Clinical trial NCT04077515: Safety and Efficacy of Low-dose Sirolimus to Kaposiform Hemangioendothelioma
Official title: Safety and Efficacy of Low-dose Sirolimus to Kaposiform Hemangioendothelioma:A Prospective, Randomized Open Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hemangioma
Kaposiform Hemangioendothelioma
Keywords: Kaposiform Hemangioendothelioma
Kasabach-Merritt Syndrome
Sirolimus
Rapamycin
Lead sponsor: Children's Hospital of Fudan University
Sponsor class: OTHER
First posted: 2019-09-04
Enrollment: 92
Sex: ALL
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: response to treatment
timeFrame: 1 year after taking the drug
Secondary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: 1 year after taking the drug
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Children's Hospital of Fudan University
Study officials:
affiliation: Children's Hospital of Fudan University
name: Kai Li, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.