Kaposiform Hemangioendothelioma, Kasabach-Merritt Syndrome
Conditions
Keywords
Kaposiform Hemangioendothelioma, Kasabach-Merritt Syndrome, Sirolimus, Rapamycin
Brief summary
This randomized controlled trial aims to compare guided discontinuation with maintenance treatment of sirolimus in pediatric patients with KHE.
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.
Interventions
DRUGSirolimus
After at least 2 years of remission of KHE, we compare guided discontinuation with maintenance treatment in pediatric patients with KHE.
Sponsors
Children's Hospital of Fudan University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Only the outcome assessors are blinded, neither clinicians nor patients, because they should be attentive of the risk of relapse in the discontinuation group. Also, it seems unethical if researchers were not to discover the group of patients in the maintenance group who can discontinue sirolimus without relapsing. Clinicians should be given the possibility to adjust dose and ensure the benefits of patients. Therefore, this trial only includes assessors blinding.
Eligibility
Sex/Gender
ALL
Age
No minimum to 12 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Remission of KHE and no use of sirolimus at one year follow-up. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Side effects of sirolimus | 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. |
| Fibrinogen level | 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. |
| Tumor volume | 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. |
| Complaints | 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. |
| Remission of KHE and the dose of sirolimus at one year follow-up | 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. |
| Relapse of KHE and the dose of sirolimus at one year follow-up | 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. |
| Platelet count | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Relapse of KHE and the dose of sirolimus at two or three year follow-up | 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. |
| Remission of KHE and no use of sirolimus at two or three year follow-up | 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. |
| Remission of KHE and the dose of sirolimus at two or three year follow-up | 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. |
Countries
China
Outcome results
None listed