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

Respiratory Distress Syndrome, Adult Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00141726
• Other study ID #: UMCC 3-31
• Secondary ID: IRBMED 2003-0590
• Status: Completed
• Phase: Phase 2
• First received: August 30, 2005
• Last updated: November 4, 2015
• Start date: October 2003
• Est. completion date: February 2009

Study information

• Verified date: November 2015
• Source: University of Michigan Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: February 2009
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Lung Injury
• Bronchiolitis
• Bronchiolitis Obliterans
• Lung Injury
• Lung Injury, Acute
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn

Intervention

Drug:
• Etanercept
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.

Locations

Country	Name	City	State
United States	The University of Michigan Cancer Center	Ann Arbor	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
University of Michigan Cancer Center

Country where clinical trial is conducted

United States, 

References & Publications (1)

Yanik GA, Mineishi S, Levine JE, Kitko CL, White ES, Vander Lugt MT, Harris AC, Braun T, Cooke KR. Soluble tumor necrosis factor receptor: enbrel (etanercept) for subacute pulmonary dysfunction following allogeneic stem cell transplantation. Biol Blood Ma — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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)	Yes