Safety and Efficacy Study of Sirolimus in Complicated Vascular Anomalies

NCT00975819 | Completed Phase 2 Results DMC

• 2 other identifiers: SIR-DA-09015R01FD003712-04
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to determine if the use of sirolimus in the treatment of children and young adults with complicated vascular anomalies will prove to be safe and provide objective response resulting in improved clinical status and quality of life. Funding Source - FDA OOPD (Food and Drug Administration - Office of Orphan Products Development)

Conditions

Kaposiform Hemangioendotheliomas; Tufted Angioma; Capillary Venous Lymphatic Malformation; Venous Lymphatic Malformation; Microcystic Lymphatic Malformation; Mucocutaneous Lymphangiomatosis and Thrombocytopenia; Capillary Lymphatic Arterial Venous Malformations; PTEN Overgrowth Syndrome With Vascular Anomaly; Lymphangiectasia Syndromes

Outcome Measures

Primary Outcomes (2)

• Overall Response by Radiologic Evaluation, Quality of Life Assessment, and Functional Impairment Score

  Measures were determined by 3 distinct methods: radiologic evaluation, functional impairment score (clinical measurement of disease), and health-related quality of life. (HRQOL). The most common radiologic evaluation was MRI but other studies including CT and X-rays were included. HRQOL was assessed using the Pediatric Quality of Life Inventory 4.0 (3-18 years) ad infant Scales (\< or = to 2 years) and the Functional Assessment of Chronic Illness System (\> 18 years). Third method was the functional impairment score which was adopted from the measure of organ function that have been validated in the quantification of adverse even results from medical therapies and procedures. Patients needed to have complete response, normalization in quality of life and functional impairment score to have a complete response. In order to have a partial response they needed to have improvement in all three areas of assessment and not worsening of any others.

  6 months

• Overall Response by Radiologic Evaluation, Quality of Life Assessment, and Functional Impairment Score

  Measures were determined by 3 distinct methods: radiologic evaluation, functional impairment score (clinical measurement of disease), and health-related quality of life. (HRQOL). The most common radiologic evaluation was MRI but other studies including CT and X-rays were included. HRQOL was assessed using the Pediatric Quality of Life Inventory 4.0 (3-18 years) ad infant Scales (\< or = to 2 years) and the Functional Assessment of Chronic Illness System (\> 18 years). Third method was the functional impairment score which was adopted from the measure of organ function that have been validated in the quantification of adverse even results from medical therapies and procedures. Patients needed to have complete response, normalization in quality of life and functional impairment score to have a complete response. In order to have a partial response they needed to have improvement in all three areas of assessment and not worsening of any others.

  12 months

Study Arms (1)

Sirolimus

EXPERIMENTAL

Single arm using Sirolimus 0.8 mg/m2 per dose twice daily, Liquid form (1mg/ml) Length: 12 cycles of 28 day cycles

Drug: sirolimus

Interventions

sirolimus DRUG

liquid dosing based on trough levels

Also known as: Rapamune, rapamycin

Sirolimus

Eligibility Criteria

• Age: Up to 31 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosis: All patients must have one of the following vascular anomalies as determined by clinical, radiographic and histologic criteria (when possible):
• Kaposiform Hemangioendotheliomas with Kasabach-Merritt Phenomenon
• Kaposiform Hemangioendotheliomas without Kasabach-Merritt Phenomenon
• Tufted Angioma with Kasabach-Merritt Phenomenon
• Tufted Angioma without Kasabach-Merritt Phenomenon
• Capillary Lymphatico-Venous Malformation (CLVM)
• Venous Lymphatic Malformation (VLM)
• Microcystic Lymphatic Malformation (MLM)
• Multifocal Lymphangiomatosis and Thrombocytopenia (MLT)/Cutaneovisceral Angiomatosis and Thrombocytopenia (CAT)
• Capillary Lymphatic Arterial Venous Malformations (CLAVM)
• PTEN Overgrowth syndrome with vascular anomaly
• Lymphangiectasia Syndromes
• If archived tissue is available, histological diagnosis will be confirmed by the pathology lab at the enrolling site.
• Complications: Patients must have vascular anomalies that have potential to cause significant morbidity. In addition to the above diagnosis, one or more of the following criteria needs to be met:
• Coagulopathy

You may not qualify if:

• Dental braces or prosthesis only if it interferes with radiologic analysis of vascular anomaly.
• Concurrent severe and/or uncontrolled medical disease which 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).
• Chronic treatment with systemic steroids or another immunosuppressive agent. Patients with endocrine deficiencies are allowed to receive physiologic or stress doses of steroids if necessary. Patients with the diagnosis of a vascular tumor (KHE, TA) can be on a weaning dose of steroids.
• Patients who require medications that inhibit/induce CYP3A4 enzyme activity to control concurrent medical conditions.
• 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.
• Women 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. Women of childbearing potential will be given a pregnancy test within 7 days prior to administration of sirolimus 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.

Sponsors & Collaborators

• Denise Martin Adams: lead
• Children's Hospital Medical Center, Cincinnati: collaborator

Study Sites (2)

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Related Publications (1)

• Ricci KW, Hammill AM, Mobberley-Schuman P, Nelson SC, Blatt J, Bender JLG, McCuaig CC, Synakiewicz A, Frieden IJ, Adams DM. Efficacy of systemic sirolimus in the treatment of generalized lymphatic anomaly and Gorham-Stout disease. Pediatr Blood Cancer. 2019 May;66(5):e27614. doi: 10.1002/pbc.27614. Epub 2019 Jan 22.

  PMID: 30672136 DERIVED

Related Links

• National Organization of Vascular Anomalies
• Lymphangiomatosis \& Gorham's Disease Alliance

MeSH Terms

Conditions

Tufted angioma; Lymphangioma; Thrombocytopenia

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Denise M. Adams, M.D.
• Organization: Children's Hospital of Philadelphia

adamsdm@chop.edu

2674253010

Study Officials

• Denise M Adams, MD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Denise Adams, MD/Medical Director, Hemangioma Vascular Malformation Center, Cincinnati Children's Hospital Medical Center

Study Record Dates

• First Submitted: September 10, 2009
• First Posted: September 11, 2009
• Study Start: October 1, 2009
• Primary Completion: March 1, 2014
• Study Completion: October 1, 2020
• Last Updated: January 6, 2026
• Results First Posted: January 6, 2026

Record last verified: 2025-12

Locations

US (2)