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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Withdrawn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
Northwell Health
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lupus Nephritis focused on measuring Lupus Membranous Nephritis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

    First Posted
    May 22, 2009
    Last Updated
    May 13, 2015
    Sponsor
    Northwell Health
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    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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