissenon A, Ladraa S, Hoguin C, Chapelle C, Yamaguchi J, Cassaca R, Zerbib L, Magassa S, Morin G, Asnafi V, Villarese P, Kaltenbach S, Fraitag S, Duong JP, Broissand C, Boccara O, Soupre V, Bonnotte B, Chopinet C, Mirault T, Legendre C, Guibaud L, Canaud G. Alpelisib administration reduced lymphatic malformations in a mouse model and in patients. Sci Transl Med. 2021 Oct 6;13(614):eabg0809. doi: 10.1126/scitranslmed.abg0809
- Being tested
- Genetic profiling of all eligible patients
- Medical subject headings
- Lymphatic Abnormalities, Lymphangioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Genetic profiling of all eligible patientsGenetic
Performed genetic profiling in DNA extracted from fresh tissue or FFPE in all patients affected by lymphatic malformation recruited
| Study group | Role | What they receive |
|---|---|---|
| Pstients with isolated lymphatic malformation | Experimental | Genetic profiling (targeted NGS panel) performed on affected tissue sample Receives: Genetic: Genetic profiling of all eligible patients |
What is being measured
The primary outcome is the main question the study is designed to answer.
Estimate the prevalence and incidence of ML in Italy
Data collection derived from the computerized registry created for the study
Measured: 20 years
Secondary outcomes (5)
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.
Measured: 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
Measured: 20years
Natural evolution of lymphatic malformations
Describe natural evolution of lymphatic malformations according to genetic defects
Measured: 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
Measured: 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
Measured: 20years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2025
- Study start27 Jun 2024
- Primary completion27 Jun 2043 (estimated)
- Study completion27 Jun 2044 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Lymphatic MalformationStudies of the same condition, open and under way.
- More trials run by Fondazione Policlinico Universitario Agostino Gemelli IRCCSThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Chiara Leoni, Principal investigator, Fondazione Policlinico Universitario Agostino Gemelli IRCCS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06892964
- Sponsor's protocol ID
- 6221
- Acronym
- IReg-LM
- Status last verified
- Jul 2024
- First submitted
- 18 Mar 2025
- Last updated
- 25 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Trevisan V, De Corso E, Viscogliosi G, Onesimo R, Cina A, Panfili M, Perri L, Agazzi C, Giorgio V, Rigante D, Vento G, Papacci P, Paradiso FV, Silvaroli S, Nanni L, Resta N, Castori M, Galli J, Paludetti G, Zampino G, Leoni C. A multi-step approach to overcome challenges in the management of head and neck lymphatic malformations, and response to treatment. Orphanet J Rare Dis. 2024 Jul 23;19(1):276. doi: 10.1186/s13023-024-03200-2.
PubMed 39044220
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective and Retrospective Clinical Study of Lymphatic Malformations: Institution of an Italian REGistry of Lymphatic Malformations and of a Biobank for Biological Sample Collection
- ClinicalTrials.gov ID
- NCT06892964
- Acronym / sponsor ID
- IReg-LM / 6221
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- Fondazione Policlinico Universitario Agostino Gemelli IRCCSUniversity, hospital or other
- Study start
- 27 Jun 2024 (actual)
- Primary completion
- 27 Jun 2043 (estimated)
- Study completion
- 27 Jun 2044 (estimated)
- First posted
- 25 Mar 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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;
Detailed description
ENDPOINT Primary endpoint
- To estimate the prevalence and incidence of ML in Italy using data derived from the computerized registry created Secondary endpoints
- To create a collection of biological samples, associated with clinical data, usable by the national and international scientific community (researchers/companies) and aimed at improving knowledge in this field.
- Characterize potential genotype-phenotype associations
- Describe how the phenotype also evolves over time in relation to the genotype found
- Evaluate the short-term (within the first two years after the procedure was performed) and long-term (>2 years) outcome 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;
- Analyze responses to questionnaires on quality of life, pain, sleep quality, adaptive skills, and parenting stress;
- Define a nationally shared diagnostic for ML.
