Weekly Sirolimus for Lymphatic and Venous Malformations
Recruiting in Palo Alto (17 mi)
Age: Any Age
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Medical University of South Carolina
Must be taking: Sirolimus
Must not be taking: CYP3A4 inhibitors, inducers
Disqualifiers: Transplant, Immunodeficiency, Infection, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Approved in 4 Jurisdictions
Trial Summary
What is the purpose of this trial?
This trial is testing if taking sirolimus once a week can help people with venous and lymphatic malformations. These patients have few treatment options. Sirolimus aims to reduce abnormal growths by affecting the immune system. The study will also check for side effects and patient satisfaction over several months. Sirolimus has been used in various studies to treat lymphatic malformations and has shown potential in stabilizing lung function in patients with lymphangioleiomyomatosis.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking certain medications that affect how sirolimus works. It's best to discuss your current medications with the trial team.
What data supports the effectiveness of the drug Sirolimus for treating lymphatic and venous malformations?
Research shows that Sirolimus has been effective in treating lymphatic malformations, especially in children, by reducing the size and symptoms of these growths. It has been used successfully in cases where other treatments like surgery or sclerotherapy (a procedure to shrink blood vessels) were not effective.12345
Is sirolimus safe for treating lymphatic and venous malformations?
Sirolimus has shown a generally favorable safety profile in treating vascular anomalies, though some severe adverse events have been reported during its off-label use. In a study using topical sirolimus gel, no adverse events were observed, suggesting it may be safe for certain types of vascular malformations.15678
How is the drug Sirolimus unique in treating lymphatic and venous malformations?
Sirolimus is unique because it is an oral medication that targets the mTOR pathway, which helps control cell growth and proliferation, making it effective for treating vascular malformations that are difficult to manage with traditional methods like surgery or sclerotherapy. It offers a non-invasive option for patients with extensive or recurrent malformations, where other treatments have limited success.2591011
Eligibility Criteria
This trial is for individuals aged 2 years and older with venous, lymphatic, or venolymphatic malformations. It excludes those with contraindications to sirolimus, on certain other medications, pregnant women or those who might become pregnant without effective contraception, and children with a history of transplant or immunodeficiency.Inclusion Criteria
You have malformations in your veins, lymphatic system, or both.
Patients aged 2 years and older
Exclusion Criteria
Children who have had previous immune system problems.
Children who have had a severe or life-threatening infection in the past.
If you are a child taking medications that inhibit CYP3A4.
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Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive once weekly dosed sirolimus for the treatment of venous and lymphatic malformations
6 months
Monthly visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
2 months
2 visits (in-person)
Open-label extension (optional)
Participants may opt into continuation of treatment long-term
Long-term
Treatment Details
Interventions
- Sirolimus (mTOR inhibitor)
Trial OverviewThe study tests if taking the oral medication Sirolimus once a week can treat venous and lymphatic malformations effectively. The treatment lasts for six months with an option to continue thereafter. Patient satisfaction and side effects will also be evaluated.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Treatment GroupExperimental Treatment1 Intervention
Sirolimus is already approved in United States, European Union, Canada, Japan for the following indications:
🇺🇸 Approved in United States as Rapamune for:
- Prevention of organ rejection in kidney transplant patients
- Treatment of lymphangioleiomyomatosis (LAM)
🇪🇺 Approved in European Union as Rapamune for:
- Prevention of organ rejection in kidney transplant patients
- Treatment of lymphangioleiomyomatosis (LAM)
🇨🇦 Approved in Canada as Rapamune for:
- Prevention of organ rejection in kidney transplant patients
- Treatment of lymphangioleiomyomatosis (LAM)
🇯🇵 Approved in Japan as Rapamune for:
- Prevention of organ rejection in kidney transplant patients
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Medical University of South CarolinaCharleston, SC
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Who Is Running the Clinical Trial?
Medical University of South CarolinaLead Sponsor
References
Sirolimus treatment for paediatric head and neck lymphatic malformations: a systematic review. [2023]This PRISMA-compliant systematic review aimed to assess risks and benefits of sirolimus treatment for paediatric lymphatic malformations by focusing not only on treatment efficacy but also on possible treatment-related adverse events, and treatment combinations with other techniques.
Treatment of orbital lymphatic malformation with oral sirolimus: a case report. [2023]It is estimated that lymphatic malformations in children account for 6% of all benign vascular malformations. New medical therapies have been developed for the management of lymphatic orbital disease. The purpose of this article was to describe a clinical case of orbital venolymphatic malformation in a 10-year-old boy, causing proptosis and palpebral edema. The lesion was initially treated with local sclerotherapy. However, the lesion relapsed, and was successfully treated with oral sirolimus. Prospective studies are warranted to determine the appropriate dose and extend the indications of sirolimus in these patients.
Sirolimus for Pediatric Cervicofacial Lymphatic Malformation: A Systematic Review and Meta-Analysis. [2023]This study is a systematic review and meta-analysis of the efficacy and safety of sirolimus in the management of pediatric cervicofacial lymphatic malformations (LMs).
Effectiveness of sirolimus in the treatment of complex lymphatic malformations: Single center report of 56 cases. [2021]Lymphatic malformations are common congenital vascular lesions. Neither surgical resection nor other surgical treatments have been found to be effective for invasive cases. Recent research has suggested that sirolimus is effective in treating complex lymphatic malformations (LMs). We aimed to evaluate the effectiveness and safety of oral sirolimus for children living with LMs in our hospital.
