Overview

This trial is active, not recruiting.

Condition pulmonary veno occlusive disease
Treatment bevacizumab (avastin) and imatinib mesylate (gleevec)
Phase phase 2
Sponsor Kathy Jenkins
Start date October 2008
End date December 2015
Trial size 20 participants
Trial identifier NCT00891527, 07060249

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
bevacizumab (avastin) and imatinib mesylate (gleevec) Bevacizumab (rhuMAb VEGF, Avastin), NSC 704865
Imatinib Mesylate Orange to grayish orange, opaque, 100mg capsules dissolved in 50-100mls of mineral water or apple juice. Given at 340mg/m2 once daily, preferably with a meal. Bevacizumab Clear to slightly opalescent liquid. Given at 10mg/kg once every 2 weeks IV. The calculated dose should be placed in an IV bag and diluted with 0.9% sodium chloride to obtain a final volume of 25-100mls. The vials contain no antibacterial preservatives. Once diluted, must be administered within 8 hrs. Initially administered over 90 mins. If no adverse reactions occur, 2nd dose administered over 60 mins. If still no adverse reactions, subsequent doses administered over 30 mins. If infusion-related adverse reactions occur, further infusions administered over the shortest period that was well tolerated.

Primary Outcomes

Measure
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

Secondary Outcomes

Measure
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

Eligibility Criteria

Male or female participants of any age.

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

Additional Information

Official title Adjunct Targeted Biologic Inhibition in Children With Multivessel Intraluminal Pulmonary Vein Stenosis
Principal investigator Kathy J Jenkins, MD, MPH
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.
Trial information was received from ClinicalTrials.gov and was last updated in February 2016.
Information provided to ClinicalTrials.gov by Children's Hospital Boston.