Efficacy and Safety of Different Concentrations of Sirolimus in the Treatment of Kaposiform Hemangioendothelioma.

NCT04775173 | Completed Phase 2 DMC

• 1 other identifier: 2021-217
• Study Type: interventional
• Target: 79
• 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 Kaposiform hemangioendothelioma.

Conditions

Kaposiform Hemangioendothelioma

Keywords

Kaposiform Hemangioendothelioma; 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 KHE volume compared to that at baseline.

  12 months

Secondary Outcomes (5)

• lesion responses

  12 months

• Quality of life (QOL) in patients

  12 months

• Disease sequelae

  12 months

• Frequency of adverse events

  12 months

• The changes of fibrinogen and D-dimer levels

  12 months

Study Arms (2)

Low dose of sirolimus

EXPERIMENTAL

Sirolimus 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

High dose of sirolimus

ACTIVE COMPARATOR

Sirolimus 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

Interventions

Sirolimus 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 Day - 14 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Presenting a KHE with the following characteristics:
• Male and female;
• Between 0 and 14 years of age;
• KHE 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.
• The multidisciplinary vascular anomaly group was a collaboration team that included vascular anomaly experts in pediatric surgery, plastic surgery, pediatric dermatology, pathology and radiology.
• Without KMP, which was defined as a platelet count of less than 100×10\^9/L, with consumptive coagulopathy and hypofibrinogenemia.
• Patients were required to have adequate liver, renal and bone marrow function, and absence of active infection
• Consent of parents (or the person with parental authority in families): signed and dated written informed consent.

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

Location

Related Publications (7)

• Ji Y, Chen S, Yang K, Xia C, Li L. Kaposiform hemangioendothelioma: current knowledge and future perspectives. Orphanet J Rare Dis. 2020 Feb 3;15(1):39. doi: 10.1186/s13023-020-1320-1.

  PMID: 32014025 RESULT

• Ji Y, Chen S, Xiang B, Li K, Xu Z, Yao W, Lu G, Liu X, Xia C, Wang Q, Li Y, Wang C, Yang K, Yang G, Tang X, Xu T, Wu H. Sirolimus for the treatment of progressive kaposiform hemangioendothelioma: A multicenter retrospective study. Int J Cancer. 2017 Aug 15;141(4):848-855. doi: 10.1002/ijc.30775. Epub 2017 May 26.

  PMID: 28486787 RESULT

• Zhang G, Chen H, Gao Y, Liu Y, Wang J, Liu XY. Sirolimus for treatment of Kaposiform haemangioendothelioma with Kasabach-Merritt phenomenon: a retrospective cohort study. Br J Dermatol. 2018 May;178(5):1213-1214. doi: 10.1111/bjd.16400. Epub 2018 Mar 25. No abstract available.

  PMID: 29388191 RESULT

• Wang Z, Yao W, Sun H, Dong K, Ma Y, Chen L, Zheng S, Li K. Sirolimus therapy for kaposiform hemangioendothelioma with long-term follow-up. J Dermatol. 2019 Nov;46(11):956-961. doi: 10.1111/1346-8138.15076. Epub 2019 Sep 5.

  PMID: 31489702 RESULT

• Johnson AB, Richter GT. Vascular Anomalies. Clin Perinatol. 2018 Dec;45(4):737-749. doi: 10.1016/j.clp.2018.07.010. Epub 2018 Sep 18.

  PMID: 30396415 RESULT

• Adams DM, Ricci KW. Vascular Anomalies: Diagnosis of Complicated Anomalies and New Medical Treatment Options. Hematol Oncol Clin North Am. 2019 Jun;33(3):455-470. doi: 10.1016/j.hoc.2019.01.011.

  PMID: 31030813 RESULT

• Drolet BA, Trenor CC 3rd, Brandao LR, Chiu YE, Chun RH, Dasgupta R, Garzon MC, Hammill AM, Johnson CM, Tlougan B, Blei F, David M, Elluru R, Frieden IJ, Friedlander SF, Iacobas I, Jensen JN, King DM, Lee MT, Nelson S, Patel M, Pope E, Powell J, Seefeldt M, Siegel DH, Kelly M, Adams DM. Consensus-derived practice standards plan for complicated Kaposiform hemangioendothelioma. J Pediatr. 2013 Jul;163(1):285-91. doi: 10.1016/j.jpeds.2013.03.080. No abstract available.

  PMID: 23796341 RESULT

MeSH Terms

Conditions

Kaposiform Hemangioendothelioma

Interventions

Sirolimus

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Yi Ji, MD, PhD

  West China Hospital

  PRINCIPAL INVESTIGATOR

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: Clinical Professor

Study Record Dates

• First Submitted: February 19, 2021
• First Posted: March 1, 2021
• Study Start: February 17, 2021
• Primary Completion: August 10, 2023
• Study Completion: August 10, 2023
• Last Updated: May 7, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)