Weekly Sirolimus for Lymphatic and Venous Malformations

Overseen By Stephnie Munie, BS

Age: Any Age

Sex: Any

Trial Phase: Phase 2

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 All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 6 months

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if taking sirolimus (Rapamune) once a week can effectively treat venous and lymphatic malformations, conditions where blood or lymph vessels form incorrectly. Current treatments are limited, and while daily sirolimus has shown promise, it can cause serious side effects. The study will assess patient satisfaction with weekly dosing and document any side effects. Individuals aged 2 years or older with these malformations may be suitable for the trial. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that sirolimus is generally safe for treating venous malformations. One study found sirolimus effective and well-tolerated, particularly for patients unresponsive to other treatments. Another study supports these findings, demonstrating that sirolimus safely manages complex blood vessel issues. However, some side effects, such as low white blood cell counts, mouth sores, and changes in lab results, can occur and may sometimes be serious.

The current trial tests a weekly dose, which might reduce side effects. As this is a Phase 2 trial, the researchers are still studying its safety, but existing research provides a positive outlook on its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for lymphatic and venous malformations, which generally involve surgery or sclerotherapy, Sirolimus offers a novel approach by targeting the mTOR pathway. This pathway is crucial for cell growth and proliferation, and Sirolimus helps to regulate it, potentially reducing the growth of abnormal blood vessels. Researchers are excited about Sirolimus because it is administered orally, making it less invasive than traditional methods, and it has shown promise in stabilizing or reducing the size of these malformations. This could lead to fewer complications and an improved quality of life for patients.

What evidence suggests that weekly sirolimus might be an effective treatment for venous and lymphatic malformations?

Research has shown that sirolimus, the treatment under study in this trial, can help treat venous and lymphatic malformations. Studies have found it particularly useful for individuals when other treatments have failed. Sirolimus can reduce the size of affected areas and alleviate symptoms such as pain and bleeding. It also enhances the quality of life for those with capillary lymphatic venous malformations. Although sirolimus has shown promise, it can cause side effects. This trial aims to determine a weekly dose that is effective while minimizing risks. ^{1 5 6 7 8}

Who Is on the Research Team?

Chelsea Shope, MSCR

Principal Investigator

Medical University of South Carolina

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Sirolimus

Trial Overview The 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.

How Is the Trial Designed?

Group I: Treatment Group Experimental Treatment 1 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

Who Is Running the Clinical Trial?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

Published Research Related to This Trial

Sirolimus shows promise in treating pediatric lymphatic malformations, with 19 studies reviewed involving 97 patients, but the overall efficacy and safety profile is still uncertain due to a lack of high-quality research.

Mild-to-moderate adverse events were reported in 94 cases, highlighting the need for systematic reporting of side effects to help clinicians manage treatment risks, especially in younger children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sirolimus treatment for paediatric head and neck lymphatic malformations: a systematic review. Saibene, AM., Rosso, C., Felisati, G., et al.[2023]

A 30-year-old male with a rare intraorbital lymphatic-venous malformation was successfully treated with sirolimus, resulting in complete clinical and radiologic remission after 18 months.

The treatment was generally well-tolerated, with only mild cold-like symptoms and temporary liver enzyme elevation noted, and no major adverse effects were reported, indicating sirolimus may be a safe option for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraorbital lymphatic-venous malformation in an adult patient: is sirolimus the key? Ruiz Velasco Santacruz, A., Nieva Pascual, I., Cifuentes Canorea, P., et al.[2023]

A pilot study involving four patients with various vascular malformations found that topical sirolimus gel (0.2%) was safe, with no adverse events reported and no detectable blood levels of sirolimus.

The treatment showed clinical effectiveness comparable to systemic sirolimus, with 50% of patients experiencing mild improvement, particularly in blue rubber bleb nevus syndrome, indicating potential for topical sirolimus in treating venous and capillary malformations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Verification of the efficacy of topical sirolimus gel for systemic rare vascular malformations: a pilot study. Wataya-Kaneda, M., Maeda, S., Nakamura, A., et al.[2023]

Sirolimus, a new medical therapy, has shown promise in treating lymphatic malformations in a female infant, indicating its potential as an effective alternative to traditional treatments like sclerotherapy and surgery.

The case report highlights both improvements and complications during the first 9 months of treatment, suggesting that while sirolimus can be beneficial, careful monitoring is necessary to manage any adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sirolimus: A Successful Medical Treatment for Head and Neck Lymphatic Malformations. Curry, S., Logeman, A., Jones, D.[2020]

Sirolimus, an antiangiogenetic and antiproliferative agent, has been shown to be a safe and effective treatment for pediatric patients with vascular malformations (VMs) that cover wide anatomical areas, with five out of six patients achieving partial responses after an average treatment duration of 13 months.

The effectiveness of sirolimus appears to increase with the proportion of lymphatic components in the vascular malformation, and all patients tolerated the treatment well with acceptable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-center experience with sirolimus therapy for vascular malformations. Yesil, S., Tanyildiz, HG., Bozkurt, C., et al.[2022]

A 10-year-old boy with an orbital venolymphatic malformation was initially treated with local sclerotherapy, but the condition relapsed, highlighting the need for effective long-term management strategies.

