This is a study to determine the efficacy and safety of granulocyte-macrophage colony-stimulating factor (GM-CSF, sargramostim) administered subcutaneously to patients with pulmonary alveolar proteinosis (PAP).

Condition	Treatment or Intervention	Phase
Pulmonary Alveolar Proteinosis	Drug: GM-CSF (granulocyte-macrophage colony-stimulating factor, sargramostim)	Phase II

PAP is a rare lung disease characterized by accumulation of surfactant phospholipids and proteins within the lungs. There is no specific pharmacologic therapy for PAP and the current practice of lung lavage under general anesthesia is invasive and has limitations. Although it is unknown if the anti GM-CSF antibody is related to the disease pathogenesis, observations suggest a role for GM-CSF in lung homeostasis as well as in the pathogenesis of PAP.

Patients will receive subcutaneous GM-CSF or placebo once a day and will be followed on an outpatient basis at 2 weeks, and 1, 2, 3, 4, 5 and 6 months after initiation of therapy. Clinical response will determine dosing schedule and will be evaluated by symptom scores, gas exchange data, and chest radiographs.

Ages Eligible for Study:  18 Years   -   70 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion criteria:

• Diagnosis of primary or idiopathic PAP
• Creatinine no greater than 2 mg/dL
• Bilirubin no greater than 2 mg/dL
• Liver enzymes no greater than 3 times normal
• Women must use an effective method of contraception, be post menopausal, or be surgically sterilized

Exclusion criteria:

• Active respiratory infection
• Active cardiovascular disease (e.g., cardiogenic pulmonary edema)
• Underlying myeloproliferative disorder or leukemia
• Other secondary cause of PAP (e.g., occupational exposure to silica or HIV with PCP)
• At increased risk of side effects from GM-CSF therapy (i.e., rheumatoid arthritis, immune thrombocytopenia, or autoimmune thyroiditis)
• Previous therapy with GM-CSF
• Pregnant or nursing
• Significant renal or liver disease

Mani S. Kavuru, M.D.      216-445-6972    kavurum@ccf.org

Colorado
      National Jewish Medical Center, Denver,  Colorado,  United States; Recruiting
Ohio
      Cleveland Clinic Foundation, Cleveland,  Ohio,  44195,  United States; Recruiting
Pennsylvania
      The University of Pennsylvania Medical Center, Philadelphia,  Pennsylvania,  United States; Recruiting

Study ID Numbers:  FD-R-002016; FD-R-002016-01
Record last reviewed:  January 2002
Record first received:  January 30, 2002
ClinicalTrials.gov Identifier:  NCT00030056
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2004-11-09