Clinical trial NCT00141726: Study of Enbrel (Etanercept) for the Treatment Sub-Acute Pulmonary Dysfunction After Allogeneic Stem Cell Transplant
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Injury, Acute
Respiratory Distress Syndrome, Adult
Bronchiolitis Obliterans
Keywords: Enbrel
Stem Cell Transplantation
Lung Injury
Lead sponsor: University of Michigan Rogel Cancer Center
Sponsor class: OTHER
First posted: 2005-09-01
Enrollment: 34
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percent of Patients With a Greater Than or Equal to 10% Improvement in FEV1, or FVC, and DLCO
timeFrame: week 12 post therapy
Secondary outcomes:
measure: Percentage of Participants That Experience Grade 3 to 4 Adverse Events
timeFrame: continuously (and week 4, week 8 and week 12, week 20)
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: The University of Michigan Cancer Center
state: Michigan
Study officials:
affiliation: The University of Michigan Comprehensive Cancer Center
name: Gregory A Yanik, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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 Marrow Transplant. 2012 Jul;18(7):1044-54. doi: 10.1016/j.bbmt.2011.11.031. Epub 2011 Dec 10.