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Lymphatic MalformationPhase 2/3NCT06673290

Different Doses of Sirolimus for the Treatment of Cystic Lymphatic Malformations

A Phase 2/3 study testing Sirolimus (RAPAMUNE) in people with Lymphatic Malformation, run by West China Hospital at 1 site in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

The purpose of this study is to compare the efficacy and safety of different concentration gradients of sirolimus in the treatment of cystic lymphatic malformation. Read more about this study

Who is it for?
Ages 1 year to 18 years
Conditions the study is for
Lymphatic Malformation
What is being tested?
Sirolimus (RAPAMUNE)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
150 participants
Where
1 siteChina
Study dates
30 Nov 2024to 30 Dec 2026
Phase
Phase 2/3
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 1 year to 18 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Presenting a LM with the following characteristics:
  • Male and female;
  • Between 0 and 18 years of age;
  • LM diagnosis was confirmed by local investigators and by consensus of our multidisciplinary vascular anomaly group at the West China Hospital of Sichuan University based on:
  • Biopsy; Compatible MRI findings; History and clinical features.

Who cannot join

  • Patients contraindicated for the administration of sirolimus (e.g., those with an allergy to sirolimus or other rapamycin analog)
  • Exposure to chemotherapy, embolization, corticosteroids, propranolol, sclerotherapy or any other investigational agents within 1 weeks before enrolment on study;
  • Patients had a history of a major surgery within 2 weeks before enrollment;
  • Patients who have a history of treatment with sirolimus or other mTOR inhibitor;
  • Any known evidence of significant local or systemic uncontrolled infection, defined as receiving intravenous antibiotics at the time of enrollment;
  • Concurrent severe and/or uncontrolled medical diseases that could compromise participation in the study (e.g. uncontrolled diabetes, uncontrolled hypertension, severe malnutrition, chronic liver or renal disease, active upper gastrointestinal tract ulceration).
Show all 18Show fewer
  • Impairment of gastrointestinal function or chronic gastrointestinal disease that may significantly alter the absorption of sirolimus.
  • Patients with inadequate liver function:
  • Total bilirubin higher than or equal to 1.5 × the upper limit of the normal (ULN) for age and alanine aminotransferase and aspartate aminotransferase higher than or equal to 2.5 × the ULN for age.
  • Patients with inadequate renal function:
  • 0-5 years of age maximum serum creatinine (mg/dL) of 0.8; 6-10 years of age maximum serum creatinine (mg/dL) of 1.0; 11-14 years of age maximum serum creatinine (mg/dL) of 1.2;
  • Adequate bone marrow function:
  • Absolute neutrophil count lower than 1 × 109/L;
  • History of a malignancy within 5 years;
  • HIV infection or known immunodeficiency;
  • Indication for treatment with corticosteroids, vincristine, interferon-α, sirolimus, or tacrolimus for an indication other than IH;
  • Patients with an inability to participate in or follow-up during the study treatment and assessment plan;
  • Inability to give informed consent.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

China1 site, 1 recruiting

  • West China Hospital of Sichuan University

    Chengdu, Sichuan, 610041

    Yi Ji, professor, +86 028-85423453, jijiyuanyuan@163.com

    Jiangyuan Zhou, Doctor, +86 13668491160, 13668491160@163.com

    Recruiting

Other trials in China

About this study

The purpose of this study is to compare the efficacy and safety of different concentration gradients of sirolimus in the treatment of cystic lymphatic malformation.

Read the detailed description

Cystic lymphatic malformation is a disease caused by abnormal development of the lymphatic system, characterized by abnormal dilation and/or structural disorder of lymphatic vessels. These abnormalities may lead to accumulation of lymphatic fluid, causing local swelling, pain, and even affecting organ function. Cystic lymphatic malformation can occur anywhere in the body, including skin, soft tissue, internal organs, etc.

