Safety and Efficacy of Low-dose Sirolimus to Kaposiform Hemangioendothelioma

NCT ID: NCT04077515

Last Updated: 2023-01-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 92 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-01
• Study Completion Date: 2022-12-31

Brief Summary

to evaluate the safety and efficacy of Low-dose sirolimus in Kaposiform Hemangioendothelioma in Chinese children by a prospective, randomized open trial.

Detailed Description

The clinically commonly used dose of sirolimus for Kaposiform Hemangioendothelioma is 0.8 mg/m2 administered twice daily, and the blood concentration can be maintained at 10-15 ng/ml according to the pharmacokinetic formula.Related research reports that maintaining low blood concentration of sirolimus is effective in the treatment of certain vascular malformations and hemangioma, and complications are less. In the clinical practice, we found that the blood concentration was maintained at 7-10 ng/ml, and the patients still achieved good results and the chance of infections decreased. Therefore, this clinical trial was designed.In this trial, two different dosing regimens with corresponding blood concentration were designed to compare the safety and efficacy.In the high concentration group, the sirolimus dosage was adjusted monthly to achieve trough levels between 10 and 15 ng/mL(excluding 10 ng/ml), and it is still used at 0.8 mg/m2 administered twice daily.The low concentration group is 7-10 ng/ml (including 10 ng/ml), and the initial use of sirolimus is 0.7mg/m2 administered twice daily.The dose was adjusted according to the formula after two weeks.The follow-up and evaluation were performed according to a strictly established follow-up schedule after taking the drug.

Conditions

Hemangioma; Kaposiform Hemangioendothelioma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

high blood concentration group

The blood concentration is maintained at 10-15ng/ml (not including 10ng/ml).

Group Type: ACTIVE_COMPARATOR

Sirolimus(0.8mg/m2)

Intervention Type: DRUG

The initial use of sirolimus is 0.8mg/m2 administered twice daily.After two weeks of taking the drug, blood concentrations are measured and adjusted appropriately to maintain the targeted blood concentration.

low blood concentration group

The blood concentration is maintained at 7-10ng/ml (including 10ng/ml).

Group Type: EXPERIMENTAL

Sirolimus(0.7mg/m2)

Intervention Type: DRUG

The initial use of sirolimus is 0.7mg/m2 administered twice daily.After two weeks of taking the drug, blood concentrations are measured and adjusted appropriately to maintain the targeted blood concentration.

Interventions

Sirolimus(0.8mg/m2)

The initial use of sirolimus is 0.8mg/m2 administered twice daily.After two weeks of taking the drug, blood concentrations are measured and adjusted appropriately to maintain the targeted blood concentration.

Intervention Type: DRUG

Sirolimus(0.7mg/m2)

The initial use of sirolimus is 0.7mg/m2 administered twice daily.After two weeks of taking the drug, blood concentrations are measured and adjusted appropriately to maintain the targeted blood concentration.

Intervention Type: DRUG

Other Intervention Names

Rapamycin; Rapamycin

Eligibility Criteria

Inclusion Criteria

• Kaposiform Hemangioendotheliomas with or without Kasabach-Merritt Phenomenon.
• 0 - 12 years of age at the time of study entry.
• Male or female.
• Consent of parents (or the person having parental authority in families): Signed and dated written informed consent.

Exclusion Criteria

• with hematological diseases.
• with other solid tumors.
• with hypertension, diabetes, adrenal insufficiency, neurological diseases, liver and kidney dysfunction, and cardiopulmonary insufficiency.
• with tuberculosis,cytomegalovirus and Epstein-Barr virus infection before the treatment.

• Maximum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Children's Hospital of Fudan University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kai Li, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Fudan University

Locations

Children's Hospital of Fudan University

Shanghai, , China

Countries

China

References

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.

Reference Type: BACKGROUND

PMID: 23796341 (View on PubMed)

Yoon HY, Hwang JJ, Kim DS, Song JW. Efficacy and safety of low-dose Sirolimus in Lymphangioleiomyomatosis. Orphanet J Rare Dis. 2018 Nov 14;13(1):204. doi: 10.1186/s13023-018-0946-8.

Reference Type: BACKGROUND

PMID: 30428897 (View on PubMed)

Kazmierczak D, Maliszewska A. [Disturbances of tooth and maxillary development in Down's syndrome and their treatment]. Czas Stomatol. 1986 Nov;39(11):755-9. No abstract available. Polish.

Reference Type: BACKGROUND

PMID: 2958244 (View on PubMed)

Ozgonenel B, Martin A. Low-dose sirolimus controls recurrent iron deficiency in a patient with blue rubber bleb nevus syndrome. Pediatr Blood Cancer. 2015 Nov;62(11):2054-5. doi: 10.1002/pbc.25590. Epub 2015 Jul 1. No abstract available.

Reference Type: BACKGROUND

PMID: 26132912 (View on PubMed)

Other Identifiers

2019-161

Identifier Type: -

Identifier Source: org_study_id