Study of Subcutaneous Injection of Low-dose Recombinant Granulocyte Macrophage-Colony Stimulating Factor (rhGM-CSF) +/- Whole Lung Lavage(WLL) in Pulmonary Alveolar Proteinosis.
Overview
- Phase
- Phase 2
- Intervention
- rhGM-CSF
- Conditions
- Pulmonary Alveolar Proteinosis
- Sponsor
- Shanghai Pulmonary Hospital, Shanghai, China
- Enrollment
- 40
- Locations
- 1
- Primary Endpoint
- Improvements in double pulmonary diffuse lesions （Chest CT score ）
- Last Updated
- 12 years ago
Overview
Brief Summary
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
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.
Investigators
Huiping Li
Professor,Chief of Dept. of Respiratory Medicine
Shanghai Pulmonary Hospital, Shanghai, China
Eligibility Criteria
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
Arms & Interventions
D1
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.
Intervention: rhGM-CSF
D2
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).
Intervention: rhGM-CSF
D3
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).
Intervention: rhGM-CSF
D4
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).
Intervention: rhGM-CSF
D4
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).
Intervention: Whole Lung Lavage(WLL)
Outcomes
Primary Outcomes
Improvements in double pulmonary diffuse lesions （Chest CT score ）
Time Frame: 6 months
Secondary Outcomes
- 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(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)