Ignite Creation Date:
2024-05-05 @ 12:01 PM
Last Modification Date:
2024-10-26 @ 9:18 AM
Study NCT ID:
NCT00215046
Status:
COMPLETED
Last Update Posted:
2011-06-27
First Post:
2005-09-15
Brief Title:
Vinblastine and Methotrexate in Children With Pulmonary Vein Stenosis
Sponsor:
Boston Childrens Hospital
Organization:
Boston Childrens Hospital
Study Overview
Official Title:
Vinblastine and Methotrexate in Children With Multivessel Pulmonary Vein Stenosis-A Phase II Study
Status:
COMPLETED
Status Verified Date:
2011-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
12 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
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
12 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 Description:
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 cyclophosphamide-based regimens this combination has the distinct advantages of few acute side effects and no known long-term toxicities such as infertility or second malignancy These agents have been used for over 30 years to treat infant and childhood malignancies Over the last five years methotrexate and vinblastine have been used to treat 9 children with recurrent desmoid tumor a lesion similar although not identical to the abnormality present in patients with pulmonary vein stenosis This regimen had minimal acute toxicity limited to mild to moderate nausea which is easily controlled with anti-emetic therapy minimal alopecia mild hepatic inflammation and mild myelosuppression An addition advantage is that these drugs do not interfere with listing for lung transplantation an important factor in the overall treatment options for this patient population Instead of high-dose administration of chemotherapy that catches only those cells in cycle at the time of administration the low-dose chronic weekly administration continues to catch proliferating cells as they continually come into cycle This may explain why the only other trial of chemotherapy with high-dose cytoxan was unsuccessful Of the 9 children with desmoid lesions who received vinblastine and methotrexate therapy four patients were treated for 18 months or longer At the time of the last report no patient had progressive disease during therapy Two children had radiographically stable disease 1 and 2 years after treatment Two children had stable disease for 1 and 2 years after treatment and then had disease progression Thus this drug combination is well-tolerated has minimal side effects and has demonstrated clinical activity against a closely related type of lesion
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 cyclophosphamide-based regimens this combination has the distinct advantages of few acute side effects and no known long-term toxicities such as infertility or second malignancy These agents have been used for over 30 years to treat infant and childhood malignancies Over the last five years methotrexate and vinblastine have been used to treat 9 children with recurrent desmoid tumor a lesion similar although not identical to the abnormality present in patients with pulmonary vein stenosis This regimen had minimal acute toxicity limited to mild to moderate nausea which is easily controlled with anti-emetic therapy minimal alopecia mild hepatic inflammation and mild myelosuppression An addition advantage is that these drugs do not interfere with listing for lung transplantation an important factor in the overall treatment options for this patient population Instead of high-dose administration of chemotherapy that catches only those cells in cycle at the time of administration the low-dose chronic weekly administration continues to catch proliferating cells as they continually come into cycle This may explain why the only other trial of chemotherapy with high-dose cytoxan was unsuccessful Of the 9 children with desmoid lesions who received vinblastine and methotrexate therapy four patients were treated for 18 months or longer At the time of the last report no patient had progressive disease during therapy Two children had radiographically stable disease 1 and 2 years after treatment Two children had stable disease for 1 and 2 years after treatment and then had disease progression Thus this drug combination is well-tolerated has minimal side effects and has demonstrated clinical activity against a closely related type of lesion
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None