- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00583115
Safety Study of Gleevec® in Children With Pulmonary Hypertension
September 28, 2015 updated by: Indiana University
A Phase II Study of Gleevec® (Imatinib Mesylate, NSC 716051 Formerly ST1571) in Children With Pulmonary Hypertension
The purpose of this study is to find out if the drug, Gleevec, is safe and effective in treating children with Pulmonary Hypertension.
Study Overview
Detailed Description
Idiopathic pulmonary artery hypertension (IPAH) is a rare but progressive disease in children and adults with a very high mortality from right heart failure.
Platelet derived growth factor (PDGF) has been implicated in the pulmonary artery remodeling and vascular proliferation that is a pathologic hallmark of IPAH.
Animal and clinical data support the hypothesis that activation of the PDGF receptor is critical in the development of IPAH, and inhibition of the PDGF signaling pathways may be a potential therapeutic target.
Gleevec is a tyrosine kinase inhibitor developed for treatment of certain cancers and inhibits the PDGF receptor.
Animal and preliminary clinical data suggest that Gleevec can reverse vascular remodeling and improve right heart failure.
A small clinical trial for adults with IPAH is ongoing in Europe, but there are no trials in children where the disease has a worse prognosis.
This project is a phase II, single dose pilot study to generate the hypothesis that activation of the PDGF receptor is critical in the development of IPAH, and inhibition of the PDGF signaling pathways is a potential therapeutic target.
Five patients between the ages of 8 yr to 18 yr with severe IPAH will be recruited nationally, for a 6 month trial of Imatinib.
The Specific Aim of this study is to collect preliminary data on the safety and efficacy of Gleevec in children with IPAH.
Results from this study are needed to develop a larger, multi-center trial to determine the efficacy and therapeutic impact of Gleevec in children with IPAH.
The long term goal of this work is to develop novel therapeutic strategies for treatment of IPAH in children.
This translational study of the inhibition of the PDGF receptor in children with IPAH could provide insights into the etiology of IPAH and have a major impact on the development of new treatment strategies for both children and adults with pulmonary artery hypertension from multiple origins.
Study Type
Interventional
Enrollment (Actual)
1
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Indiana
-
Indianapolis, Indiana, United States, 46202
- Indiana University School of Medicine; Riley Hospital for Children
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
8 years to 18 years (Child, Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Male and female patients between the ages of 8 -18 years of age.
- Diagnosis of idiopathic (or primary) pulmonary arterial hypertension according to the Venice Classification system (2003).54, 55
- Functional classification of WHO class III - IV.
- Pulmonary vascular resistance (PVR) >300 dynes / sec / cm5.
- IPAH medications stable for at least 3 mo prior to baseline visit.
- Female patients of child bearing potential who are sexually active must have negative pregnancy test within 7 days prior to initiation of study drug and use a double-barrier local contraception, i.e., intra-uterine device plus condom, or spermicidal gel plus condom up to the Study Completion visit.
- Able to communicate well with the investigator, to understand and comply with the requirements of the study. Able to verbalize understanding and sign the written informed assent.
- Parents, or legal guardians, must be able to communicate well with the investigator, to understand and comply with the requirements of the study. They must verbalize understanding and sign the written informed consent statement.
Exclusion Criteria:
- Pre-existing lung disease including parasitic diseases affecting lungs, bronchial asthma, congenital abnormalities of the lungs, thorax and diaphragm.
- Congenital heart disease, left ventricular failure, or left-sided obstructive lesion (pulmonary venous hypertension with pulmonary capillary wedge pressure > 12 mmHg) detected at right heart catheterization.
- Chronic thromboembolic pulmonary hypertension, congenital or acquired deficiencies of blood coagulation, deficient thrombocyte function, thrombocytopenia < 40,000/μl, or Sickle Cell anemia.
- Pregnancy, breast feeding, or lack of safe contraception (hormonal contraception, IUD, bilateral tubal ligation, hysterectomy) in premenopausal women.
- Hepatic insufficiency with transaminase levels >4-fold the upper limit of normal, or a bilirubin > 2-fold the upper limit of normal.
- Renal insufficiency (serum creatinine > 200 μmol/l).
- History of clinically significant drug allergy or history of atopic allergy (asthma, urticaria, eczematous dermatitis). A known hypersensitivity to the study drug, or drugs similar to the study drug.
- Previous therapeutic radiation of lungs or mediastinum.
- Participation in any treatment studies within 3 months prior to dosing, or longer if required by local regulations, and for any other limitation of participation based on local regulations.
- History of immunodeficiency diseases, including a positive HIV (ELISA and Western blot) test result, or a positive Hepatitis B surface antigen (HBsAg), or positive Hepatitis C test result.
Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of drugs, such as a history of inflammatory bowel syndrome, gastritis, ulcers, gastrointestinal or rectal bleeding, or a history of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection.
-
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Gleevec
Drug taken orally 260mg/M2/day once per day
|
260 mg/M2/day, given once daily by mouth
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
1) Safety and Tolerability as Determined by Laboratory Evaluation, Physical Examination, Echocardiographic Analysis, and Adverse Events, and 2) Efficacy as Determined by an Increase in the Non-encouraged 6 Minute Walk Test From Baseline.
Time Frame: 6 months
|
6 months
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
1) Decrease in Pulmonary Artery Pressures and Vascular Resistance as Determined by Cardiac Catheterization, 2) Time to Clinical Worsening,3) Survival.
Time Frame: 6 months
|
6 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: R. Mark Payne, MD, Indiana University School of Medicine
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
October 1, 2007
Primary Completion (Actual)
August 1, 2013
Study Completion (Actual)
December 1, 2013
Study Registration Dates
First Submitted
December 20, 2007
First Submitted That Met QC Criteria
December 28, 2007
First Posted (Estimate)
December 31, 2007
Study Record Updates
Last Update Posted (Estimate)
October 29, 2015
Last Update Submitted That Met QC Criteria
September 28, 2015
Last Verified
September 1, 2015
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 0702-21
- Internally funded (Indiana University)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Pulmonary Hypertension
-
Sheffield Teaching Hospitals NHS Foundation TrustUniversity of SheffieldCompletedIdiopathic Pulmonary Arterial Hypertension | Chronic Thromboembolic Pulmonary HypertensionUnited Kingdom
-
Centre Chirurgical Marie LannelongueUnknownChronic Thrombo-embolic Pulmonary Hypertension and Pulmonary Arterial HypertensionFrance
-
Heidelberg UniversityMerck Sharp & Dohme LLCRecruitingChronic Thromboembolic Pulmonary Hypertension | Primary Pulmonary Arterial HypertensionGermany
-
University of South FloridaWithdrawnPulmonary Arterial Hypertension | Familial Primary Pulmonary Hypertension | Idiopathic Pulmonary Arterial Hypertension | Primary Pulmonary HypertensionUnited States
-
BayerCompletedPrimary HypertensionChina
-
Vanderbilt University Medical CenterJohns Hopkins UniversityCompletedPulmonary Arterial Hypertension | Idiopathic Pulmonary Arterial Hypertension | Associated Pulmonary Arterial Hypertension | Heritable Pulmonary Arterial HypertensionUnited States
-
Papworth Hospital NHS Foundation TrustMerck Sharp & Dohme LLCCompleted
-
University of Kansas Medical CenterRecruitingPulmonary Arterial Hypertension | Pulmonary Hypertension | Chronic Thromboembolic Pulmonary Hypertension | Pulmonary Hypertension Due to Left Heart Disease | Pulmonary Hypertension, Primary, 4 | Pulmonary Hypertension, Primary, 2 | Pulmonary Hypertension, Primary, 3 | Pulmonary Hypertension, Primary and other conditionsUnited States
-
University of ZurichCompletedPulmonary Hypertension | Pulmonary Artery Hypertension | Chronic Thromboembolic Pulmonary HypertensionSwitzerland
-
Mads ErsbøllRecruitingPulmonary Arterial Hypertension | Chronic Thromboembolic Pulmonary HypertensionDenmark
Clinical Trials on Gleevec
-
M.D. Anderson Cancer CenterNovartis PharmaceuticalsCompletedPolycythemia Vera | Chronic Myelomonocytic Leukemia | Hypereosinophilic Syndrome | Chronic Myeloid Leukemia | MastocytosisUnited States
-
National Cancer Institute (NCI)CompletedSclerotic Graft Versus Host Disease | Imatinib MesylateUnited States
-
M.D. Anderson Cancer CenterNovartisCompletedGastrointestinal Stromal TumorsUnited States
-
M.D. Anderson Cancer CenterNovartisCompletedAcute Myelogenous Leukemia | Chronic Myelogenous Leukemia | Agnogenic Myeloid MetaplasiaUnited States
-
Jewish General HospitalNovartis PharmaceuticalsTerminatedChronic Lymphocytic LeukemiaCanada
-
M.D. Anderson Cancer CenterCompletedChronic Myelogenous LeukemiaUnited States
-
University of PittsburghNovartisCompleted
-
Annick DesjardinsAstraZeneca; Novartis PharmaceuticalsCompletedGlioblastoma | GliosarcomaUnited States
-
Steven E. CoutreNovartisTerminatedEosinophilia | Hypereosinophilic SyndromeUnited States
-
Kent RobertsonCompletedNeurofibromatosis | NeurofibromasUnited States