Study of Enbrel (Etanercept) for the Treatment Sub-Acute Pulmonary Dysfunction After Allogeneic Stem Cell Transplant

Study Overview
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Brief Summary
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The purpose of this study is to determine the effectiveness of etanercept in the treatment of patients with sub-acute lung injury following a bone marrow transplant. This study will also examine the toxicity of treatment with etanercept as well as whether there is an improved quality of life in these patients.

Detailed Description
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Lung or breathing problems can develop several months to years following a bone marrow transplant. In some cases, these breathing problems develop without any signs of germs or infection in the lungs. The name for this type of breathing problem is called Sub-Acute Lung Injury. Sub-acute lung injury often develops many months, even years following a bone marrow transplant. It is often characterized by shortness of breath, cough, wheezing and fatigue. Sub-acute lung injury can either lead to the formation of scar tissue in the lungs (making it difficult to take deep breaths), or it can cause the lungs to get weak (making people feel out of breath easily). Approximately 25 - 50% of patients with sub-acute lung injury may eventually die from the damage in their lungs. Typically, such patients die from infections that develop inside the damaged lungs. In this study, treatment with an experimental drug called Etanercept will be used. (Enbrel). The physicians feel there is the possibility that Etanercept may help improve breathing. Breathing ability will be assessed prior to treatment as well as during and after treatment so that comparisons can be made.

Official Title
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Soluble Tumor Necrosis Factor Receptor: Enbrel (Etanercept) for the Treatment of Sub-Acute Pulmonary Dysfunction Following Allogeneic Stem Cell Transplantation. A Phase II Study

Conditions
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Lung Injury, Acute, Respiratory Distress Syndrome, Adult, Bronchiolitis Obliterans

Intervention / Treatment
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* Drug: Etanercept


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Recipients of allogeneic bone marrow, cord blood, or peripheral blood stem cell transplants are eligible Age >6 years and able to complete pulmonary function testing Patients with evidence of sub-acute, non-infectious pulmonary dysfunction (OLD or RLD) Recipients of sub-ablative transplant regimens are eligible Recipients of donor leukocyte infusions (DLI) post-transplant are eligible Patients must be > 100 days post transplant Exclusion Criteria: Patients with hypotension requiring inotropic agents other than dopamine < 5mcg/ kg/ minute for blood pressure support. Patients with a positive quantitative bacterial culture from the BAL fluid (≥ 104 CFU/ ml is considered positive) Patients whose BAL fluid is positive for significant bacterial pathogens or pathogenic nonbacterial microorganisms (as defined by protocol) by special stain, culture or PCR analysis Patients who are enrolled on a phase I or phase II trial for the prophylaxis or treatment of GVHD (acute or chronic) within 7 days of study entry. Patients with known hypersensitivity to etanercept. Patients who are pregnant. Patients with CMV seropositivity at the time of study entry. Testing may include wither CMV PCR analysis or CMV pp65 testing. Evidence for multi-system organ failure.

Ages Eligible for Study
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Minimum Age: 6 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: etanercept treatment<br>Etanercept for lung injury | Drug: Etanercept<br>* Etanercept will be given on an open label, single arm basis to patients with non-infectious, sub-acute lung injury. 0.4 mg/kg/dose to a maximum of 25 mg, subcutaneously, twice weekly, for a total of 24 dosages.<br>* Other names: Enbrel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Patients With a Greater Than or Equal to 10% Improvement in FEV1, or FVC, and DLCO | Response was defined as a greater than or equal to 10% improvement in the absolute value for FEV1 (for obstructive defects) or FVC (for restrictive defects), and DLCO (Diffusing Capacity of the Lungs for Carbon Monoxide) . | week 12 post therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants That Experience Grade 3 to 4 Adverse Events | To evaluate the toxicity of etanercept therapy in patients with sub-acute lung injury > 100 days post transplant, the percent incidence of grade 3 to 4 adverse events among evaluable patients was calculated. | continuously (and week 4, week 8 and week 12, week 20) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Enbrel, Stem Cell Transplantation, Lung Injury