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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gregory Yanik, MD, University of Michigan Cancer Center
ClinicalTrials.gov Identifier:
NCT00141726
First received: August 30, 2005
Last updated: June 18, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Lung Injury, Acute
Respiratory Distress Syndrome, Adult
Bronchiolitis Obliterans
Drug: Etanercept
Phase 2

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

Resource links provided by NLM:


Further study details as provided by University of Michigan Cancer Center:

Primary Outcome Measures:
  • Percent of Patients With a Greater Than or Equal to 10% Improvement in FEV1, or FVC, and DLCO [ Time Frame: week 12 post therapy ] [ Designated as safety issue: Yes ]
    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) .


Secondary Outcome Measures:
  • Percentage of Participants That Experience Grade 3 to 4 Adverse Events [ Time Frame: continuously (and week 4, week 8 and week 12, week 20) ] [ Designated as safety issue: Yes ]
    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.

  • To Evaluate the Effect of Etanercept on BAL Fluid and Serum Markers of Pulmonary Inflammation. [ Time Frame: Pre-therapy (w. BAL), week 4, week 8 and week 12 (w. BAL), week 20 ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: Pre-therapy, week 12, week 20 ] [ Designated as safety issue: Yes ]

Enrollment: 34
Study Start Date: October 2003
Study Completion Date: February 2009
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: etanercept treatment
Etanercept for lung injury
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.
Other Name: Enbrel

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

Ages Eligible for Study:   6 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00141726

Locations
United States, Michigan
The University of Michigan Cancer Center
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
University of Michigan Cancer Center
Investigators
Principal Investigator: Gregory A Yanik, MD The University of Michigan Comprehensive Cancer Center
  More Information

Publications:
Responsible Party: Gregory Yanik, MD, Professor, Department of Pediatrics, University of Michigan Cancer Center, University of Michigan Cancer Center
ClinicalTrials.gov Identifier: NCT00141726     History of Changes
Other Study ID Numbers: UMCC 3-31, IRBMED 2003-0590 and HUM 46747
Study First Received: August 30, 2005
Results First Received: March 12, 2014
Last Updated: June 18, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Michigan Cancer Center:
Enbrel
Stem Cell Transplantation
Lung Injury

Additional relevant MeSH terms:
Bronchiolitis
Bronchiolitis Obliterans
Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Acute Lung Injury
Lung Injury
Wounds and Injuries
Bronchitis
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Tract Infections
Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Thoracic Injuries
TNFR-Fc fusion protein
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Gastrointestinal Agents
Immunologic Factors

ClinicalTrials.gov processed this record on July 24, 2014