Sirolimus, also known as rapamycin, is an immunosuppressant mainly used to prevent rejection after organ transplantation. In recent years, studies have shown that sirolimus has certain potential in the treatment of lymphatic malformations.

However, long-term high-dose sirolimus treatment can cause some common complications, such as oral mucositis, which affects the quality of life of patients. More fine-grained control of rapamycin plasma concentrations may help improve the therapeutic effect and reduce the incidence of complications. Therefore, the investigators conducted this study to understand whether low-dose rapamycin is beneficial to the prognosis of patients.

Being tested
Sirolimus (RAPAMUNE)
Keywords
Lymphatic Malformation, sirolimus, Efficacy, Safety
Medical subject headings
Lymphatic Abnormalities

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Sirolimus (RAPAMUNE)Drug

    Also called Rapamycin, Rapamune

    Use of different doses of the same drug

Study groups in NCT06673290
Study groupRoleWhat they receive
Low dose of sirolimusExperimentalThe plasma trough concentration of sirolimus is maintained within the range of 5-8 ng/ml by adjusting sirolimus dose, for 1 year.
Receives: Drug: Sirolimus (RAPAMUNE)
High dose of sirolimusActive comparatorThe plasma trough concentration of sirolimus is maintained within the range of 10-15 ng/ml by adjusting sirolimus dose, for 1 year.
Receives: Drug: Sirolimus (RAPAMUNE)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The proportion of patients achieving an objective response at month 12

    Objective response was defined as ≥20% reduction in LM volume compared to that at baseline.

    Measured: 12 months

Secondary outcomes (5)

  1. The proportion of patients achieving an objective response at month 6

    Objective response was defined as ≥20% reduction in LM volume compared to that at baseline.

    Measured: 6 months

  2. lesion responses

    The primary endpoint was classified as follow: -Complete involution: 100% resolution of the measured LM; -Nearly complete involution was defined as decrease of ≥75% and <100%; -Partial involution was defined as decrease of ≥20% and <75%; -No change was defined as <20% increase and <20% decrease in the volumes of LM lesions; -Further growth was defined as ≥20% increase in the volume of index LM compared with the baseline volume measured. Lesion responses were overall lesion response rate and good lesion response rate. Overall lesion response comprised complete, nearly complete and partial involutions. Good lesion response comprised complete and nearly complete involutions.

    Measured: 6 and 12 months

  3. Quality of life (QOL) in patients

    Pediatric Quality of Life Inventory (PedsQLTM) 4.0 Genetic Core Infant Scales (<2 years) or Pediatric Quality of Life Inventory (PedsQLTM) 4.0 Genetic Core Scales (2-18 years) were used.

    Measured: 12 months

  4. Disease sequelae

    Disease sequelae were assessed by site investigators at month 12. The site investigators assessed patients' extremity swelling (if any), general physical activity and exercise levels.

    Measured: 12 months

  5. Frequency of adverse events

    Frequency of adverse events (e.g. gastrointestinal disorders, blood and lymphatic system disorders, metabolic disorders or other abnormal laboratory results, skin disorders and general disorders, etc.) collected by investigator and reported by parents. All adverse events were collected and graded according to Common Terminology Criteria for Adverse Events, version 5.0 (CTCAE v5.0). The causality of the adverse event was determined by the multidisciplinary staff and was classified as definitively not related, probably not related, possibly related, probably related, or definitively related. Any dose reductions, interruptions, or cessations enacted at the discretion of the investigators were recorded.

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Nov 2024
  2. Study start30 Nov 2024
  3. Primary completion30 Dec 2026 (estimated)
  4. Study completion30 Dec 2026 (estimated)

Resources

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 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
150 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06673290
Sponsor's protocol ID
RCT20241029
Status last verified
Dec 2024
First submitted
31 Oct 2024
Last updated
31 Dec 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Ghariani Fetoui N, Boussofara L, Gammoudi R, Belajouza C, Ghariani N, Denguezli M. Efficacy of sirolimus in the treatment of microcystic lymphatic malformation of the tongue. J Eur Acad Dermatol Venereol. 2019 Sep;33(9):e336-e337. doi: 10.1111/jdv.15628. Epub 2019 Apr 22. No abstract available.

