Different Doses of Sirolimus for the Treatment of Cystic Lymphatic Malformations

NCT06673290 | Recruiting Phase 2 DMC

• 1 other identifier: RCT20241029
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Lymphatic Malformation

Keywords

Lymphatic Malformation; sirolimus; Efficacy; Safety

Outcome Measures

Primary Outcomes (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.

  12 months

Secondary Outcomes (5)

• The proportion of patients achieving an objective response at month 6

  6 months

• lesion responses

  6 and 12 months

• Quality of life (QOL) in patients

  12 months

• Disease sequelae

  12 months

• Frequency of adverse events

  12 months

Study Arms (2)

Low dose of sirolimus

EXPERIMENTAL

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

Drug: Sirolimus (RAPAMUNE)

High dose of sirolimus

ACTIVE COMPARATOR

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

Drug: Sirolimus (RAPAMUNE)

Interventions

Sirolimus (RAPAMUNE) DRUG

Use of different doses of the same drug

Also known as: Rapamycin, Rapamune

High dose of sirolimus; Low dose of sirolimus

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• 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:
• 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;

Sponsors & Collaborators

• West China Hospital: lead

Study Sites (1)

West China Hospital of Sichuan University

Chengdu, Sichuan, 610041, China

RECRUITING

Related Publications (8)

• 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.

  PMID: 30980684 BACKGROUND

• 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.

  PMID: 30240774 BACKGROUND

• 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.

  PMID: 37717734 BACKGROUND

• 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.

  PMID: 38390569 BACKGROUND

• 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.

  PMID: 36044195 BACKGROUND

• 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.

  PMID: 28782106 BACKGROUND

• 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.

  PMID: 31236308 BACKGROUND

• 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.

  PMID: 34524406 BACKGROUND

MeSH Terms

Conditions

Lymphatic Abnormalities

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Lymphatic Diseases; Hemic and Lymphatic Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: October 31, 2024
• First Posted: November 4, 2024
• Study Start: November 30, 2024
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: December 31, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)