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

Condition(s) targeted: Lung Injury, Acute; Respiratory Distress Syndrome, Adult; Bronchiolitis Obliterans

Intervention: Etanercept (Drug)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: University of Michigan Cancer Center

Official(s) and/or principal investigator(s):
Gregory A Yanik, MD, Principal Investigator, Affiliation: The University of Michigan Comprehensive Cancer Center

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.

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 design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Primary outcome: To evaluate the response to etanercept therapy, based upon pulmonary function parameters (FEV1.0, FEV1.0/FVC, DLCO) in patients with sub-acute lung injury > 100 days post transplant

Secondary outcome:

To evaluate the toxicity of etanercept therapy in patients with sub-acute lung injury > 100 days post transplant.

To evaluate the effect of etanercept on BAL fluid and serum markers of pulmonary inflammation.

To examine health related quality of life parameters, including longitudinal changes in and magnitude of persistent disability in patients with sub-acute lung injury post transplant.

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.

Minimum age: 6 Years. Maximum age: N/A. Gender(s): Both.

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.

The University of Michigan Cancer Center, Ann Arbor, Michigan 48109, United States

Starting date: October 2003
Ending date: December 2009
Last updated: June 4, 2008