References:
- https://snlg.iss.it/wp-content/uploads/2021/04/LG-276-Anomalie-Vascolari.pdf
- International Society for the Study of Vascular Anomalies. ISSVA Classification of Vascular Anomalies ©. Published 2018. Accessed May 13, 2022. issva.org/classification
- Leboulanger N, Bisdorff A, Boccara O, Dompmartin A, Guibaud L, Labreze C, Lagier J, Lebrun- Vignes B, Herbreteau D, Joly A, Malloizel-Delaunay J, Martel A, Munck S, Saint-Aubin F, Maruani A. French national diagnosis and care protocol (PNDS, protocole national de diagnostic et de soins): cystic lymphatic malformations. Orphanet J Rare Dis. 2023 Jan 13;18(1):10. doi: 10.1186/s13023- 022-02608-y
- Ghaffarpour N, Baselga E, Boon LM, Diociaiuti A, Dompmartin A, Dvorakova V, El Hachem M, Gasparella P, Haxhija E, Kyrklund K, Irvine AD, Kapp FG, Rößler J, Salminen P, van den Bosch C, van der Vleuten C, Kool LS, Vikkula M. The VASCERN-VASCA working group diagnostic and management pathways for lymphatic malformations. Eur J Med Genet. 2022 Dec;65(12):104637. doi: 10.1016/j.ejmg.2022.104637. Epub 2022 Oct 9. PMID: 36223836.
- Moneghini L, Sangiorgio V, Tosi D, Colletti G, Melchiorre F, Baraldini V, Graziani D, Alfano RM, Vercellio G, Bulfamante G. Head and neck vascular anomalies. A multidisciplinary approach and diagnostic criteria. Pathologica. 2017 Mar;109(1):47-59. PMID: 28635993.
- Lee SY, Loll EG, Hassan AES, Cheng M, Wang A, Farmer DL. Genetic and Molecular Determinants of Lymphatic Malformations: Potential Targets for Therapy. J Dev Biol. 2022;10(1). doi:10.3390/jdb10010011
- Snyder E, Sarma A, Borst AJ, Tekes A. Lymphatic Anomalies in Children: Update on Imaging Diagnosis, Genetics and Treatment. Am J Roentgenol. Published online 2022. doi:10.2214/ajr.21.27200
- Nathan N, Keppler-Noreuil KM, Biesecker LG, Moss J, Darling TN. Mosaic Disorders of the PI3K/PTEN/AKT/TSC/mTORC1 Signaling Pathway. Dermatol Clin. 2017;35(1):51-60. doi:10.1016/j.det.2016.07.001
- Gomes IP, Guimarães LM, Pereira T dos SF, et al. Assessment of PI3K/AKT and MAPK/ERK pathways activation in oral lymphatic malformations. Oral Surg Oral Med Oral Pathol Oral Radiol. 2022;133(2):216-220. doi:10.1016/j.oooo.2021.08.018
- Wu C, Song D, Guo L, Wang L. Refractory Head and Neck Lymphatic Malformation in Infants Treated With Sirolimus: A Case Series. Front Oncol. 2021;11:616702. doi:10.3389/fonc.2021.616702
- Holm A, Te Loo M, Schultze Kool L, et al. Efficacy of Sirolimus in Patients Requiring Tracheostomy for Life-Threatening Lymphatic Malformation of the Head and Neck: A Report From the European Reference Network. Front Pediatr. 2021;9:697960. doi:10.3389/fped.2021.697960
- Amodeo I, Colnaghi M, Raffaeli G, et al. The use of sirolimus in the treatment of giant cystic lymphangioma: Four case reports and update of medical therapy. Medicine (Baltimore). 2017;96(51):e8871. doi:10.1097/MD.0000000000008871
- Holm A, Te Loo M, Schultze Kool L, et al. Efficacy of Sirolimus in Patients Requiring Tracheostomy for Life-Threatening Lymphatic Malformation of the Head and Neck: A Report From the European Reference Network. Front Pediatr. 2021;9:697960. doi:10.3389/fped.2021.697960
- Amodeo I, Colnaghi M, Raffaeli G, et al. The use of sirolimus in the treatment of giant cystic lymphangioma: Four case reports and update of medical therapy. Medicine (Baltimore). 2017;96(51):e8871. doi:10.1097/MD.0000000000008871
- 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
- Triana P, Miguel M, Díaz M, Cabrera M, López Gutiérrez JC. Oral Sirolimus: An Option in the Management of Neonates with Life-Threatening Upper Airway Lymphatic Malformations. Lymphat Res Biol. 2019;17(5):504-511. doi:10.1089/lrb.2018.0068
- Curry S, Logeman A, Jones D. Sirolimus: A Successful Medical Treatment for Head and Neck Lymphatic Malformations. Case Rep Otolaryngol. 2019;2019:2076798. doi:10.1155/2019/2076798
- Wenger TL, Ganti S, Bull C, Lutsky E, Bennett JT, Zenner K, Jensen DM, Dmyterko V, Mercan E, Shivaram GM, Friedman SD, Bindschadler M, Drusin M, Perkins JN, Kong A, Bly RA, Dahl JP, Bonilla- Velez J, Perkins JA. Alpelisib for the treatment of PIK3CA-related head and neck lymphatic malformations and overgrowth. Genet Med. 2022 Nov;24(11):2318-2328. doi: 10.1016/j.gim.2022.07.026
- Shaheen MF, Tse JY, Sokol ES, Masterson M, Bansal P, Rabinowitz I, Tarleton CA, Dobroff AS, Smith TL, Bocklage TJ, Mannakee BK, Gutenkunst RN, Bischoff J, Ness SA, Riedlinger GM, Groisberg R, Pasqualini R, Ganesan S, Arap W. Genomic landscape of lymphatic malformations: a case series and response to the PI3Kα inhibitor alpelisib in an N-of-1 clinical trial. Elife. 2022 Jul 5;11:e74510. doi: 10.7554/eLife.74510. PMID: 35787784; PMCID: PMC9255965.
