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

September 24, 2023 updated by: Children's Hospital of Fudan University

Guided Discontinuation Versus Maintenance Treatment of Sirolimus in Pediatric Patients With Kaposiform Hemangioendothelioma: a Randomized Controlled Trial

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

Study Overview

Status

Completed

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Shanghai
      • Shanghai, Shanghai, China, 210012
        • Children's Hospital of Fudan University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 12 years (Child)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Maintenance treatment group
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.
After at least 2 years of remission of KHE, we compare guided discontinuation with maintenance treatment in pediatric patients with KHE.
Other Names:
  • Rapamycin
Experimental: Guided discontinuation group

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.

After at least 2 years of remission of KHE, we compare guided discontinuation with maintenance treatment in pediatric patients with KHE.
Other Names:
  • Rapamycin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Remission of KHE and no use of sirolimus at one year follow-up.
Time Frame: From admission to follow-up one year
The primary outcome is a binary variable. The primary outcome measure will be analyzed with binary logistic regression to estimate the odds ratio between the two groups.
From admission to follow-up one year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Remission of KHE and the dose of sirolimus at one year follow-up
Time Frame: From admission to follow-up one year
At one year's follow-up, the participant may be on remission, but still taking sirolimus. The condition is a binary variable and the dose of sirolimus is a continuous variable.
From admission to follow-up one year
Relapse of KHE and the dose of sirolimus at one year follow-up
Time Frame: From admission to follow-up one year
At one year's follow-up, the participant may suffer from relapse of KHE and still takes sirolimus. The period of time to the first relapse will be recorded as a time variable, and the cox regression survival analysis model will be used.The dose of sirolimus is a continuous variable. Whether this variable is normally distributed will be checked.
From admission to follow-up one year
Side effects of sirolimus
Time Frame: From admission to follow-up one year
The outcome 4 will be described. Adverse events will be reported according to Common Terminology Criteria for Adverse Events, version 4.0 (CTCAE v4.0). Incidence of complications such as oral ulcers, abnormal liver enzymes, infections will be recorded. The blood concentration of sirolimus will be adjusted accordingly.
From admission to follow-up one year
Platelet count
Time Frame: From admission to follow-up one year
Platelet count is one of the major indicators of response to treatment and will be used in a prognosis model to predict the clinical characteristics of patients with benefits. It is supposed to be greater than 100×10^9/L.
From admission to follow-up one year
Fibrinogen level
Time Frame: From admission to follow-up one year
Fibrinogen level will be used in a prognosis model to predict the clinical characteristics of patients with benefits. It is supposed to be at 2-4g/L.
From admission to follow-up one year
Tumor volume
Time Frame: From admission to follow-up one year
Tumor volume will be used in a prognosis model to predict the clinical characteristics of patients with benefits. The size of the tumor is supposed to shrink according to imaging evaluation. The tumor is supposed to be softer by palpation.
From admission to follow-up one year
Complaints
Time Frame: From admission to follow-up one year
Complaints are subjective feelings. Whether there is pain, swelling, lameness or skin color change will be recorded as binary variables and used in a prognosis model to predict the clinical characteristics of patients with benefits.
From admission to follow-up one year

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Remission of KHE and no use of sirolimus at two or three year follow-up
Time Frame: From admission to follow-up two and three years
This outcome is a binary variable. The primary outcome measure will be analyzed with binary logistic regression to estimate the odds ratio between the two groups.
From admission to follow-up two and three years
Remission of KHE and the dose of sirolimus at two or three year follow-up
Time Frame: From admission to follow-up two and three years
At two or three years' follow-up, the participant may be on remission, but still taking sirolimus. The condition is a binary variable and the dose of sirolimus is a continuous variable.
From admission to follow-up two and three years
Relapse of KHE and the dose of sirolimus at two or three year follow-up
Time Frame: From admission to follow-up two and three years
At two or three years' follow-up, the participant may suffer from relapse of KHE and still takes sirolimus. The period of time to the relapse will be recorded as a time variable, and the cox regression survival analysis model will be used.The dose of sirolimus is a continuous variable. Whether this variable is normally distributed will be checked.
From admission to follow-up two and three years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Kai Li, MD, PhD, Children's Hospital of Fudan University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2020

Primary Completion (Actual)

February 1, 2023

Study Completion (Actual)

July 1, 2023

Study Registration Dates

First Submitted

May 10, 2020

First Submitted That Met QC Criteria

June 24, 2020

First Posted (Actual)

June 26, 2020

Study Record Updates

Last Update Posted (Actual)

September 26, 2023

Last Update Submitted That Met QC Criteria

September 24, 2023

Last Verified

September 1, 2023

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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