The effects of rituximab and obinutuzumab on lymphocyte subsets in peripheral blood and lymphoid tissues of SLE patients
- Conditions
- Systemic Lupus ErythematosusSLE10003816
- Registration Number
- NL-OMON56559
- Lead Sponsor
- Amsterdam UMC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 20
SLE patients who:
1. fulfill ACR 1997 and/or SLICC and/or ACR/ EULAR 2019 criteria,
2. have a SLEDAI-2K score >=6.
3. are aged between 18-75
4. are clinically determined to have severity of disease and refractoriness
that supports the off-label use of anti-CD20 therapy
- Patients who are not able to give informed consent. - Pregnancy - Severe
renal impairment (eGFR <30ml/min/1.73m2 according to CKD-EPI formula) - Present
or previous treatment with any cell depleting therapies, including anti-B-cell
therapy, belimumab or other investigational agents (e.g., abetimus sodium, anti
CD40L antibody, BG9588/ IDEC 131) in the last 3 years. Investigational agent
applies to any drug not approved for sale in the country in which it is being
used. - Intravenous cyclophosphamide 90 days prior to anti-CD20 therapy - Any
non-biologic investigational agent (investigational agent applies to any drug
not approved for sale in the country in which it is being used) 30 Days Prior
to anti-CD20 therapy (or 5 half-lives, whichever is greater) - Live vaccines
within 30 days prior to baseline or concurrently with anti-CD20 therapy -
Presence of any other disease for which study subjects need chronic or
intermittent immunosuppressive therapy (e.g. prednisolon for COPD). - History
of infection: • Currently on any suppressive therapy for a chronic infection
(such as tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus,
herpes zoster and atypical mycobacteria) • Hospitalization for treatment of
infection within 60 days of Day 0. • Use of parenteral (IV or IM) antibiotics
(anti-bacterial, antiviral, anti-fungal, or anti-parasitic agents) within 60
days of Day 0 - History of malignancies neoplasm within the last 5 years except
basal cell or squamous cell carcinoma of the skin treated with local resection
only or carcinoma in situ of the uterine cervix treated locally and with no
evidence of metastatic disease for 3 years - Have any intercurrent significant
medical or psychiatric illness that the investigator considers would make the
candidate unsuitable for the study, including evidence of serious suicide risk
including any history of suicidal behaviour in the last 6 months and/or any
suicidal ideation in the last 2 months or who in the investigator's judgment,
poses a significant suicide risk - Have a history of a primary
immunodeficiency, including significant IgG deficiency (IgG level < 400 mg/dL)
or IgA deficiency (IgA level < 10 mg/dL) - Have current drug or alcohol abuse
or dependence, or a history of drug or alcohol abuse or dependence within 365
days prior to Day 0 - Have a historically positive HIV test or test positive at
screening for HIV - Hepatitis status: • Serologic evidence of current or past
Hepatitis B (HB) infection based on the results of testing for HBsAg and HBcAb
as follows: patients positive for HBsAg or HBcAb are excluded • Positive test
for Hepatitis C antibody - Have a history of an anaphylactic reaction to
parenteral administration of contrast agents, human or murine proteins or
monoclonal antibodies - Have any other clinically significant abnormal
laboratory value in the opinion of the investigator
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The proportion of patients with depletion of total CD19+ and other B lineage<br /><br>cells in the peripheral blood (quantitative using ImmunoSeq analysis) and lymph<br /><br>nodes, defined as a decrease of >2 points on a 4-point semi-quantitative scale.<br /><br>These will be separate co-primary endpoints. We will statistically test the<br /><br>difference in the proportions of patients with depletion by these criteria in<br /><br>RTX- versus OBI-treated patients.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Correlation between CD19+ lymphocyte (and other B lineage cells) depletion in<br /><br>peripheral blood/tissues and clinical response. Depletion<br /><br>(defined as a decrease of >2 points on a 4-point semi-quantitative scale of<br /><br>CD19+ cells in the lymph node) will be related to clinical response<br /><br>(defined as a >4 point improvement in cSLEDAI or any improvement in BILAG-2004<br /><br>score) in a 2x2 chi-square test for all 20 patients.<br /><br>Further secondary and exploratory outcomes are changes in B lineage cells and<br /><br>associated (pathogenic) T cell subsets in lymph nodes and skin of SLE patients<br /><br>in comparison to the changes in the peripheral blood compartment, analyses to<br /><br>investigate whether change in B lineage cells and associated (pathogenic) T<br /><br>cell subsets in tissues is associated with clinical outcomes and/or known<br /><br>serological biomarkers such as antidsDNA and complement components C3 and C4.</p><br>