Bronchiolitis Obliterans, Lung Injury, Acute, Respiratory Distress Syndrome, Adult
Conditions
Keywords
Enbrel, Stem Cell Transplantation, Lung Injury
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.
Interventions
DRUGEtanercept
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.
Sponsors
University of Michigan Rogel Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Patients With a Greater Than or Equal to 10% Improvement in FEV1, or FVC, and DLCO | week 12 post therapy | 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
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants That Experience Grade 3 to 4 Adverse Events | continuously (and week 4, week 8 and week 12, week 20) | 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. |
Countries
United States
Participant flow
Recruitment details
Study subjects were recruited from the Blood and Marrow Stem Cell Program at the University of Michigan Medical Center between 2001 and 2008, all subjects having received an allogeneic Stem Cell Transplant (SCT) at least 100 days before study entry.
Participants by arm
| Arm | Count |
|---|---|
| Etanercept Treatment Etanercept for lung injury
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. | 34 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Completed <50% Scheduled Dosing | 3 |
Baseline characteristics
| Characteristic | Etanercept Treatment |
|---|---|
| Age, Continuous | 39 years |
| Cell Source Marrow | 9 participants |
| Cell Source Pluripotent Stem Cell (PSC) | 25 participants |
| Chronic Graft Versus Host Disease (GVHD) Present No | 0 participants |
| Chronic Graft Versus Host Disease (GVHD) Present Yes | 34 participants |
| Diagnosis Acute Lymphoblastic Leukemia (ALL) | 3 participants |
| Diagnosis AML/MDS/MF | 16 participants |
| Diagnosis Chronic Mylogenous Leukemia (CML) | 5 participants |
| Diagnosis Myeloma | 2 participants |
| Diagnosis NHL/CLL | 6 participants |
| Diagnosis Nonmalignant | 2 participants |
| Donor Type Matched Related Donor (MRD) | 22 participants |
| Donor Type Unrelated Donor (URD) | 12 participants |
| Human Leukocyte Antigen (HLA) Match HLA Matched | 31 participants |
| Human Leukocyte Antigen (HLA) Match Mismatch | 3 participants |
| Lung Injury Pattern Obstructive | 25 participants |
| Lung Injury Pattern Restrictive | 9 participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 21 / 34 |
| serious Total, serious adverse events | 5 / 34 |
Outcome results
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) .
Time frame: week 12 post therapy
Population: 34 subjects were enrolled. Thirty-one of 34 subjects were evaluable for response, with three subjects completing \<50% of scheduled dosing.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Etanercept Treatment | Percent of Patients With a Greater Than or Equal to 10% Improvement in FEV1, or FVC, and DLCO | ≥10% Improvement in FEV1 / FVC | 32 percent evaluable participants |
| Etanercept Treatment | Percent of Patients With a Greater Than or Equal to 10% Improvement in FEV1, or FVC, and DLCO | ≥10% Improvement in DLCO | 16 percent evaluable participants |
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.
Time frame: continuously (and week 4, week 8 and week 12, week 20)
Population: 34 subjects were enrolled and evaluated for adverse events.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Etanercept Treatment | Percentage of Participants That Experience Grade 3 to 4 Adverse Events | Incidence of Grad 3 to 4 Infection | 14 percentage of participants |
| Etanercept Treatment | Percentage of Participants That Experience Grade 3 to 4 Adverse Events | Incidence of Grade 3 to 4 Electrolyte Toxicities | 11 percentage of participants |
| Etanercept Treatment | Percentage of Participants That Experience Grade 3 to 4 Adverse Events | Incidence of Grade 3 to 4 Hyperglycemia | 8 percentage of participants |
| Etanercept Treatment | Percentage of Participants That Experience Grade 3 to 4 Adverse Events | Incidence of Grade 3 to 4 Renal/GU Toxicities | 6 percentage of participants |
| Etanercept Treatment | Percentage of Participants That Experience Grade 3 to 4 Adverse Events | Incidence of Grade 3 to 4 Hepatic Toxicities | 6 percentage of participants |
| Etanercept Treatment | Percentage of Participants That Experience Grade 3 to 4 Adverse Events | Incidence of Grade 3 to 4 Pain | 6 percentage of participants |
| Etanercept Treatment | Percentage of Participants That Experience Grade 3 to 4 Adverse Events | Incidence of Grade 3 to 4 Hypertension | 3 percentage of participants |
| Etanercept Treatment | Percentage of Participants That Experience Grade 3 to 4 Adverse Events | Incidence of Grade 3 to 4 GI Toxicities | 3 percentage of participants |
| Etanercept Treatment | Percentage of Participants That Experience Grade 3 to 4 Adverse Events | Incidence of Grade 3 to 4 CNS Toxicities | 3 percentage of participants |
| Etanercept Treatment | Percentage of Participants That Experience Grade 3 to 4 Adverse Events | Incidence of Grade 3 to 4 Thrombocytopenia | 3 percentage of participants |