Intraluminal Pulmonary Vein StenosisPhase 2NCT00215046
Vinblastine and Methotrexate in Children With Pulmonary Vein Stenosis
A Phase 2 study testing Vinblastine and Methotrexate in people with Intraluminal Pulmonary Vein Stenosis, run by Boston Children's Hospital at 2 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Intraluminal Pulmonary Vein Stenosis
- What is being tested?
- Vinblastine and Methotrexate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 2 sitesUnited States
- Study dates
- Mar 2000to Oct 2006
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Diagnosis can be based on clinical and radiographic grounds or at the time of biopsy or prior surgical procedures. The diagnosis must be consistent with multivessel pulmonary stenosis.
- There must be evidence of severe pulmonary vein stenosis in at least two pulmonary veins.
- Evidence of myofibroblast neo-proliferation, if biopsies were obtained.
- Staging must include a complete cardiovascular evaluation including echocardiogram, and EKG.
- Accepted organ function includes:
- Creatinine < 1.5 x normal for age.
Show all 11Show fewer
- SGPT, Bilirubin < 1.5 x normal for age.
- ANC ³ 1,500/mm3, Hemoglobin ³ 10g/dl, Platelets ³ 100,000/mm3
- Placement of a permanent central venous line. CVL access is necessary in all patients as vinblastine is a vesicant and will cause a tissue burn if infiltrated into the skin. Because a CVL may interfere with proper cardiac assessment in this patient population, the study physician will be made aware prior to the placement of a line.
- Patients may be listed for a lung transplant while enrolled on this study.
- All patients must have given written informed consent according to institutional guidelines.
Who cannot join
None listed.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Children's Hospital Boston
Boston, Massachusetts, 02115
Dana Farber Cancer Institute
Boston, Massachusetts, 02115
About this study
Official title: Vinblastine and Methotrexate in Children With Multivessel Pulmonary Vein Stenosis-A Phase II Study
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.
Read more
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.
Read the 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.
- Conditions
- Intraluminal Pulmonary Vein Stenosis
- Being tested
- Vinblastine, Methotrexate
- Keywords
- vinblastine, methotrexate
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VinblastineDrug
Also called antimicrotubule drug
drug - dosage and frequency is based on size of patient and response to treatment.
MethotrexateDrug
Also called Trexall
drug - dosage is based on size of patient and frequency and duration is based on response to treatment.
| Study group | Role | What they receive |
|---|---|---|
| Drug | Experimental | no randomization, all patients receive experimental drugs Receives: Drug: Vinblastine; Drug: Methotrexate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Clinical status is assessed at one year for efficacy. Additionally, the toxicity are assessed at this time for the safety endpoint.
Measured: 1 year
Secondary outcomes (1)
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.
Survival is evaluated one year after starting treatment.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2005 (estimated)
- Study startMar 2000
- Primary completionOct 2006
- Study completionOct 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Intraluminal Pulmonary Vein StenosisStudies of the same condition, open and under way.
- More trials run by Boston Children's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boston Children's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Dana-Farber Cancer Institute
- Investigators
- Mark W Kieran, MD,PhD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00215046
- Sponsor's protocol ID
- CH 02-04-054 R
- Status last verified
- Jun 2011
- First submitted
- 15 Sep 2005
- Last updated
- 27 Jun 2011
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 27 Jun 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vinblastine and Methotrexate in Children With Multivessel Pulmonary Vein Stenosis-A Phase II Study
- ClinicalTrials.gov ID
- NCT00215046
- Acronym / sponsor ID
- CH 02-04-054 R
- Conditions
- Intraluminal Pulmonary Vein Stenosis
- Keywords
- vinblastine, methotrexate
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Boston Children's HospitalUniversity, hospital or other
- Collaborators
- Dana-Farber Cancer Institute
- Study start
- Mar 2000
- Primary completion
- Oct 2006 (actual)
- Study completion
- Oct 2006 (actual)
- First posted
- 22 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Drug | Experimental | Drug: Vinblastine, Drug: Methotrexateno randomization, all patients receive experimental drugs |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (11 listed)
- Diagnosis can be based on clinical and radiographic grounds or at the time of biopsy or prior surgical procedures. The diagnosis must be consistent with multivessel pulmonary stenosis.
- There must be evidence of severe pulmonary vein stenosis in at least two pulmonary veins.
- Evidence of myofibroblast neo-proliferation, if biopsies were obtained.
- Staging must include a complete cardiovascular evaluation including echocardiogram, and EKG.
- Accepted organ function includes:
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VinblastineAlso: antimicrotubule drugdrug - dosage and frequency is based on size of patient and response to treatment. | Drug | Drug |
| MethotrexateAlso: Trexalldrug - dosage is based on size of patient and frequency and duration is based on response to treatment. | Drug | Drug |
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.
1 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2011.
Related trials for Intraluminal Pulmonary Vein Stenosis
Active, not recruiting
Predicting Pediatric Pulmonary Vein Stenosis Outcomes Using Data Acquired During a Cardiac Catheterization
Pulmonary Vein Stenosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark W Kieran, MD,PhD principal investigator
Dana-Farber Cancer Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Vinblastine and Methotrexate in people with Intraluminal Pulmonary Vein Stenosis, run by Boston Children's Hospital at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jun 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jun 2011.