Different Doses of Sirolimus for the Treatment of Cystic Lymphatic Malformations

NCT ID: NCT06673290

Last Updated: 2024-12-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2/PHASE3

Total Enrollment

150 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-11-30

Study Completion Date

2026-12-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Lymphatic Malformation

Keywords

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Lymphatic Malformation sirolimus Efficacy Safety

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Low dose of sirolimus

The plasma trough concentration of sirolimus is maintained within the range of 5-8 ng/ml by adjusting sirolimus dose, for 1 year.

Group Type EXPERIMENTAL

Sirolimus (RAPAMUNE)

Intervention Type DRUG

Use of different doses of the same drug

High dose of sirolimus

The plasma trough concentration of sirolimus is maintained within the range of 10-15 ng/ml by adjusting sirolimus dose, for 1 year.

Group Type ACTIVE_COMPARATOR

Sirolimus (RAPAMUNE)

Intervention Type DRUG

Use of different doses of the same drug

Interventions

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Sirolimus (RAPAMUNE)

Use of different doses of the same drug

Intervention Type DRUG

Other Intervention Names

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Rapamycin Rapamune

Eligibility Criteria

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Inclusion Criteria

* Presenting a LM with the following characteristics:

1. Male and female;
2. Between 0 and 18 years of age;
3. 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.

Exclusion Criteria

1. Patients contraindicated for the administration of sirolimus (e.g., those with an allergy to sirolimus or other rapamycin analog)
2. Exposure to chemotherapy, embolization, corticosteroids, propranolol, sclerotherapy or any other investigational agents within 1 weeks before enrolment on study;
3. Patients had a history of a major surgery within 2 weeks before enrollment;
4. Patients who have a history of treatment with sirolimus or other mTOR inhibitor;
5. Any known evidence of significant local or systemic uncontrolled infection, defined as receiving intravenous antibiotics at the time of enrollment;
6. 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).
7. Impairment of gastrointestinal function or chronic gastrointestinal disease that may significantly alter the absorption of sirolimus.
8. 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.
9. 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;
10. Adequate bone marrow function:

Absolute neutrophil count lower than 1 × 109/L;
11. History of a malignancy within 5 years;
12. HIV infection or known immunodeficiency;
13. Indication for treatment with corticosteroids, vincristine, interferon-α, sirolimus, or tacrolimus for an indication other than IH;
14. Patients with an inability to participate in or follow-up during the study treatment and assessment plan;
15. Inability to give informed consent.
Minimum Eligible Age

1 Year

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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West China Hospital

OTHER

Sponsor Role lead

Responsible Party

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Yi Ji

MD, PhD

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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West China Hospital of Sichuan University

Chengdu, Sichuan, China

Site Status RECRUITING

Countries

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China

Facility Contacts

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Yi Ji, professor

Role: primary

Jiangyuan Zhou, Doctor

Role: backup

Yi Ji

Role: backup

References

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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.

Reference Type BACKGROUND
PMID: 30980684 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30240774 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 37717734 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 38390569 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 36044195 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28782106 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31236308 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 34524406 (View on PubMed)

Other Identifiers

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RCT20241029

Identifier Type: -

Identifier Source: org_study_id