Open Label Pilot Trial of Rituximab in Lupus Membranous Nephritis
Primary Purpose
Lupus Nephritis
Status
Withdrawn
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Rituximab
Sponsored by
About this trial
This is an interventional treatment trial for Lupus Nephritis focused on measuring Lupus Membranous Nephritis
Eligibility Criteria
Inclusion Criteria:
- Age of a minimum of 18 years old
- Able and willing to give written informed consent and comply with the requirements of the study protocol
- Negative serum pregnancy test (for women of child bearing potential)
- Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for twelve months (1 year) after completion of treatment.
- Diagnosis of SLE per current ACR classification criteria (at least 4 of 11 criteria)
- Base line proteinuria >2g/24h
- Kidney biopsy within 12 months of enrollment with membranous L.N. (ISN/RPS V)
- Full dose ACE inhibition (or ARB) for a minimum of 8 weeks at day 0. Patients may be on less than full dose due to lack of tolerability
- Stable < 0.5mg/kg corticosteroid dose in the 4 weeks prior to screening (including no corticosteroid)
- Background immunosuppressives to include azathioprine, cyclosporine A, mycophenolate mofetil, methotrexate and/or an anti-malarial for > 6 months with stable dose(s) for 1 month prior to screening/enrollment will be allowed. Patients receiving cyclophosphamide and/or leflunomide will be excluded from this study.
Exclusion Criteria:
- Treatment with cyclophosphamide within 3 months of screening
- Use of high dose steroids (>0.5 mg/kg/ day) in the 4 weeks prior to screening
- ANC < 1.5 x 103
- Hemoglobin: < 8.0 gm/dL
- Platelets: < 100,000/mm
- AST or ALT >2.5 x Upper Limit of Normal unless related to primary disease.
- Positive Hepatitis B or C serology (Hep B Surface antigen and Hep C antibody)
- History of positive HIV (HIV conducted during screening if applicable)
- Treatment with any investigational agent within 4 weeks of screening or 5 half-lives of the investigational drug (whichever is longer)
- Receipt of a live vaccine within 4 weeks prior to randomization
- Previous Treatment with Rituximab (MabThera® / Rituxan®)
- Previous treatment with Natalizumab (Tysabri®)
- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
- History of recurrent significant infection or history of recurrent bacterial infections
- Known active bacterial, viral fungal mycobacterial, or other infection (including tuberculosis or atypical mycobacterial disease, but excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with i.v. antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening
- Ongoing use of high dose steroids (>0.5 mg/kg/ day ) or unstable steroid dose in the past 4 weeks
- Lack of peripheral venous access
- History of drug, alcohol, or chemical abuse within 6 months prior to screening
- Pregnancy (a negative serum pregnancy test should be performed for all women of childbearing potential within 7 days of treatment) or lactation
- Concomitant malignancies or previous malignancies, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
- History of psychiatric disorder that would interfere with normal participation in this protocol
- Significant cardiac or pulmonary disease (including obstructive pulmonary disease)
- Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
- Inability to comply with study and follow-up procedures
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Rituximab
Arm Description
Subjects receive rituximab in an open label manner
Outcomes
Primary Outcome Measures
Efficacy at 6 months post treatment and durability of response at 12 months post treatment will be determined by: reduction in 24 hour urinary protein excretion, reciprocal creatinine, urinary sediment
Secondary Outcome Measures
Change from baseline at 6 and 12 months in non-renal SLE disease activity (BILAG), lupus serologies (anti-dsDNA antibodies) and complement consumption (C3, C4), serum albumin, cholesterol, triglycerides
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00908986
Brief Title
Open Label Pilot Trial of Rituximab in Lupus Membranous Nephritis
Official Title
Open Label Pilot Trial of Rituximab in Lupus Membranous Nephritis
Study Type
Interventional
2. Study Status
Record Verification Date
May 2015
Overall Recruitment Status
Withdrawn
Why Stopped
Terminated by sponsor
Study Start Date
December 2008 (undefined)
Primary Completion Date
November 2009 (Actual)
Study Completion Date
November 2009 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Northwell Health
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The objective of this study is to assess the as efficacy of rituximab as induction therapy in membranous lupus nephritis. Safety and tolerability will additionally be assessed. Subjects will receive open-label 2 courses of rituximab at baseline and at 6 months. They will be followed monthly for 18 months to assess response and durability of response.