- Delestre F, Venot Q, Bayard C, Fraissenon A, Ladraa S, Hoguin C, Chapelle C, Yamaguchi J, Cassaca R, Zerbib L, Magassa S, Morin G, Asnafi V, Villarese P, Kaltenbach S, Fraitag S, Duong JP, Broissand C, Boccara O, Soupre V, Bonnotte B, Chopinet C, Mirault T, Legendre C, Guibaud L, Canaud G. Alpelisib administration reduced lymphatic malformations in a mouse model and in patients. Sci Transl Med. 2021 Oct 6;13(614):eabg0809. doi: 10.1126/scitranslmed.abg0809
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pstients with isolated lymphatic malformation | Experimental | Genetic: Genetic profiling of all eligible patientsGenetic profiling (targeted NGS panel) performed on affected tissue sample |
Who may qualify
- Ages
- Up to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Age 0-100 years
- Signed informed consent.
- Individuals with any type of ML (isolated, syndromic, congenital or acquired, with or without molecular confirmation) identified by participating centers
Key exclusion criteria (1 listed)
- Patients whose clinical picture is not compatible with points a) (b) and (c) of the inclusion criteria, as assessed by the Investigator.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Genetic profiling of all eligible patientsPerformed genetic profiling in DNA extracted from fresh tissue or FFPE in all patients affected by lymphatic malformation recruited | Genetic | Pstients with isolated lymphatic malformation |
Primary outcome
Estimate the prevalence and incidence of ML in Italy
Time frame: 20 years
Data collection derived from the computerized registry created for the study
5 secondary outcomes
Institution of a biobank collecting biological samples of lymphatic malformations
Time frame: 20 years
Characterize potential genotype-phenotype associations
Time frame: 20years
Natural evolution of lymphatic malformations
Time frame: 20years
Evaluate the short and long-term (< or > 2 years) outcome of LM patients
Time frame: 20years
Evaluate quality of life status in this specific patient cohort
Time frame: 20years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2025.
- Results publication: PubMed 39044220Trevisan V, De Corso E, Viscogliosi G, Onesimo R, Cina A, Panfili M, Perri L, Agazzi C, Giorgio V, Rigante D, Vento G, Papacci P, Paradiso FV, Silvaroli S, Nanni L, Resta N, Castori M, Galli J, Paludetti G, Zampino G, Leoni C. A multi-step approach to overcome challenges in the management of head and neck lymphatic malformations, and response to treatment. Orphanet J Rare Dis. 2024 Jul 23;19(1):276. doi: 10.1186/s13023-024-03200-2.
Related trials for Lymphatic Malformation
RecruitingObservational study
Blood, Urine, and Tissue Collection for Cutaneous Lymphoma, Eczema, and Atopic Dermatitis Research
Cutaneous T-cell Lymphoma, Sezary Syndrome
Not yet recruitingPhase 1
Topical TOR-582 Treatment of Epistaxis in HHT
Hereditary Hemorrhagic Telangiectasia (HHT), Epistaxis
RecruitingObservational study
Defining the Natural History of Squamous Cell Carcinoma in Fanconi Anemia
Fanconi Anemia, Inherited Bone Marrow Failure Syndrome
RecruitingPhase 1/2
Harmony-HHT: ATV-1601 in Participants With Hereditary Hemorrhagic Telangiectasia (HHT)
Hereditary Hemorrhagic Telangiectasia (HHT), Osler Weber Rendu Disease
Not yet recruitingObservational study
Clinical Genetics Branch Eligibility Screening Survey
Melanoma, Li-Fraumeni Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Chiara Leoni principal investigator
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Genetic profiling of all eligible patients in people with Lymphatic Malformation and Lymphatic Abnormality, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 25 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Chiara Leoni, MD, PhD (00063381344, chiara.leoni@policlinicogemelli.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Estimate the prevalence and incidence of ML in Italy (time frame: 20 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06892964, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Mar 2025.