Low- vs High-Dose Sirolimus With Prednisolone for KHE and KMP

This randomized clinical trial evaluates if low-dose sirolimus (target trough 4-8 ng/mL) combined with prednisolone is noninferior in efficacy but superior in safety compared to standard high-dose sirolimus (target trough 10-15 ng/mL) combined with prednisolone in pediatric patients with kaposiform hemangioendothelioma and Kasabach-Merritt phenomenon (KHE with KMP), with participants randomized 1:1 to receive the assigned regimen, undergo routine blood and imaging monitoring, and be evaluated for clinical response and adverse events.

Sex

All

Minimum age

1 Day

Maximum age

18 Years

Inclusion Criteria:

* Presenting a KHE with the following characteristics:

  1. Clinical features and histological findings consistent with progressive, non-resectable KHE associated with KMP.
  2. Patients must be 0 - 18 years of age at the time of study entry.
  3. Without functional impairment requiring treatment of corticosteroid.
* Organ function requirements:

  1 Adequate liver function:
  1. Total bilirubin less than or equal to 1.5 x upper limit of normal (ULN)for age, and
  2. ALT and AST less than or equal to 2.5 x upper limit normal (ULN) for age.

  2 Adequate renal function:
  1. 0-5 years of age maximum serum creatinine (mg/dL) of 0.8
  2. 6-10 years of age maximum serum creatinine (mg/dL) of 1.0
  3. 11-15 years of age maximum serum creatinine (mg/dL) of 1.2
  4. 16-18 years of age maximum serum creatinine (mg/dL) of 1.5
* Adequate bone marrow function: Absolute Neutrophil Count (ANC) greater than or equal to 1 x 10 to the ninth/Liter.
* Consent of parents (or the person having parental authority in families): Signed and dated written informed consent.

Exclusion Criteria:

* Allergy to sirolimus or other rapamycin analogues.
* Any known evidence of significant local or systemic uncontrolled infection, defined as receiving intravenous antibiotics at the time of randomization.
* Patients must not be known to be Human Immunodeficiency Virus positive or known immunodeficiency. Testing is not required unless a condition is suspected.
* Other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study (e.g. uncontrolled diabetes, uncontrolled hypertension, severe malnutrition, chronic liver or renal disease, active upper gastrointestinal tract ulceration).
* Impairment of gastrointestinal function or chronic gastrointestinal disease that may significantly alter the absorption of sirolimus.
* Patients who have a history of malignancy.
* Patients with an inability to participate or to follow the study treatment and assessment plan.

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