In short
Currently, there are 3 ongoing clinical trials exploring new treatments for lymphatic malformation. These studies are testing medications such as RLY-2608 and sirolimus (in both oral and topical forms) in patients of various ages. The trials are taking place in Belgium, France, Italy, and Spain.
Clinical trial locations
- Belgium
- France
- Italy
- Spain
Study on Sirolimus for Treating Cervico-facial Lymphatic Malformations in Patients with Poor Prognosis
This French trial is examining the effectiveness of Rapamycin (sirolimus) for treating lymphatic malformations in the head and neck area. These abnormal growths of the lymphatic system can cause significant health problems and are often difficult to treat successfully.
Who can participate: Patients aged 1 to 18 years with cervico-facial lymphatic malformations affecting one or both sides of the neck and face, or extending into the chest, are eligible. They must have ongoing symptoms causing pain or problems with breathing, swallowing, or speaking, with a symptom severity score below 8. Curative treatment should not be possible or should pose major risks. Participants must meet specific blood test requirements for neutrophil count, platelet count, hemoglobin, liver function, kidney function, and other markers. Both parents or guardians must provide informed consent, and patients must be covered by social security.
Who cannot participate: Pregnant or breastfeeding individuals are excluded, as are those with known allergies to Rapamycin, severe liver or kidney problems, serious illness in the past 6 months, or active infections requiring treatment. Patients currently in another clinical trial, with certain types of cancer history, or with drug or alcohol abuse in the past year cannot participate. Those with mental health conditions that might interfere with the study or who cannot follow study procedures are also excluded.
What the trial involves: Participants will receive Rapamycin as an oral solution, with dosage determined by the medical team. The study will monitor changes in malformation size over time using MRI scans at 3, 6, and 12 months. A reduction of at least one-fifth of the initial volume is considered a positive response. The trial will also examine how Rapamycin affects proteins and factors related to malformation growth. Rapamycin works by inhibiting a protein called mTOR, which plays a role in cell growth and proliferation.
Study on the Effects of Topical Sirolimus for Lingual Microcystic Lymphatic Malformations in Children and Adults
This French study is testing a topical (applied directly to the skin) form of sirolimus for treating lingual microcystic lymphatic malformations, which are clusters of cysts filled with lymph fluid or blood on the tongue. Even small lesions can cause significant problems including oozing, bleeding, infections, and difficulties with speech, chewing, or breathing.
Who can participate: The trial is open to individuals aged 5 years and older with lingual microcystic lymphatic malformations confirmed by clinical examination and MRI imaging. Participants must be covered by social security and provide written informed consent. For those under 18, their legal representative must also give consent. Participants must be able to comply with study requirements and follow the French mandatory immunization program.
Who cannot participate: Patients with other serious health conditions that could interfere with the study are excluded, as are those currently taking medications that might interact with the study treatment. Pregnant or breastfeeding individuals cannot participate. Those with allergies to the study medication or its ingredients, recent participation in another clinical trial, or a history of not following medical advice are also excluded. Anyone with conditions that study doctors believe would make participation unsafe is ineligible.
What the trial involves: Participants will apply a 1 mg/mL sirolimus solution once daily to the affected area of the tongue for 24 weeks. Assessments will occur at weeks 4, 8, 12, 16, 20, and 24, measuring changes in condition severity using a scoring system. Participants will also assess their own symptoms including oozing, bleeding, and pain on a scale from 0 to 10. The study will monitor quality of life and any changes in lesion size. Safety assessments include regular checks for side effects and blood tests to measure sirolimus levels. The treatment effects will be compared to usual care, which involves no active treatment.
Summary
The three ongoing trials for lymphatic malformation represent diverse approaches to treatment, with two trials focused on sirolimus (one oral, one topical) and one testing the novel agent RLY-2608. France hosts two of the three studies, both examining sirolimus in different formulations and for different locations of malformations. The international trial testing RLY-2608 spans three European countries (Belgium, Italy, and Spain), reflecting broader collaboration for this investigational medication targeting PIK3CA-related conditions.
The trials address different patient populations and malformation types: one focuses specifically on cervico-facial malformations in children with poor prognosis, another targets lingual (tongue) malformations in both children and adults, and the third addresses PIK3CA-related overgrowth spectrum in children and adolescents. The age ranges vary from as young as 1 year to adults, with the RLY-2608 trial limited to ages 2-17. Each study employs different assessment methods and timelines, from regular monitoring over 24 weeks to evaluations at therapeutic plateau points, reflecting the varying nature of these complex conditions.
