Prospective Trial of Rituximab for Primary Pulmonary Alveolar Proteinosis

The goal of this study is to conduct a prospective, open-label 6-month trial of rituximab in
patients who present with symptomatic primary or idiopathic PAP. A total of 10 subjects with
primary PAP will be enrolled over 12 months at East Carolina University. Patients over age
18 with a clinical diagnosis of moderate symptomatic idiopathic PAP, established by
appropriate clinical history, radiographic and physiologic findings, presence of circulating
anti-GM-CSF antibody, and confirmatory findings on bronchoscopy with bronchoalveolar lavage
and/or open-lung biopsy will be recruited. Patients with newly diagnosed PAP or established
disease may be considered for this study.

Inclusion Criteria:

- Diagnosis of primary PAP (new or chronic) with presence of anti-GM-CSF antibody

- Moderately symptomatic disease with PaO2 <70 on room air and on less than 6 L/min
oxygen

- Able to give written informed consent and comply with the requirements of the study

- Adequate renal and liver function

- Negative serum pregnancy test (for women of child bearing age) and on acceptable
birth control during and after study completion

Exclusion Criteria:

- Severe PAP and requires in-patient care and more urgent therapy with bilateral whole
lung lavage

- Treatment with any investigational agent within 4 weeks of screening

- History of severe allergic or anaphylactic reactions to humanized or murine
monoclonal antibodies

- History of HIV, recurrent significant infection or recurrent bacterial infections

- Known active bacterial, viral, fungal, mycobacterial, or other infection

- Ongoing use of high dose steroids (>10mg/day) or unstable steroid dose

- Significant cardiac or pulmonary disease or blood disorder