Guided Discontinuation Versus Maintenance Treatment of Sirolimus in Pediatric Patients With Kaposiform Hemangioendothelioma

Fudan University

Status and phase: Completed; Phase 4

Conditions: Kasabach-Merritt Syndrome; Kaposiform Hemangioendothelioma

Treatments: Drug: Sirolimus

Study type: Interventional

Funder types: Other

Identifiers

NCT04448873

LK200421

Details and patient eligibility

About

This randomized controlled trial aims to compare guided discontinuation with maintenance treatment of sirolimus in pediatric patients with KHE.

Full description

Kaposiform Hemangioendothelioma (KHE) is a rare vascular tumor that occurs in infants and children. KHE is characterized by sheets of spindle cells with an infiltrative pattern in the dermis, subcutaneous fat, and muscle. It is locally aggressive and can cause Kasabach-Merritt phenomenon, a serious life-threatening coagulopathy characterized by profound thrombocytopenia and hypofibrinogenemia. Sirolimus, one of the mTOR inhibitors, has become a new and very effective treatment, which is especially reliable for KHE with KMP and has acceptable side effects. However, there is yet no strong evidence on the best practice of treatment length of sirolimus. This randomized controlled trial aims to compare guided discontinuation with maintenance treatment in pediatric patients with KHE in order to provide a basis for the optimal treatment duration of sirolimus, as well as the clinical characteristics of pediatric patients who can safely reduce the dose till withdrawal.

Enrollment: 30 patients

Sex: All

Ages: Under 12 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participant diagnosed with KHE with or without KMP
• Participant age 0-12 years
• Participant with detailed medical records of the disease at the time of screening
• Participant with at least two years of remission of KHE and no previous toxicity or adverse events
• Participant with normal liver and kidney function
• Participant with signed and dated informed consent from the guardian(s)

Exclusion criteria

• Participant with other hematological diseases
• Participant with other solid tumor
• Participant with general disease such as hypertension, diabetes, adrenal insufficiency, neurological diseases, liver and kidney dysfunction, and cardiopulmonary insufficiency.
• Participant with infectious diseases
• Unwilling participant

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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30 participants in 2 patient groups

Maintenance treatment group

Active Comparator group

Description:

After at least 2 years of remission of KHE, the participant receives sirolimus as usual. The serum concentration is supposed to be 5-7 ng/ml. If the effect or side effects of sirolimus require discontinuation, it is allowed to modify intervention, and if so, the patient stays in the maintenance group.

Treatment:

Drug: Sirolimus

Guided discontinuation group

Experimental group

Description:

After at least 2 years of remission of KHE, the discontinuation measurement should be guided by the clinician with the following principles: 1. 10% monthly reduction of the previous dose at most. 2. At least 5 half-lives between each reduction (2 weeks). 3. Blood concentration should be monitored monthly. Adjustment can be suggested according to the linear relationship between the dose and the blood concentration. 4. At least 6 months for the duration of guided discontinuation. 5. Regular assessments and evaluations should be done. If the condition relapses or worsens during this process, dose of sirolimus should be adjusted to the previously effective dose. After a 3-month stabilization phase, 5% monthly reduction of the previous dose could be considered.

Treatment:

Drug: Sirolimus