    PubMed 30980684

  • Cai R, Yang X, Gu H, Chen H, Lin X. Comment on "Sirolimus for the treatment of verrucous venous malformation: A retrospective cohort study": Are we missing the lymphatic malformation component? J Am Acad Dermatol. 2023 Mar;88(3):e133-e134. doi: 10.1016/j.jaad.2018.08.050. Epub 2018 Sep 18. No abstract available.

    PubMed 30240774

  • Gu Y, Sebaratnam DF. Topical rapamycin and microcystic lymphatic malformations. J Am Acad Dermatol. 2024 Jan;90(1):e29-e30. doi: 10.1016/j.jaad.2023.06.066. Epub 2023 Sep 17. No abstract available.

    PubMed 37717734

  • Ozeki M, Endo S, Yasue S, Nozawa A, Asada R, Saito AM, Hashimoto H, Fujimura T, Yamada Y, Kuroda T, Ueno S, Watanabe S, Nosaka S, Miyasaka M, Umezawa A, Matsuoka K, Maekawa T, Hirakawa S, Furukawa T, Fumino S, Tajiri T, Takemoto J, Souzaki R, Kinoshita Y, Fujino A. Sirolimus treatment for intractable lymphatic anomalies: an open-label, single-arm, multicenter, prospective trial. Front Med (Lausanne). 2024 Feb 8;11:1335469. doi: 10.3389/fmed.2024.1335469. eCollection 2024.

    PubMed 38390569

  • Yonekura S, Komori T, Ishida Y, Kogame T, Kabashima K. Treatment With Topical Sirolimus for Recurrent Lymphatic Malformation of the External Urethral Meatus. JAMA Dermatol. 2022 Nov 1;158(11):1331-1332. doi: 10.1001/jamadermatol.2022.2793.

    PubMed 36044195

  • Strychowsky JE, Rahbar R, O'Hare MJ, Irace AL, Padua H, Trenor CC 3rd. Sirolimus as treatment for 19 patients with refractory cervicofacial lymphatic malformation. Laryngoscope. 2018 Jan;128(1):269-276. doi: 10.1002/lary.26780. Epub 2017 Aug 7.

    PubMed 28782106

  • Ozeki M, Fukao T. Generalized Lymphatic Anomaly and Gorham-Stout Disease: Overview and Recent Insights. Adv Wound Care (New Rochelle). 2019 Jun 1;8(6):230-245. doi: 10.1089/wound.2018.0850. Epub 2019 Jun 6.

    PubMed 31236308

  • Maruani A, Tavernier E, Boccara O, Mazereeuw-Hautier J, Leducq S, Bessis D, Guibaud L, Vabres P, Carmignac V, Mallet S, Barbarot S, Chiaverini C, Droitcourt C, Bursztejn AC, Lengelle C, Woillard JB, Herbreteau D, Le Touze A, Joly A, Leaute-Labreze C, Powell J, Bourgoin H, Gissot V, Giraudeau B, Morel B. Sirolimus (Rapamycin) for Slow-Flow Malformations in Children: The Observational-Phase Randomized Clinical PERFORMUS Trial. JAMA Dermatol. 2021 Nov 1;157(11):1289-1298. doi: 10.1001/jamadermatol.2021.3459.

    PubMed 34524406

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Sirolimus (RAPAMUNE) in people with Lymphatic Malformation, run by West China Hospital at 1 site in China.

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 5 inclusion and 18 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 31 Dec 2024. 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 China. 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.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

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?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The proportion of patients achieving an objective response at month 12 (time frame: 12 months). 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 NCT06673290, which also lists 8 linked publications.

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 31 Dec 2024.

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