Open Label Pilot Trial of Rituximab in Lupus Membranous Nephritis

NCT00908986 | Withdrawn DMC

• 1 other identifier: U2971g
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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).

Conditions

Lupus Nephritis

Keywords

Lupus Membranous Nephritis

Outcome Measures

Primary Outcomes (1)

• 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

  12 months

Secondary Outcomes (1)

• 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

  12 months

Study Arms (1)

Rituximab

EXPERIMENTAL

Subjects receive rituximab in an open label manner

Drug: Rituximab

Interventions

Rituximab DRUG

375mg/m2 q week x 4; repeated in 6 months

Also known as: Rituxan

Rituximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Northwell Health: lead

MeSH Terms

Conditions

Lupus Nephritis

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lupus Erythematosus, Systemic; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Cynthia Aranow, MD

  Feinstein Institute for Medical Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: May 22, 2009
• First Posted: May 27, 2009
• Study Start: December 1, 2008
• Primary Completion: November 1, 2009
• Study Completion: November 1, 2009
• Last Updated: May 14, 2015

Record last verified: 2015-05