Rituximab for Anti-cytokine Autoantibody-Associated Diseases

This is an interventional treatment trial for Pulmonary Alveolar Proteinosis (PAP) focused on measuring Pulmonary Alveolar Proteinosis, Autoantibodies, Mucocutaneous Candidiasis, Anti-Granulocyte, Macrophage Read More

• INCLUSION CRITERIA:

Subjects (greater than or equal to 18 years of age) are eligible if they meet the following criteria:

1. Currently enrolled in one of the following protocols: 95-I-0066, 07-I-0033, 01-I-0202, or 93-I-0119.

2. Presence of anticytokine autoantibodies in serum or plasma, along with the anticipated clinical consequences of the identified anticytokine autoantibody including, but not limited to:

   • Anti-IFN- >= autoantibodies and disseminated NTM.
   • Anti-IL-17 autoantibodies and CMC.
   • Anti-GM-CSF autoantibodies and PAP or cryptococcosis.

3. Progression of anticytokine autoantibody-associated diseases despite conventional therapy, including, but not limited to:

   • Antimycobacterials for disseminated NTM.
   • Antifungals for mucocutaneous candidiasis or cryptococcosis.
   • Subcutaneous or inhaled GM-CSF and/or whole lung lavage for PAP.
4. For ongoing autoantibody-associated infection, stable, optimized antibiotic regimen for at least 1 month prior to initiation of rituximab and ability to continue these antibiotics throughout treatment with rituximab.
5. Willingness to comply with study medication, visits, and procedures, as deemed necessary by the study investigator.
6. Willingness to have samples stored for future research and genetic testing.
7. Willingness to be hospitalized for the inpatient visits (initial doese on day 1 and day 15 will occur in the inpatient unit.

8. Negative serum pregnancy test result for women of childbearing potential.

   • Women of childbearing potential and men are eligible if they agree to postpone conception for 18 months following rituximab therapy. They must agree to use 2 adequate methods of contraception, such as:
   • Hormonal contraception.
   • Male or female condoms with or without a spermicide, diaphragm or cervical cap with a spermicide, or intrauterine device.
   • Sterilization of either partner.

EXCLUSION CRITERIA:

Subjects who meet the following criteria are not eligible to enter the study:

1. HIV seropositivity.
2. Active underlying malignancy, except thymoma and basal and squamous cell carcinoma.

3. Immunomodulatory or immunosuppressive therapy, including:

   • Corticosteroids at a dose equivalent to greater than or equal to 15 mg of prednisone/day at any time during the month immediately prior to enrollment.
   • History of using biologic agents or any other systemic immune-suppressive or immunomodulatory agents within the past year.
4. Use of another investigational study agent within 8 weeks of enrollment.
5. Known anaphylaxis or IgE-mediated hypersensitivity to murine proteins or any component of the study medication.
6. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies.
7. Evidence of significant uncontrolled concomitant diseases, such as cardiovascular disease, or nervous system, pulmonary, renal, hepatic, endocrine, or gastrointestinal disorders.
8. Diagnosis of an unrelated underlying immunodeficiency.
9. Hepatitis B (subjects with hepatitis C are eligible to enter the study).
10. Live vaccines within 1 month prior to receiving the study drug.
11. Unsuitable participation as judged by the principal investigator.
12. History of cancer, including solid tumors and hematologic malignancies (except basal cell or squamous cell carcinoma of the skin that have been excised and cured and thymoma).
13. History of alcohol, drug, or chemical abuse within 6 months prior to screening.
14. Poor peripheral venous access.
15. Intolerance or contraindications to oral or IV corticosteroids.

16. Screening laboratory values:

    • Serum creatinine >1.4 mg/dL for women and >1.6 mg/dL for men.
    • Platelet count <100,000/ L.
    • Absolute neutrophil count <1500 cells/ L.
    • IgG <5.65 times 10(-2) mg/dL or IgM <0.55 times 10(-2) mg/dL.
17. Breastfeeding.