The hypothesis: B cell depletion will be an effective safe and well tolerated treatment for membranous lupus nephritis (Class V).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lupus Nephritis
Keywords
Lupus Membranous Nephritis
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Rituximab
Arm Type
Experimental
Arm Description
Subjects receive rituximab in an open label manner
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Rituxan
Intervention Description
375mg/m2 q week x 4; repeated in 6 months
Primary Outcome Measure Information:
Title
Efficacy at 6 months post treatment and durability of response at 12 months post treatment will be determined by: reduction in 24 hour urinary protein excretion, reciprocal creatinine, urinary sediment
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Change from baseline at 6 and 12 months in non-renal SLE disease activity (BILAG), lupus serologies (anti-dsDNA antibodies) and complement consumption (C3, C4), serum albumin, cholesterol, triglycerides
Time Frame
12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age of a minimum of 18 years old
Able and willing to give written informed consent and comply with the requirements of the study protocol
Negative serum pregnancy test (for women of child bearing potential)
Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for twelve months (1 year) after completion of treatment.
Diagnosis of SLE per current ACR classification criteria (at least 4 of 11 criteria)
Base line proteinuria >2g/24h
Kidney biopsy within 12 months of enrollment with membranous L.N. (ISN/RPS V)
Full dose ACE inhibition (or ARB) for a minimum of 8 weeks at day 0. Patients may be on less than full dose due to lack of tolerability
Stable < 0.5mg/kg corticosteroid dose in the 4 weeks prior to screening (including no corticosteroid)
Background immunosuppressives to include azathioprine, cyclosporine A, mycophenolate mofetil, methotrexate and/or an anti-malarial for > 6 months with stable dose(s) for 1 month prior to screening/enrollment will be allowed. Patients receiving cyclophosphamide and/or leflunomide will be excluded from this study.
Exclusion Criteria:
Treatment with cyclophosphamide within 3 months of screening
Use of high dose steroids (>0.5 mg/kg/ day) in the 4 weeks prior to screening
ANC < 1.5 x 103
Hemoglobin: < 8.0 gm/dL
Platelets: < 100,000/mm
AST or ALT >2.5 x Upper Limit of Normal unless related to primary disease.
Positive Hepatitis B or C serology (Hep B Surface antigen and Hep C antibody)
History of positive HIV (HIV conducted during screening if applicable)
Treatment with any investigational agent within 4 weeks of screening or 5 half-lives of the investigational drug (whichever is longer)
Receipt of a live vaccine within 4 weeks prior to randomization
Previous Treatment with Rituximab (MabThera® / Rituxan®)
Previous treatment with Natalizumab (Tysabri®)
History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
History of recurrent significant infection or history of recurrent bacterial infections
Known active bacterial, viral fungal mycobacterial, or other infection (including tuberculosis or atypical mycobacterial disease, but excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with i.v. antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening
Ongoing use of high dose steroids (>0.5 mg/kg/ day ) or unstable steroid dose in the past 4 weeks
Lack of peripheral venous access
History of drug, alcohol, or chemical abuse within 6 months prior to screening
Pregnancy (a negative serum pregnancy test should be performed for all women of childbearing potential within 7 days of treatment) or lactation
Concomitant malignancies or previous malignancies, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
History of psychiatric disorder that would interfere with normal participation in this protocol
Significant cardiac or pulmonary disease (including obstructive pulmonary disease)
Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
Inability to comply with study and follow-up procedures
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Cynthia Aranow, MD
Organizational Affiliation
Feinstein Institute for Medical Research
Official's Role
Principal Investigator
12. IPD Sharing Statement
Learn more about this trial
Open Label Pilot Trial of Rituximab in Lupus Membranous Nephritis
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