Intervention: Vincristine
Trial phase: Phase 2
ATC code: L01CA02
SMILES: CCC1(O)CC2CN(CCc3c([nH]c4ccccc34)C(C(=O)OC)(c3cc4c(cc3OC)N(C=O)C3C(O)(C(=O)OC)C(OC(C)=O)C5(CC)C=CCN6CCC43C65)C2)C1
Sex: All
Age groups: Child | Adult
Healthy volunteers: No
Participants at risk: 2
Group description: Induction phase: participants assigned to vincristine will receive vincristine weekly at a dose of 0.05mg/kg/dose IV (for participants less than 10kg) or a dose of 1.5 mg/m2/dose (for participants greater than 10kg) for 2 months.

Maintenance: if participants continue to receive vincristine weekly for 2 months, every 2 weeks for 5 months and every 3 weeks for 5 months.

Vincristine: Vincristine dose dependent upon weight. Weekly for 2 months (Induction); Weekly 2 months; every 2 weeks for next 5 months; every 3 weeks for 5 months (Maintenance)
Eligibility criteria:
Inclusion Criteria:

Diagnosis: All patients must have one of the following vascular anomalies as determined by clinical, radiologic and histologic criteria (when possible). Biopsy strongly recommended (but not required) with suggested immunostains: CD34, PROX-1 or D240, Glut-1 and MIB-1.

Kaposiform Hemangioendotheliomas
Tufted angioma

High Risk Stratification: In addition to the above diagnosis, all of the following criteria need to be met:

a. Kasabach Merritt Syndrome defined at a platelet counts less than 50,000 K/µl and/or fibrinogen level < 100 mg/dl at the time of diagnosis.

Age: Patients must be 0 - 31 years of age at the time of study entry. Enrollment includes patients of both genders and all ethnic groups.

Organ function requirements:

Adequate liver function defined as:

Total bilirubin ≤ 1.5 x ULN for age, and
SGPT (ALT) ≤ 5 x ULN for age, and
Serum albumin >/= 2 g/dL.
Fasting LDL cholesterol of <160 mg/dL
Fasting triglyceride <400 mg/dl

Adequate Bone Marrow Function defined as:

Peripheral absolute neutrophil count (ANC) >/= 1000/uL
Hemoglobin >/= 8.0 g/dL (may receive RBC transfusions)
No Platelet requirement

Adequate Renal Function Defined as:

A serum creatinine based on age as follows:

Age (Years) Maximum Serum Creatinine (mg/dL)

5 0.8 6 to ≤10 1.0 11 to ≤15 1.2 >15 1.5
Urine protein to creatinine ratio (UPC) < 0.3 g/l
Performance Status: Karnofsky >/= 50 (≥16 years of age) and Lansky >/= 50 for patients <16 years of age.

Prior therapy

Patients who have undergone surgical resection or interventional radiology procedures for disease control are eligible if they meet all inclusion criteria after surgery/procedure
Surgery: At least 2 weeks since undergoing any major surgery
Radiation: > 6 months from involved field radiation
Prior vincristine therapy is permitted. Patients may also have received up to 2 doses of vincristine prior to randomization.

Exclusion Criteria:

Concurrent severe and/or uncontrolled medical disease that could compromise participation in the study (e.g. uncontrolled diabetes, uncontrolled hypertension, severe infection, severe malnutrition, chronic liver or renal disease, active upper GI tract ulceration).
Patients who require medications that are strong inhibitors/inducers CYP3A4 enzyme activity, including anticonvulsants, (Appendix II) to control concurrent medical conditions are not eligible. Patients who discontinue use of prohibited medications with a one week washout prior to start of study treatment are eligible.
Known history of HIV seropositivity or known immunodeficiency. Testing is not required unless a condition is suspected.
Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of sirolimus (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection). A gastric tube or nasogastric tube is allowed.
Females who are pregnant or breast feeding.
Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method during the period they are receiving the study drug and for 3 months thereafter. Abstinence is an acceptable method of birth control. Females of childbearing potential will be given a pregnancy test within 7 days prior to administration of study treatment and must have a negative urine or serum pregnancy test.
Patients who have received prior treatment with an mTOR inhibitor.
Patients unwilling or unable to comply with the protocol or who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study.
Patients who currently have an uncontrolled infection, defined as receiving intravenous antibiotics.