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

• 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. [ Time Frame: at baseline, at 24, 48 and 72 weeks ] [ Designated as safety issue: No ]
  

• 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. [ Time Frame: Every four or two weeks depending on whether patients are started on Gleevec only or on both Gleevec and Avastin ] [ Designated as safety issue: Yes ]
  

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.