Sirolimus Versus Sirolimus Plus Prednisolone for Kaposiform Hemangioendothelioma

NCT03188068 | Completed Phase 2 DMC

• 4 other identifiers: 2017-31281401606814008622015SU04A15
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Kaposiform hemangioendothelioma (KHE) is a rare vascular neoplasm that occurs predominantly in infancy or early childhood. KHE has a nearly equal sex ratio. The annual incidence of KHE has been estimated at 0.071 per 100,000 children. KHE presents with intermediate-malignant and locally aggressive characteristics but without distant metastases. This pilot trial studies sirolimus versus sirolimus plus pednisolone in treating patients diagnosed with kaposiform hemangioendothelioma (KHE) and Kasabach-Merritt phenomemon (KMP) that cannot be removed by surgery. The purpose of this study is to compare the efficacy and safety of orally administered sirolimus versus sirolimus plus pednisolone in the treatment of KHE associated with KMP.

Conditions

Kaposiform Hemangioendothelioma; Kasabach Merritt Phenomenon

Keywords

Kaposiform Hemangioendothelioma; Kasabach Merritt Phenomenon; Sirolimus; Prednisolone

Outcome Measures

Primary Outcomes (4)

• The changes of platelet counts

  Platelet counts

  2 months

• The changes of fibrinogen levels

  Fibrinogen levels

  2 months

• The changes in KHE volume

  Response to therapy was measured by volumetric magnetic resonance imaging (MRI) analyses were performed at baseline and 6 and 12 months after treatment and were independently assessed by 2 radiologists. Changes in KHE size were classified as further growth (increase of ≥10%), no change (\<10% increase and \<10% decrease), partial involution (decrease of ≥10% and \<75%), nearly complete involution (decrease of ≥75% and \<100%), or complete involution (100%). Photographs of the mixed KHE were taken at months 0, 6 and 12 by a medical photographer.

  6 and 12 months

• The changes in the patient's symptoms and/or complications.

  Improvement in the range of motion.

  6 and 12 months

Secondary Outcomes (4)

• Frequency of adverse events

  12 months

• Change in blood biomarkers

  6 and 12 months

• Quality of life (QOL) in patients.

  12 months

• Measuring the impact of KHE on family functioning.

  12 months

Study Arms (2)

Sirolimus

ACTIVE COMPARATOR

Sirolimus was initiated at a dosage of 0.8 mg/m2 administered twice daily. Subsequently, the sirolimus dosage was adjusted monthly to achieve trough levels between 10 and 15 ng/mL.

Drug: Sirolimus

Sirolimus plus prednisolone

ACTIVE COMPARATOR

Sirolimus was initiated at a dosage of 0.8 mg/m2 administered twice daily. Subsequently, the sirolimus dosage was adjusted monthly to achieve trough levels between 10 and 15 ng/mL. Prednisolone was administered 2 mg/kg administered once daily. Should satisfactory clinical responses and hematologic stabilization ensue, prednisolone may be tapered and discontinued within the following 4-6 weeks.

Drug: Sirolimus; Drug: Prednisolone

Interventions

Sirolimus DRUG

Oral administration

Also known as: Rapamycin

Sirolimus; Sirolimus plus prednisolone

Prednisolone DRUG

Oral administered with sirolimus

Sirolimus plus prednisolone

Eligibility Criteria

• Age: 1 Day - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Presenting a KHE with the following characteristics:
• Clinical features and histological findings consistent with progressive, non-resectable KHE associated with KMP.
• Patients must be 0 - 18 years of age at the time of study entry.
• Without functional impairment requiring treatment of corticosteroid.
• Organ function requirements:
• Adequate liver function:
• Total bilirubin less than or equal to 1.5 x upper limit of normal (ULN)for age, and
• ALT and AST less than or equal to 2.5 x upper limit normal (ULN) for age.
• Adequate renal function:
• years of age maximum serum creatinine (mg/dL) of 0.8
• years of age maximum serum creatinine (mg/dL) of 1.0
• years of age maximum serum creatinine (mg/dL) of 1.2
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• West China Hospital: lead

Study Sites (1)

West China Hospital of Sichuan University

Chengdu, Sichuan, 610041, China

Location

Related Publications (6)

• Ji Y, Chen S, Xiang B, Li K, Xu Z, Yao W, Lu G, Liu X, Xia C, Wang Q, Li Y, Wang C, Yang K, Yang G, Tang X, Xu T, Wu H. Sirolimus for the treatment of progressive kaposiform hemangioendothelioma: A multicenter retrospective study. Int J Cancer. 2017 Aug 15;141(4):848-855. doi: 10.1002/ijc.30775. Epub 2017 May 26.

  PMID: 28486787 BACKGROUND

• Wang C, Li Y, Xiang B, Li F, Chen S, Li L, Ji Y. Successful Management of Pancreatic Kaposiform Hemangioendothelioma With Sirolimus: Case Report and Literature Review. Pancreas. 2017 May/Jun;46(5):e39-e41. doi: 10.1097/MPA.0000000000000801. No abstract available.

  PMID: 28426496 BACKGROUND

• Reichel A, Hamm H, Wiegering V, Wiewrodt B, Neubauer H, Ernestus K, Winkler B. Kaposiform hemangioendothelioma with Kasabach-Merritt syndrome: successful treatment with sirolimus. J Dtsch Dermatol Ges. 2017 Mar;15(3):329-331. doi: 10.1111/ddg.12987. Epub 2017 Feb 21. No abstract available.

  PMID: 28220608 BACKGROUND

• Alaqeel AM, Alfurayh NA, Alhedyani AA, Alajlan SM. Sirolimus for treatment of kaposiform hemangioendothelioma associated with Kasabach-Merritt phenomenon. JAAD Case Rep. 2016 Dec 5;2(6):457-461. doi: 10.1016/j.jdcr.2016.06.005. eCollection 2016 Nov. No abstract available.

  PMID: 27981218 BACKGROUND

• Mahajan P, Margolin J, Iacobas I. Kasabach-Merritt Phenomenon: Classic Presentation and Management Options. Clin Med Insights Blood Disord. 2017 Mar 16;10:1179545X17699849. doi: 10.1177/1179545X17699849. eCollection 2017.

  PMID: 28579853 BACKGROUND

• Ji Y, Chen S, Zhou J, Yang K, Zhang X, Xiang B, Qiu T, Gong X, Zhang Z, Lan Y, Hu F, Kong F, Qiu Q, Zhang Y. Sirolimus plus prednisolone vs sirolimus monotherapy for kaposiform hemangioendothelioma: a randomized clinical trial. Blood. 2022 Mar 17;139(11):1619-1630. doi: 10.1182/blood.2021014027.

  PMID: 35030255 DERIVED

MeSH Terms

Conditions

Kaposiform Hemangioendothelioma; Kasabach-Merritt Syndrome

Interventions

Sirolimus; Prednisolone

Condition Hierarchy (Ancestors)

Hemangioma; Neoplasms, Vascular Tissue; Neoplasms by Histologic Type; Neoplasms; Thrombocytopenia; Blood Platelet Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Cytopenia

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Yi Ji, MD, PhD

  West China Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 9, 2017
• First Posted: June 15, 2017
• Study Start: June 1, 2017
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2021
• Last Updated: April 21, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)