Clinical Trial: Vinblastine and Methotrexate in Children With Pulmonary Vein Stenosis

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Vinblastine and Methotrexate in Children With Multivessel Pulmonary Vein Stenosis-A Phase II Study

Brief Summary:

To evaluate the efficacy of the chemotherapeutic agents vinblastine and methotrexate in the treatment of two groups of children with multivessel pulmonary vein stenosis. Group 1 will contain children with multivessel pulmonary vein stenosis who do not have structural heart disease, and Group 2 will consist of children with multivessel pulmonary vein stenosis and concomitant structural heart disease.

The primary outcome variable for efficacy is patient status one year after the start of treatment, where status is classified as either failure or success. Failure is defined as death or evidence of progressive obstruction at any time over the course of treatment as defined in the protocol. Success constitutes complete or partial response to treatment or stability of disease. Secondary outcome variables for efficacy are survival, time from diagnosis of pulmonary vein stenosis until failure, and change in patient classification on a scale measuring the severity of the obstructive disease.

1.2 To assess the safety of vinblastine and methotrexate in the treatment of multivessel pulmonary vein stenosis.

The primary outcome variable for safety is any occurrence of toxicity related to the administration of the chemotherapeutic agents over the treatment period.


Detailed Summary:

We sought to develop a regimen that might successfully suppress myofibroblastic proliferation in infants and children with progressive pulmonary vein stenosis. A number of factors need to be considered when proposing novel treatment options for patients with multivessel pulmonary vein stenosis. Specifically:

  • Treatment should be directed against a specific target, in this case excessive proliferation of myofibroblasts.
  • Treatment should have known activity against the target cell.
  • Treatment should be well-tolerated in the patient group. In this case, agents with minimal hemodynamic side effects would be preferred.
  • Treatment should not preclude patients from participation in other potentially effective therapies. Specifically, agents that do not cause significant myelosuppression would allow listing for transplantation.
  • Treatment should not interfere with normal growth and development, and should have minimal if any risk for long-term toxicity or second tumors.

After considering these factors, we chose to administer two chemotherapeutic agents, vinblastine and methotrexate. Vinblastine and methotrexate have over 30 years of usage and are well-tolerated. The agents used are given in low-dose and do not usually cause nausea or vomiting, nor do they cause significant immunosuppression which, if present, could lead to a risk of infection and fever.

Desmoid tumors, also referred to as infantile fibromatosis, overlap with infantile myofibromatosis. A combination of standard agents that has been successfully used to treat desmoid tumors in infants is vinblastine and methotrexate (24). As opposed to cyclophos
Sponsor: Boston Children’s Hospital

Current Primary Outcome: The primary outcome variable for efficacy is patient status one year after the start of treatment, where status is classified as either failure or success. Failure is defined as death or evidence of progressive obstruction at any time over the course of [ Time Frame: 1 year ]

Clinical status is assessed at one year for efficacy. Additionally, the toxicity are assessed at this time for the safety endpoint.


Original Primary Outcome: The primary outcome variable for efficacy is patient status one year after the start of treatment, where status is classified as either failure or success. Failure is defined as death or evidence of progressive obstruction at any time over the course of

Current Secondary Outcome: Secondary outcome variables for efficacy are survival, time from diagnosis of pulmonary vein stenosis until failure, and change in patient classification on a scale measuring the severity of the obstructive disease. [ Time Frame: 1 year ]

Survival is evaluated one year after starting treatment.


Original Secondary Outcome: Secondary outcome variables for efficacy are survival, time from diagnosis of pulmonary vein stenosis until failure, and change in patient classification on a scale measuring the severity of the obstructive disease.

Information By: Boston Children’s Hospital

Dates:
Date Received: September 15, 2005
Date Started: March 2000
Date Completion:
Last Updated: June 22, 2011
Last Verified: June 2011