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Pilot Study Using Avastin and Gleevec to Treat the Progression of Intraluminal Pulmonary Vein Stenosis

Information source: Children's Hospital Boston
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Pulmonary Veno Occlusive Disease

Intervention: Bevacizumab (Avastin) and Imatinib Mesylate (Gleevec) (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Kathy Jenkins

Official(s) and/or principal investigator(s):
Kathy J Jenkins, MD, MPH, Principal Investigator, Affiliation: Children's Hospital Boston, MA

Overall contact:
Kathy J Jenkins, MD, MPH, Phone: (617)355-7275, Email: Kathy.Jenkins@cardio.chboston.org


The purpose of this study is to determine whether biologic agents Avastin and Gleevec are effective in treating the progression of multivessel intraluminal pulmonary vein stenosis in children.

Clinical Details

Official title: Adjunct Targeted Biologic Inhibition in Children With Multivessel Intraluminal Pulmonary Vein Stenosis

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Response will be measured by CT angiography or by cardiac angiography if available. Other cardiac assessment techniques will be performed as necessary to confirm findings.

Secondary outcome: Physical assessment and interim history will be performed to assess for the occurrence of adverse events. Laboratory studies will be drawn and reviewed by the oncology team. Results of these laboratory tests will guide dosing of the medication.

Detailed description: Intraluminal pulmonary vein stenosis is rare but life threatening disease that affects both infants and children. It can be isolated to a single pulmonary vein, but most often occurs in multiple vessels simultaneously. It can occur as a complicating feature of complex congenital heart disease, but can also occur in isolation in infants with otherwise normal hearts. Response to conventional surgical or transcatheter-based therapies is usually short-lived. Typically within 3 to 4 weeks the obstruction recurs. Repeat surgical attempts provide only temporary relief and eventually all of these infants die without lung transplantation. While the cause of this disease is unknown the mechanism of progressive obstruction has recently been determined through biopsy and autopsy reviews to result from neo-proliferative cells identified as myofibroblasts which have cell markers VEGF and PDGF. Chemotherapeutic agents Avastin and Gleevec have shown to inhibit myo-proliferation through these markers. The overall objective of this protocol is to conduct a pilot study using the biologic agents Avastin and Gleevec to treat progression of intraluminal pulmonary vein stenosis (PVS). From this pilot group of 10 patients we will attempt to provide an enhanced characterization of the progressive primary disease process, as well as its secondary manifestations. Results will be analyzed descriptively; data gathered from this pilot study will be used to inform further study examining safety and efficacy outcomes. The study objectives will be accomplished by achievement of the following Specific Aims: 1. To describe the feasibility of administration of Gleevec® with or without Avastin® to treat the progression of intraluminal PVS in patients with multivessel disease. Patients with PVS in conjunction with congenital heart disease (CHD) will receive Gleevec® alone, with Avastin® added if significant progression occurs; patients with primary PVS and PVS in conjunction with lung disease will be treated with both drugs simultaneously. 2. To characterize the time to progression and the proportion of patients who survive 48 weeks after enrollment. 3. To describe the toxicity associated with administration of Gleevec® with or without Avastin® during a 48 week course of treatment among patients with multivessel PVS. Response to therapy will be described by summarizing severity of obstruction, lobar involvement, lung involvement, left atrial wall involvement and mediastinal involvement and will be measured by CT angiography at baseline,24,48 and 72 weeks or by cardiac angiography if available. Other cardiac assessment techniques will be performed as necessary to confirm findings. Patients will be assessed by the oncology team regularly. At this time Lab studies will be drawn and reviewed & a physical assessment and interim history will be performed to assess for the occurrence of adverse events.


Minimum age: N/A. Maximum age: N/A. Gender(s): Both.


Eligibility Criteria: (Both groups)

- Evidence of intraluminal pulmonary vein stenosis in > 1 vessel

- Evidence of myofibroblast neo-proliferation, if biopsies were obtained

- Acceptable organ function includes:

Creatinine < 1. 5 x normal for age. Bilirubin < 1. 5 x normal for age. ALT < or = 5x normal ANC > or = 1,500/mm3, Hemoglobin > or = 10g/dl, Platelets > or = 100,000/mm3. Group A Eligibility Criteria: (begin treatment with Gleevec® only)

- Significant concomitant congenital heart defect

- Disease severity for each vessel Category 5 or lower or Category 6 or 7 in no more

than 1 vessel Group B Eligibility Criteria: (begin treatment with Gleevec® and Avastin®)

- Primary PVS (i. e. without concomitant congenital heart defect or lung disease)

- Significant concomitant lung disease

- Patients with PVS and underlying CHD who have category 6 or 7 disease in at least 2

of their pulmonary veins even after surgical or cath-based interventions.

- Accepted organ function includes:

Urine protein < 1

Locations and Contacts

Kathy J Jenkins, MD, MPH, Phone: (617)355-7275, Email: Kathy.Jenkins@cardio.chboston.org

Children's Hospital Boston, Boston, Massachusetts 02115, United States; Recruiting
Kathy J Jenkins, MD, MPH, Phone: 617-355-7275, Email: Kathy.Jenkins@cardio.chboston.org
Mark W Kieran, MD, PhD, Phone: (617) 632-4907, Email: Mark_Kieran@dfci.harvard.edu
James Lock, MD, Sub-Investigator
Laureen Sena, MD, Sub-Investigator
Kimberlee Gauvreau, ScD, Sub-Investigator
Steven Colan, MD, Sub-Investigator
Antonio Perez-Atayde, MD, Sub-Investigator
Thomas Kulik, MD, Sub-Investigator
Frederick Grant, MD, Sub-Investigator
Ted Treves, MD, Sub-Investigator
Kathy J Jenkins, MD, MPH, Principal Investigator
Mark W Kieran, MD, PhD, Sub-Investigator
Additional Information

Related publications:

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Riedlinger WF, Juraszek AL, Jenkins KJ, Nugent AW, Balasubramanian S, Calicchio ML, Kieran MW, Collins T. Pulmonary vein stenosis: expression of receptor tyrosine kinases by lesional cells. Cardiovasc Pathol. 2006 Mar-Apr;15(2):91-9.

Sadr IM, Tan PE, Kieran MW, Jenkins KJ. Mechanism of pulmonary vein stenosis in infants with normally connected veins. Am J Cardiol. 2000 Sep 1;86(5):577-9, A10.

Starting date: October 2008
Last updated: August 10, 2012

Page last updated: August 23, 2015

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