Sirolimus: A Successful Medical Treatment for Head and Neck Lymphatic Malformations. [2020]Lymphatic malformations are abnormalities that arise in the developing lymphatic system, most frequently presenting in the head and neck. They are typically treated with sclerotherapy, laser therapy, or surgery for localized lesions. Sirolimus, an inhibitor of the mammalian target of rapamycin, is a relatively new medical therapy for the treatment of vascular malformations. This case report presents the improvements and complications seen in a female infant who was diagnosed with a large lymphatic malformation on prenatal ultrasound and has been treated with sirolimus during the first 9 months of life.
A narrative review of the role of sirolimus in the treatment of congenital vascular malformations. [2022]Vascular malformations arise from defects in the morphologic development of the vascular system and can have an impact on quality of life and/or lead to severe complications. To date, vascular malformations are frequently managed by invasive techniques, after which recurrence is common. Sirolimus, a downstream inhibitor of the phosphatidylinositol 3 kinase/AKT pathway and best known for its immunosuppressive effect, has been used off-label for lesions for which approved therapies were associated with unsatisfactory results or recurrence. The aim of this study was to review the available data on the effect of sirolimus on the size and symptoms of different types of malformations and to summarize the main safety issues.
Severe adverse events during sirolimus "off-label" therapy for vascular anomalies. [2022]Clinical studies have shown low toxicity and a favorable safety profile for sirolimus in vascular anomalies. Here, we describe severe adverse events (SAEs) observed during "off-label use" for vascular anomalies.
Verification of the efficacy of topical sirolimus gel for systemic rare vascular malformations: a pilot study. [2023]Numerous clinical trials of sirolimus, an inhibitor of mechanistic/mammalian target of rapamycin complex 1, for the treatment of vascular malformations have been conducted. However, aside from lymphatic malformations, the efficacy of sirolimus for venous and capillary malformations has not been established. Moreover, no generalized venous or capillary malformations have been treated with topical sirolimus. To evaluate the safety and efficacy of topical sirolimus for venous and capillary malformations and to compare the efficacy of topical and systemic sirolimus therapy, an open-label single-arm pilot study with 0.2% sirolimus gel was conducted from July 19, 2019, to January 30, 2020, in four patients diagnosed with different vascular malformations (blue rubber bleb nevus syndrome, common venous malformation, phakomatosis pigmentovascularis type IVb, and angiokeratoma in Fabry disease). The primary endpoint was the safety evaluation of sirolimus gel. The main secondary endpoint was the improvement rate evaluated by the Central Judgment Committee at 12 weeks using photographs. No adverse events were observed. Blood sirolimus was not detected in any patient. Two patients (50%) had mild improvement, and the remaining two patients (50%) showed no change after 12 weeks of treatment. Blue rubber bleb nevus syndrome, a generalized venous malformation, showed the greatest response. In conclusion, 0.2% sirolimus gel was found to be as clinically effective as systemic sirolimus treatment in patients with venous and capillary malformations and more effective for early active lesions, even systemic venous malformations.
Intraorbital lymphatic-venous malformation in an adult patient: is sirolimus the key? [2023]Intraorbital lymphatic-venous malformations are rare lesions that represent a therapeutic challenge given their location and high rate of recurrence, with only a few cases in adult patients having been published in the literature. We present the case of a 30-year-old male with a right intraorbital lymphatic-venous malformation treated with sirolimus at a dose of 4 mg/day with complete clinical and radiologic remission. Mild cold-like symptoms ensued during the first week of treatment and elevation of liver function enzymes and D-dimer occurred in the context of acute SARS-CoV-2 pneumonia. No major adverse effects were documented. After 18 months of treatment, the patient remains asymptomatic and ophthalmologic examinations including optical coherence tomography and visual field test are within normal values.
Single-center experience with sirolimus therapy for vascular malformations. [2022]Vascular malformations (VMs) are described as congenital malformations of the vasculature derived from capillaries, veins, lymphatic vessels, arteries, or a combination of these vessels. They can cause significant morbidity resulting from soft tissue hypertrophy-related disfiguration, bony abnormalities, and even organ compromise. They are usually treated with various interventional procedures to achieve local control; however, the chance of success decreases as the anatomical distribution of the malformation widens. Unfortunately, medical treatment options have been quite limited in these patients. Sirolimus is an antiangiogenetic and antiproliferative pharmacologic agent that has been used for the management of VM in the last decade. We report 6 pediatric patients (4 with capillary lymphaticovenous malformations, 1 with lymphaticovenous malformation, and 1 with venous malformation) seen at our clinic within the last 2 years with lesions covering wide anatomical areas. After the patients had unsuccessfully undergone various treatments at various centers, they were treated at our facility with peroral sirolimus. The mean duration of treatment was 13 months, but in 3 patients, tapered dosing continues. Five patients achieved partial responses. The response to sirolimus treatment increased as the lymphatic component of the VM increased. All patients tolerated sirolimus well; side effects were acceptable. Sirolimus is a safe and effective medical treatment for widely distributed VMs with significant lymphatic components and no further local treatment option.
Treatment of Lymphatic Malformations with the mTOR Inhibitor Sirolimus: A Systematic Review. [2021]Extensive lymphatic malformations are low-flow vascular malformations that can cause devastating complications. Treatment of these malformations is challenging. This systematic review presents current use of sirolimus in patients with extensive lymphatic malformations.