The relapse was successfully managed with oral sirolimus, suggesting that this medication may be a promising treatment option for lymphatic malformations, although further studies are needed to establish optimal dosing and broader applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of orbital lymphatic malformation with oral sirolimus: a case report. Alba-Linero, C., García-Lorente, M., Rachwani-Anil, R., et al.[2023]

Sirolimus treatment showed promising results in patients with extensive lymphatic malformations, with 60 out of 71 patients experiencing partial remission, indicating its potential efficacy as a therapeutic option.

Common side effects of sirolimus included hyperlipidemia and neutropenia, highlighting the need for careful monitoring during treatment, as well as the necessity for further randomized controlled studies to better understand its long-term safety and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Lymphatic Malformations with the mTOR Inhibitor Sirolimus: A Systematic Review. Wiegand, S., Wichmann, G., Dietz, A.[2021]

Sirolimus is effective in reducing the volume of pediatric cervicofacial lymphatic malformations (LMs), with 78% of patients showing a reduction of 20% or more on MRI, and 32% achieving a reduction of 50% or more.

The treatment also leads to significant clinical improvements, with 97% of patients reporting some benefit, and particularly helps airway LMs, as 33% of tracheostomy-dependent patients were able to be decannulated after starting sirolimus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sirolimus for Pediatric Cervicofacial Lymphatic Malformation: A Systematic Review and Meta-Analysis. Kamhieh, Y., Mitra, R., Burnett, T., et al.[2023]

In a study of 56 children with complex lymphatic malformations treated with oral sirolimus, the total effective rate for reducing lesions was 89.3%, indicating high efficacy of the treatment.

Sirolimus was found to be safe, with no serious adverse reactions reported, suggesting it could be a preferable alternative to surgical interventions for managing these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of sirolimus in the treatment of complex lymphatic malformations: Single center report of 56 cases. Tian, R., Liang, Y., Zhang, W., et al.[2021]

In a study of 14 patients receiving off-label sirolimus therapy for various vascular anomalies, 17 severe adverse events (SAEs) were identified, with viral pneumonia being the most common, leading to one death in an infant.

Most SAEs occurred within the first year of treatment, highlighting the need for careful monitoring, especially in young patients and those with complex underlying conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe adverse events during sirolimus "off-label" therapy for vascular anomalies. Rössler, J., Baselga, E., Davila, V., et al.[2022]

Sirolimus has been found effective in reducing the size and symptoms of various vascular malformations, with significant improvements observed in 67% of patients with venous malformations and over 80% with lymphatic malformations after 6 months of treatment.

While side effects occurred in 53% of patients, they were generally mild, but there is a notable risk of recurrence of symptoms in 49% of patients who stopped treatment, highlighting the need for ongoing clinical trials to better understand the long-term safety and efficacy of sirolimus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A narrative review of the role of sirolimus in the treatment of congenital vascular malformations. Geeurickx, M., Labarque, V.[2022]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S2213333X25001192

Effectiveness and safety of sirolimus in the treatment ... Sirolimus is effective and safe for treating venous malformations, especially in patients unresponsive to conventional therapies.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9249683/

Efficacy of sirolimus in children with lymphatic ... Sirolimus could be an effective treatment for children with large complicated lymphatic malformations of the head and neck.

3. jamanetwork.com jamanetwork.com/journals/jamadermatology/fullarticle/2784291

Sirolimus (Rapamycin) for Slow-Flow Malformations in ... Overall, sirolimus was efficient for painful symptoms, especially among patients with combined malformations, and for bleeding, oozing, and quality of life ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2213333X25000654

A real-world study of sirolimus in the treatment of pediatric ... Sirolimus significantly decreased lesion volume and improved clinical symptoms in most patients with LMs, especially those with macrocystic components.

5. consultqd.clevelandclinic.org consultqd.clevelandclinic.org/mounting-evidence-supports-sirolimus-to-treat-capillary-lymphatic-venous-malformations

Sirolimus To Treat Capillary Lymphatic Venous Malformations Our key findings indicated that sirolimus effectively reduces complications and improves QOL in individuals with CLVM.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7535851/

Efficacy and safety of sirolimus in the treatment of vascular ... The purpose of this study was to evaluate the effectiveness and safety of sirolimus in the treatment of vascular malformations.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05050149

Study Evaluating the Safety and Efficacy of PTX-022 ... This study evaluates the safety and efficacy of PTX-022 (sirolimus) Topical Gel 3.9% w/w in the treatment of Microcystic Lymphatic Malformations. The ...

8. journals.lww.com journals.lww.com/jova/fulltext/2025/12000/safety_of_sirolimus_in_the_treatment_of_vascular.3.aspx

Safety of Sirolimus in the Treatment of Vascular Anomalies... There were 20 (95.2%) patients with vascular malformations and 1 (4.8%) patient with a vascular tumor (kaposiform hemangioendothelioma). Among those with ...