Autoimmune (idiopathic) pulmonary alveolar proteinosis Respiratory Other interstitial pulmonary diseases
Conditions
Interventions
1. Untreated observation period: week 1-12
The investigator will arrange for the participant to visit the outpatient clinic immediately before, and 6 and 12 weeks after the start of the untreated obs
formerly Immunex Corporation and now Berlex, USA) administered with a LC-PLUS® jet nebuliser (PARI Respiratory Equipment, Inc.). Patients will be trained to self-administer inhalation therapy. Lyophil
Sponsors
Niigata University Medical and Dental Hospital (Japan)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Both males and females, age over 16 years and below 80 years (as of the date of registration) 2. Patients from whom informed consent has been obtained in writing 3. Patients who can be admitted to a hospital for a short period for evaluation at the start and the end of the treatment period 4. Patients with autoimmune (idiopathic) pulmonary alveolar proteinosis who satisfy either criterion A or B below and whose serum anti-GM-CSF autoantibody level is in the positive range (over 0.5 microgram/ml): A: Typical pathological findings (pool of PAS-positive protein-like material in the alveoli) detected by transbronchial lung biopsy or surgical lung biopsy (thoracoscopic lung biopsy, etc.) B: Typical findings in bronchoalveolar lavage fluid (turbid, protein-like material; decreased macrophage count) 5. Patients with resting PO2 below 75 mmHg at supine position
Exclusion criteria
Exclusion criteria: 1. White blood cell (WBC) of 12,000/microliter or more 2. Fever of 38 degrees centigrade or more 3. Grade 2 or severer oedema 4. Malignant disease of the bone marrow 5. Complication by congestive heart failure, angina pectoris, hemorrhagic tendency, primary lung carcinoma, metastatic lung carcinoma, bronchial asthma, etc., in which Leukine® therapy and its evaluation are considered as difficult 6. Treatment with other cytokines 7. Pregnant or possibly pregnant women, lactating women, and women who desire to become pregnant during the study period 8. Patients who have undergone whole-lung lavage or repeated segmental-lung lavage within 6 months before the start of the study (this criterion does not apply to patients for whom 6 months or more have elapsed after their last lavage) 9. Other patients judged to be inappropriate for the study by the attending physician (e.g., patients who are unlikely to complete treatment or are uncooperative)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Efficacy evaluation: The primary end point will be an improvement in oxygenation as assessed by a >= 10 mm Hg decrease in the room air alveolar arterial oxygen gradient (A-aDO2). The therapy will be rated as effective in cases in which there is a >= 10 mmHg improvement in this parameter during the same period. The number of effective cases will be divided by the number of evaluation-capable cases among the total number of cases in the treatment group and that satisfy the inclusion criteria to obtain the response rate. The significance of the differences between A-aDO2 at the start and end of the untreated observation period and between the start and end of the induction treatment period will be tested by the paired t-test. 2. Safety evaluation: During the therapy and follow-up visits, patients will be examined by a physician for signs of any drug-related toxicity, including the following points: 2.1. Progression of the respiratory failure, assessed every four weeks from week 4 until week 24 (6-month visit) after initiation of therapy, and then 9, 12 and 18 months 2.2. Allergic or anaphylactic reaction with the inhalation of GMCSF, assessed every four weeks from week 4 until week 24 (6-month visit) after initiation of therapy, and then 9, 12 and 18 months 2.3. Abnormalities in laboratory findings including, but not limited to, leukocytosis, increased levels of serum creatinine and liver enzymes. These will be assessed at the start of the therapy and at outpatient follow-up at 12 and 24 weeks, and 9, 12 and 18 months 2.4. Common adverse effects caused by drug administration stated in National Cancer Institute Common Toxicity Criteria (NCI-CTC), assessed every four weeks from week 4 until week 24 (6-month visit) after initiation of therapy, and then 9, 12 and 18 months | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. The period during which the A-aDO2 level is maintained above the baseline A-aDO2 + 10 mmHg will be deemed the response period for patients in whom therapy is rated as effective. AaDO2 will be assessed before treatment and at outpatient follow-up every four weeks from week 4 until week 24, and then 9, 12 and 18 months 2. High-resolution computed tomography (HRCT) images before and after treatment will be compared. HRCT will be carried out before and at the end of the treatment (24 weeks after the start of treatment). The percentage of the area showing "ground-glass opacity" (including crazy paving) in the total area of a photocopied HRCT image is semi-quantified and rated on the six-grade scale. The mean grade will be calculated for each lung specimen. 3. The serum levels of the following respiratory function indicators will be measured before and after treatment: carcinoembryonic antigen (CEA), mucin-like antigen KL-6 (KL-6), surfactant protein A (SP-A), surfactant protein D (SP-D), and lactate dehydrogenase (LDH) 4. Bronchoalveolar lavage fluid will be checked before and at the end of the treatment (24 weeks after the start of treatment) for alveolar macrophage density, total cell count, and anti-GM-CSF autoantibody level 5. Six-minute gait test will be carried out before and at the end of the treatment (24 weeks after the start of treatment). Results will be analysed with regard to distance walked and reduction in oxygen saturation | — |
Countries
Japan
Outcome results
None listed