Determining the Responses and Impact of Rituximab-instigated Cell Depletion on T Cells in People With SLE

This study has been withdrawn prior to enrollment.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01702038
First received: October 3, 2012
Last updated: October 4, 2012
Last verified: October 2012
  Purpose

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).


Condition Intervention Phase
Lupus Erythematosus, Systemic
Drug: Rituximab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Rituximab in SLE: Understanding of Long-term Responses and the Impact of B Cell Depletion on T Cells

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

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 [ Time Frame: Day 0 through month 24 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • Effect of B cell depletion on interferon-alpha activity [ Time Frame: Day 0 through month 24 ] [ Designated as safety issue: Yes ]

Enrollment: 0
Study Start Date: September 2009
Arms Assigned Interventions
Experimental: Rituximab
Participants will receive an intravenous infusion of rituximab on Days 0 and 14
Drug: Rituximab
1000 mg administered intravenously

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.

  Eligibility

Ages Eligible for Study:   19 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01702038

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, New York
University of Rochester
Rochester, New York, United States, 14642
Sponsors and Collaborators
Investigators
Study Chair: Ignacio Sanz, MD University of Rochester
Study Chair: John Looney, MD University of Rochester
  More Information

Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01702038     History of Changes
Other Study ID Numbers: DAIT ALE01
Study First Received: October 3, 2012
Last Updated: October 4, 2012
Health Authority: United States: Food and Drug Administration
United States: Federal Government

Additional relevant MeSH terms:
Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Rituximab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 26, 2014