Safety Study of Gleevec® in Children With Pulmonary Hypertension

NCT ID: NCT00583115

Last Updated: 2015-10-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-10-31
• Study Completion Date: 2013-12-31

Brief Summary

The purpose of this study is to find out if the drug, Gleevec, is safe and effective in treating children with Pulmonary Hypertension.

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.

Conditions

Pulmonary Hypertension

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Gleevec

Drug taken orally 260mg/M2/day once per day

Group Type: EXPERIMENTAL

Gleevec

Intervention Type: DRUG

260 mg/M2/day, given once daily by mouth

Interventions

Gleevec

260 mg/M2/day, given once daily by mouth

Intervention Type: DRUG

Other Intervention Names

Imatinib Mesylate

Eligibility Criteria

Inclusion Criteria

1. Male and female patients between the ages of 8 -18 years of age.

2. Diagnosis of idiopathic (or primary) pulmonary arterial hypertension according to the Venice Classification system (2003).54, 55

3. Functional classification of WHO class III - IV.

4. Pulmonary vascular resistance (PVR) >300 dynes / sec / cm5.

5. IPAH medications stable for at least 3 mo prior to baseline visit.

6. 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.

7. 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.

8. 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

1. Pre-existing lung disease including parasitic diseases affecting lungs, bronchial asthma, congenital abnormalities of the lungs, thorax and diaphragm.

2. 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.

3. Chronic thromboembolic pulmonary hypertension, congenital or acquired deficiencies of blood coagulation, deficient thrombocyte function, thrombocytopenia < 40,000/μl, or Sickle Cell anemia.

4. Pregnancy, breast feeding, or lack of safe contraception (hormonal contraception, IUD, bilateral tubal ligation, hysterectomy) in premenopausal women.

5. Hepatic insufficiency with transaminase levels >4-fold the upper limit of normal, or a bilirubin > 2-fold the upper limit of normal.

6. Renal insufficiency (serum creatinine > 200 μmol/l).

7. 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.

8. Previous therapeutic radiation of lungs or mediastinum.

9. 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.

10. 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.

11. 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.

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• Minimum Eligible Age: 8 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Indiana University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

R. Mark Payne, MD

Role: PRINCIPAL_INVESTIGATOR

Indiana University School of Medicine

Locations

Indiana University School of Medicine; Riley Hospital for Children

Indianapolis, Indiana, United States

Countries

United States

Other Identifiers

Internally funded

Identifier Type: OTHER

Identifier Source: secondary_id

0702-21

Identifier Type: -

Identifier Source: org_study_id