Rituximab for Anti-cytokine Autoantibody-Associated Diseases

NCT01842386 | Completed Phase 1 FDA Drug

• 2 other identifiers: 13008213-I-0082
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

Background:

• Healthy people have white blood cells that protect them against bacteria, viruses, and fungi. However, some people have diseases which cause the body to make white blood cells that do not work properly. These white blood cells can attack the body s own proteins. These types of diseases are called anti-cytokine autoantibody-associated diseases. They can cause severe illnesses and even death. They are also difficult to treat with standard drugs.
• Rituximab is a drug used to treat rheumatoid arthritis. It attacks white blood cells that do not work properly. Currently, it is not approved for treating anti-cytokine autoantibody-associated diseases. However, researchers think that it may be able to help treat people with these immune diseases. Objectives: \- To see if rituximab is a safe and effective treatment for anti-cytokine autoantibody-associated diseases. Eligibility:
• Individuals at least 18 years of age who have anti-cytokine autoantibody-associated diseases.
• Participants must also be enrolled in a related immune disorder study at the National Institutes of Health. Design:
• The study will last 24 months. Participants will take rituximab for 6 months and have follow-up visits for the remaining 18 months.
• Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Other samples will be collected as needed if participants currently have an infection.
• Participants will enter the hospital for 1 week at the start of treatment. They will have four doses of rituximab given 2 days apart. This first treatment will be monitored with frequent blood tests.
• Over the next 6 months, participants will have four more doses of rituximab given about 1 month apart. Treatment will be monitored with frequent blood tests and sample collections as needed.
• There will be four follow-up study visits at 3, 6, 12, and 18 months after the last dose of rituximab.

Conditions

Pulmonary Alveolar Proteinosis (PAP); Severe Mucocutaneous Candidiasis

Keywords

Pulmonary Alveolar Proteinosis; Autoantibodies; Mucocutaneous Candidiasis; Anti-Granulocyte; Macrophage

Outcome Measures

Primary Outcomes (1)

• safe and tolerable administration of rituximab in subjects with anticytokine autoantibody-associated diseases who are refractory to conventional treatment

  safe and tolerable administration of rituximab in subjects with anticytokine autoantibody-associated diseases who are refractory to conventional treatment

  at study end

Study Arms (1)

Rituximab

EXPERIMENTAL

Adults (=18 years of age) with anticytokine autoantibodyassociated diseases who are refractory to conventional treatment and who test negative for the human immunodeficiency virus (HIV)

Drug: Rituximab

Interventions

Rituximab DRUG

Subjects will receive intravenous (IV) infusions of rituximab 1 gram on days 1 and 15, and subsequently if indicated up to once a month for 5 months (+/-5 days for each visit) starting approximately on day 42. Subjects whose infections respond positively to the treatment but then relapse may be offered additional treatment.

Rituximab

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects (greater than or equal to 18 years of age) are eligible if they meet the following criteria:
• Currently enrolled in one of the following protocols: 95-I-0066, 07-I-0033, 01-I-0202, or 93-I-0119.
• 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.
• 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.
• 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.
• Willingness to comply with study medication, visits, and procedures, as deemed necessary by the study investigator.
• Willingness to have samples stored for future research and genetic testing.
• Willingness to be hospitalized for the inpatient visits (initial doese on day 1 and day 15 will occur in the inpatient unit.
• Negative serum pregnancy test result for women of childbearing potential.

You may not qualify if:

• Subjects who meet the following criteria are not eligible to enter the study:
• HIV seropositivity.
• Active underlying malignancy, except thymoma and basal and squamous cell carcinoma.
• 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.
• Use of another investigational study agent within 8 weeks of enrollment.
• Known anaphylaxis or IgE-mediated hypersensitivity to murine proteins or any component of the study medication.
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies.
• Evidence of significant uncontrolled concomitant diseases, such as cardiovascular disease, or nervous system, pulmonary, renal, hepatic, endocrine, or gastrointestinal disorders.
• Diagnosis of an unrelated underlying immunodeficiency.
• Hepatitis B (subjects with hepatitis C are eligible to enter the study).
• Live vaccines within 1 month prior to receiving the study drug.
• Unsuitable participation as judged by the principal investigator.
• 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).

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Pulmonary Alveolar Proteinosis; Candidiasis, Chronic Mucocutaneous

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Candidiasis; Mycoses; Bacterial Infections and Mycoses; Infections; Dermatomycoses; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Christa S Zerbe, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 25, 2013
• First Posted: April 29, 2013
• Study Start: April 29, 2014
• Primary Completion: May 6, 2021
• Study Completion: May 6, 2021
• Last Updated: April 24, 2026

Record last verified: 2026-04-13

Locations

US (1)