Study of Subcutaneous Injection of Low-dose rhGM-CSF +/- WLL in PAP.

Study Overview
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Brief Summary
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The purpose of this study is to establish an efficient and economic treatment scheme by evaluation of the safety and efficacy of subcutaneous injection of low-dose rhGM-CSF, or of similar injection after whole lung lavage , in patients with PAP.

Detailed Description
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The purpose of this study is to establish an efficient and economic treatment scheme by evaluation of the safety and efficacy of subcutaneous injection of low-dose rhGM-CSF, or of similar injection after whole lung lavage , in patients with PAP. During the observation, study visits will occur at the end of each month. During the 1-year follow-up period which is lasting 6 months after the treatment, all participants will be required to check the various efficacy indicators.

Official Title
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Study of Subcutaneous Injection of Low-dose Recombinant Granulocyte Macrophage-Colony Stimulating Factor (rhGM-CSF) +/- Whole Lung Lavage(WLL) in Pulmonary Alveolar Proteinosis.

Conditions
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Pulmonary Alveolar Proteinosis

Intervention / Treatment
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* Drug: rhGM-CSF
* Procedure: Whole Lung Lavage(WLL)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed PAP patients Aged 17-80 Signed informed consent Exclusion Criteria: Secondary PAP Received whole lung lavage therapy within 4 weeks before enrollment Received previous GM-CSF therapy within 6 months before enrollment WBC≥12,000/ul fever≥38℃ Severe edema, severe liver, kidney, lung and cardiovascular disease. Pregnant，planning to get pregnant or nursing Inability to express the subjective discomfort Serious drug allergy history, E.coli preparation or rhGM-CSF serious allergy history

Ages Eligible for Study
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Minimum Age: 17 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: D1<br>Patients diagnosed with PAP will be received rhGM-CSF 1.25 ug/kg/d subcutaneously for 1 month, before evaluation on the 30th day (±3 day). If the treatment is effective, participants may be entered into low-dose group(D1)(rhGM-CSF administration 1.25 ug/kg/d, qd, sc, for 2 months，then rhGM-CSF administration 1.25 ug/kg/d, qod, sc, for 3 months), when the chest CT absorption≥25% , and /or the PaO2 elevated by 5 mm Hg. | Drug: rhGM-CSF<br>* GM-CSF will be given subcutaneously according to the rule in different groups.<br>* Other names: Granulocyte Macrophage-Colony Stimulating Factor;|
| Experimental: D2<br>Patients diagnosed with PAP will be received rhGM-CSF 1.25 ug/kg/d subcutaneously for 1 month, before evaluation on the 30th day (±3 day). When the treatment is ineffective, and anti-GM-CSF antibody titers level ≥1:1000，the dose will be increased to 2.5 ug/kg/d. After 2 months, if the clinical response was optimal, that dose is continued for 3 months, and defined as group 2(D2). | Drug: rhGM-CSF<br>* GM-CSF will be given subcutaneously according to the rule in different groups.<br>* Other names: Granulocyte Macrophage-Colony Stimulating Factor;|
| Experimental: D3<br>Patients diagnosed with PAP will be received rhGM-CSF 1.25 ug/kg/d subcutaneously for 1 month, before evaluation on the 30th day (±3 day). When the treatment is ineffective, and anti-GM-CSF antibody titers level ≥1:1000，the dose will be increased to 2.5 ug/kg/d. After 2 months, if the clinical response was not optimal, the patients will receive whole lung lavage(WLL), who are defined as group 3(D3). | Drug: rhGM-CSF<br>* GM-CSF will be given subcutaneously according to the rule in different groups.<br>* Other names: Granulocyte Macrophage-Colony Stimulating Factor;|
| Active Comparator: D4<br>Patients diagnosed with PAP will be received rhGM-CSF 1.25 ug/kg/d subcutaneously for 1 month, before evaluation on the 30th day (±3 day). When the treatment is ineffective, and anti-GM-CSF antibody titers level <1:1000，the patients will receive whole lung lavage(WLL), then give rhGM-CSF administration (1.25 ug/kg/d) for 3 months, which belong to group4(D4). | Drug: rhGM-CSF<br>* GM-CSF will be given subcutaneously according to the rule in different groups.<br>* Other names: Granulocyte Macrophage-Colony Stimulating Factor;Procedure: Whole Lung Lavage(WLL)<br>* using double lumen endotracheal tube (DLT) to selectively lavage one lung<br>* Other names: WLL;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvements in double pulmonary diffuse lesions （Chest CT score ） |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical symptoms observation: shod of breath, cough (according to each score standard） |  | 6 months | 
| Granulocyte Macrophage Colony Stimulating Factor(GM-CSF) Antibody titer change |  | 6 months | 
| Improvements in pulmonary function | Pulmonary function tests include residual volume/total lung capacity(RV/TLC), forced vital capacity(FVC), forced expiratory volume in one second/forced vital capacity(FEV1/FVC), diffusing capacity of carbon monoxide(DLCO). | 6 months | 
| Improvements in arterial blood gas, including alveolar-arterial oxygen difference(A-aDO2), partial pressure of oxygen(PaO2), partial pressure of carbon dioxide in artery(PaCO2), arterial oxygen saturation(SaO2). |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulmonary, Pulmonary Alveolar Proteinosis, PAP