Clinical trial NCT06160739: Role of Sirolimus in Treatment of Microcystic , Mixed Lymphatic and Vascular Malformations
Official title: Role of Sirolimus in Treatment of Microcystic , Mixed Lymphatic and Vascular Malformations
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Microcystic Lymphatic Malformation
Combined Vascular Malformation
Vascular Malformations
Lead sponsor: Sohag University
Sponsor class: OTHER
First posted: 2023-12-07
Enrollment: 10
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: * from age 6 months to 12 years , not before 6 months to complete their vaccination program \& maturation of hepatic enzymes .
* Patients diagnosed with microcystic \& mixed Lymphatic malformations .
* After failure of other lines of treatment as regard propranolol , steroid for infantile haemangiomas \& Vascular malformations and lymphovascular malformations .
* After failure of surgical excision \& injection of bleomycin of Lympho-vascular malformations

Brief summary: Lympho-vascular malformations result from errors in embryologic vasculogenesis involving capillaries, veins, arteries, lymphatics, or a combination of these. Infantile haemangiomas \& Vascular malformations like : Capillary malformations \& Venous malformations : they increase in size and never regress on their own. \& They are generally present at birth, they enlarge in response to infection, hormonal changes or trauma . Lymphatic malformations can be classified into macrocystic (cyst diameter \>1cm), microcystic (cyst diameter \<1 cm), or mixed , in macrocystic lymphatic malformations, surgery and sclerotherapy are effective . Surgery of microcystic lymphatic malformations remains challenging due to their infiltrative nature \& Sclerotherapy is often impossible. As especially large microcystic and mixed malformations are still a therapeutic challenge, pharmaceutical treatment as sirolimus is used in last years as main line of treatment with great efficacy.

Detailed description: Lympho-vascular malformations result from errors in embryologic vasculogenesis involving capillaries, veins, arteries, lymphatics, or a combination of these. Infantile haemangiomas \& Vascular malformations like : Capillary malformations \& Venous malformations : they increase in size and never regress on their own. \& They are generally present at birth, they enlarge in response to infection, hormonal changes or trauma . Lymphatic malformations can be classified into macrocystic (cyst diameter \>1cm), microcystic (cyst diameter \<1 cm), or mixed , in macrocystic lymphatic malformations, surgery and sclerotherapy are effective . Surgery of microcystic lymphatic malformations remains challenging due to their infiltrative nature \& Sclerotherapy is often impossible. As especially large microcystic and mixed malformations are still a therapeutic challenge, pharmaceutical treatment as sirolimus is used in last years as main line of treatment with great efficacy. Sirolimus is a natural macrolide isolated from a bacteria strain of the Streptomyces genus \& Streptomyces hygroscopicus . It was initially used as an antibiotic and antifungal agent, subsequent studies have revealed impressive cytostatic, antiproliferative, and immunosuppressive properties . Sirolimus not only prevents the growth of abnormal lymphatics but also induces the partial regression of lesions, without apparent effects on normal lymphatics .

Eligibility criteria: Inclusion Criteria:

* from age 6 months to 12 years , not before 6 months to complete their vaccination program \& maturation of hepatic enzymes .
* Patients diagnosed with microcystic \& mixed Lymphatic malformations .
* After failure of other lines of treatment as regard propranolol , steroid for infantile haemangiomas \& Vascular malformations and lymphovascular malformations .
* After failure of surgical excision \& injection of bleomycin of Lympho-vascular malformations

Exclusion Criteria:

* Macrocystic Lymphatic malformations \& high flow vascular malformations like arterio-venous malformations .
* An active infection that requires systemic treatment during the attack .
* Side effects of the drug as ( history of an allergic reaction to sirolimus or patients who develop severe allergic reaction to drug during treatment , hyperlipidemia , leucopenia , etc... )
* Chronic liver or kidney disease or on chronic drug treatment as (steroids, interferon or chemotherapeutic agents) .
* An immunodeficiency condition such as a human immunodeficiency viral infection or primary immunodeficiency disease.
* Patients who received drug less than 6 months duration .

Primary outcomes:
measure: changes in size of the lesion
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Sohag
country: Egypt
facility: Sohag university Hospital
Study officials:
References:
citation: Sadick M, Muller-Wille R, Wildgruber M, Wohlgemuth WA. Vascular Anomalies (Part I): Classification and Diagnostics of Vascular Anomalies. Rofo. 2018 Sep;190(9):825-835. doi: 10.1055/a-0620-8925. Epub 2018 Jun 6.
citation: Vlahovic AM, Vlahovic NS, Haxhija EQ. Sirolimus for the Treatment of a Massive Capillary-Lymphatico-Venous Malformation: A Case Report. Pediatrics. 2015 Aug;136(2):e513-6. doi: 10.1542/peds.2014-3469. Epub 2015 Jul 6.
citation: Muller-Wille R, Wildgruber M, Sadick M, Wohlgemuth WA. Vascular Anomalies (Part II): Interventional Therapy of Peripheral Vascular Malformations. Rofo. 2018 Feb 7. doi: 10.1055/s-0044-101266. Online ahead of print.
citation: Adams DM, Wentzel MS. The role of the hematologist/oncologist in the care of patients with vascular anomalies. Pediatr Clin North Am. 2008 Apr;55(2):339-55, viii. doi: 10.1016/j.pcl.2008.01.007.