Determining the Responses and Impact of Rituximab-instigated Cell Depletion on T Cells in People With SLE
Primary Purpose
Lupus Erythematosus, Systemic
Status
Withdrawn
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Rituximab
Sponsored by
About this trial
This is an interventional treatment trial for Lupus Erythematosus, Systemic
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of SLE
- Positive ANA with a titer of at least 1:160
- Active disease (one or more modified BILAG A or B) or inability to lower steroids to leass than 20 mg/day. More information about this criterion can be found in the protocol.
- For females, must agree to use effective birth control methods for the duration of the study
Exclusion Criteria:
- Severe thrombocytopenia
- Active, moderate, or severe proliferative glomerulonephritis
- Active CNS manifestations due to lupus other than migraines, mild cognitive dysfunction, or mood disorders. More information about this criterion can be found in the protocol.
- Poorly controlled anti-phospholipid syndrom
- Significant organ dysfunction
- Conditions, other than SLE, that are likely to require prolonged systemic steroids
- Chronic infections. More information about this criterion can be found in the protocol.
- Hepatitis B infection
- Hepatitis C infection
- Deep space infection within two years of study entry
- Severe bacterial infection within three months of study entry
- More than one severe bacterial infection within two years of study entry
- Positive purified protein derivative tuberculin skin test
- History of cancer, not including basal cell carcinomas and carcinoma in situ of the cervix with documentation of successful treatment
- Alcohol or drug abuse
- Surgery within three months of study entry
- Immunization with a live vaccine within two months of study entry
- Any immunization within one month of study entry
- Received cyclophosphamide or calcineurin inhibitors within six months of study entry
- Received anti-TNF alpha antibody within 3 months of study entry
- Received etanercept within one month of study entry
- Received anti-CD20 antibodies or other lymphocyte depleting antibodies
- Received Immunoglobin G infusion protein or monoclonal antibody
- Treatment with FDA non-approved agents within six months of study entry
- Transaminases greater than two times the upper limit of normal
- Pregnant or breastfeeding
Sites / Locations
- University of Alabama at Birmingham
- University of Rochester
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Rituximab
Arm Description
Participants will receive an intravenous infusion of rituximab on Days 0 and 14
Outcomes
Primary Outcome Measures
Ratio of B and T cell subsets among those with and without a long-term response and those with and without baseline anti-RBP antibody
Secondary Outcome Measures
Impact of prolonged B cell absence on the composition and activation status of helper T cell subsets and regulatory T cells
Effect of B cell depletion on interferon-alpha activity
Full Information
NCT ID
NCT01702038
First Posted
October 3, 2012
Last Updated
October 4, 2012
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
1. Study Identification
Unique Protocol Identification Number
NCT01702038
Brief Title
Determining the Responses and Impact of Rituximab-instigated Cell Depletion on T Cells in People With SLE
Official Title
Rituximab in SLE: Understanding of Long-term Responses and the Impact of B Cell Depletion on T Cells
Study Type
Interventional
2. Study Status
Record Verification Date
October 2012
Overall Recruitment Status
Withdrawn
Study Start Date
September 2009 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to determine how B cell subsets and autoantibodies are related to disease remission after rituximab treatment in subjects with Systemic Lupus Erythematosus (SLE).
Detailed Description
Immune cells are an important part of the abnormal autoimmune response in SLE. The B cell is a significant part of this autimmune response because it produces the antibodies which can react with normal tissue of the body. B cells have the ability to accumulate and promote the development of SLE. The purpose of this study is to determine how B cell subsets and autoantibodies are related to disease remission after rituximab treatment in subjects with SLE.
This study will last approximately two years and consist of 15 study visits. These visits will occur at screening, baseline, Days 0 and 14, and Months 1, 2, 3, 4, 6, 9, 12, 15, 18, 21, and 24. Participants will receive a single rituximab injection on Days 0 and 14. Medication history and blood tests will occur at every study visit. A physical exam, medical history, and urine tests will occur at most visits. For females, a pregnancy test will occur at selected visits.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lupus Erythematosus, Systemic
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Rituximab
Arm Type
Experimental
Arm Description
Participants will receive an intravenous infusion of rituximab on Days 0 and 14
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
1000 mg administered intravenously
Primary Outcome Measure Information:
Title
Ratio of B and T cell subsets among those with and without a long-term response and those with and without baseline anti-RBP antibody
Time Frame
Day 0 through month 24
Secondary Outcome Measure Information:
Title
Impact of prolonged B cell absence on the composition and activation status of helper T cell subsets and regulatory T cells
Time Frame
Day 0 through month 24
Title
Effect of B cell depletion on interferon-alpha activity
Time Frame
Day 0 through month 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
19 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosis of SLE
Positive ANA with a titer of at least 1:160
Active disease (one or more modified BILAG A or B) or inability to lower steroids to leass than 20 mg/day. More information about this criterion can be found in the protocol.
For females, must agree to use effective birth control methods for the duration of the study
Exclusion Criteria:
Severe thrombocytopenia
Active, moderate, or severe proliferative glomerulonephritis
Active CNS manifestations due to lupus other than migraines, mild cognitive dysfunction, or mood disorders. More information about this criterion can be found in the protocol.
Poorly controlled anti-phospholipid syndrom
Significant organ dysfunction
Conditions, other than SLE, that are likely to require prolonged systemic steroids
Chronic infections. More information about this criterion can be found in the protocol.
Hepatitis B infection
Hepatitis C infection
Deep space infection within two years of study entry
Severe bacterial infection within three months of study entry
More than one severe bacterial infection within two years of study entry
Positive purified protein derivative tuberculin skin test
History of cancer, not including basal cell carcinomas and carcinoma in situ of the cervix with documentation of successful treatment
Alcohol or drug abuse
Surgery within three months of study entry
Immunization with a live vaccine within two months of study entry
Any immunization within one month of study entry
Received cyclophosphamide or calcineurin inhibitors within six months of study entry
Received anti-TNF alpha antibody within 3 months of study entry
Received etanercept within one month of study entry
Received anti-CD20 antibodies or other lymphocyte depleting antibodies
Received Immunoglobin G infusion protein or monoclonal antibody
Treatment with FDA non-approved agents within six months of study entry
Transaminases greater than two times the upper limit of normal
Pregnant or breastfeeding
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ignacio Sanz, MD
Organizational Affiliation
University of Rochester
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
John Looney, MD
Organizational Affiliation
University of Rochester
Official's Role
Study Chair
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
University of Rochester
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
17214580
Citation
Eisenberg R. Targeting B cells in SLE: the experience with rituximab treatment (anti-CD20). Endocr Metab Immune Disord Drug Targets. 2006 Dec;6(4):345-50. doi: 10.2174/187153006779025757.
Results Reference
background
PubMed Identifier
18095917
Citation
Pego-Reigosa JM, Isenberg DA. Systemic lupus erythematosus: pharmacological developments and recommendations for a therapeutic strategy. Expert Opin Investig Drugs. 2008 Jan;17(1):31-41. doi: 10.1517/13543784.17.1.31.
Results Reference
background
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Determining the Responses and Impact of Rituximab-instigated Cell Depletion on T Cells in People With SLE
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