Idiopathic pulmonary alveolar proteinosis
Conditions
Interventions
Intervention type:DRUG
Name of intervention:Granulocyte-macrophage colony stimulating factor (GM-CSF)
Dose form / Japanese Medical Device Nomenclature:INJECTION
Route of administration / Site of appli
Sponsors
Koh Nakata, M.D., Ph.D.
Bioscience Medical Research Center (BMRC), Niigata University Medical & Dental Hospital
Toshihiro NUKIWA, M.D., Ph.D., Department of Respiratory Medicine, Tohoku University Medical School
Yoshikazu INOUE, M.D., Ph.D., National Hospital Organization Kinki-Chuo Chest Medical Center
Toshinori TAKADA M.D., Ph.D., Department of Internal Medicine, Niigata University Medical and Dental Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patients aged 16 - 80 (on the day of enrollment). Patients aged 16 - 19 must provide a signed consent from parents/guardians. 2. A written consent from the patient or his/her parents/guardians. 3. Able to be hospitalized for a short time. 4. Idiopathic pulmonary alveolar proteinosis with serum anti-GM-CSF autoantibody titer grater than 3 mcg/ml and meets A or B below: A. typical pathological findings (accumulation of PAS-positive proteinaceous materials within the alveoli) on transbronchial lung biopsy or surgical lung biopsy (incl. thoracoscopy lung biopsy) B. bronchoalveolar lavage (BAL) fluid showing features characteristic of iPAP (i.e., opaque appearance, proteinaceous materials, low alveolar macrophage count). 5. Resting Pao2 < 75 mmHg on room air. 6. Diagnosis of PAP 7. Life expectancy longer than 3 months. 8. Confirmed presence of anti-GM-CSF autoantibodies.
Exclusion criteria
Exclusion criteria: 1. WBC count >/= 12000/mm3 2. Concomitant bronchial asthma. 3. Fever of >/= 38 degrees Celsius. 4. Edema of Grade 2 or more (CTCAE) 5. Myeloid malignancy. 6. Concomitant congestive heart failure (NYHA III - IV), angina, bleeding tendency, primary lung cancer, or metastatic lung cancer that will make assessment of treatment difficult. 7. Concurrent treatment with other cytokines. 8. Pregnant or possibly pregnant women or nursing mothers, and women planning to become pregnant during the study. 9. Whole lung lavage or sequential segmental lung lavage within 6 months prior to the start of treatment. 10. Upper lung lobe fibrosis with a honeycomb pattern or emphysema on x-ray or high-resolution computed tomography (HRCT) scan of the chest performed within 6 months prior to study enrollment. 11. For any reason, is judged by the investigator/co-investigators to be inappropriate for study, including inability to complete the protocol or cooperate with the investigator/co-investigators. 12. History of serious drug allergy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Improvement in A-aDo2 at Week 24 compared with baseline | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Duration of response (defined as maintenance of >/= 10 mmHg increase from baseline in A-aDo2) 2. Changes from baseline in HRCT findings. 3. Changes from baseline in %VC and %DLco 4. Changes from baseline in serum markers (CEA, KL-6, SP-A, SP-D, LDH) | — |
Countries
Japan
Contacts
Public ContactSeiichi MARUYAMA, Ryushi TAZAWA
Bioscience Medical Research Center (BMRC), Niigata University Medical & Dental Hospital
Outcome results
None listed