Effects of Rituximab and Mycophenolate Mofetil (MMF) on Highly Sensitized Patients Awaiting Renal Transplant
Condition: Kidney Failure, Chronic; Diabetic Nephropathies; Glomerulonephritis, IGA; Hypertension, Renal
MeSH terms: Kidney Diseases; Renal Insufficiency; Diabetic Nephropathies; Kidney Failure, Chronic; Glomerulonephritis; Glomerulonephritis, IGA; Hypertension, Renal; Hypertension
Intervention: Rituximab; Mycophenolate mofetil (MMF)
Intervention description: Rituximab dose is 1,000 mg given as an IV infusion every two weeks for 2 doses (days 1 and 15).; Cellcept is continued from prior study, taken 500 - 1,000 mg BID, P.O.
Intervention MeSH terms: Mycophenolic Acid; Rituximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Dialysis; Kidney; Renal; Nephropathy; Glomerulonephropathy; Immunosuppression; Graft; Compatibility; Transplant; Diabetes; Hypertension; Transplantation, Kidney

Summary:

      This is a 12-month phase 2, prospective, open label study to evaluate the effect of rituximab
      with mycophenolate mofetil (MMF)on the PRA of 14 highly sensitized patients who just
      completed an 8 month trial of MMF treatment alone. PRA values obtained at study enrollment
      and at 6 and 12 months on combined therapy as well as the rates of transplant will be
      compared and evaluated using descriptive analysis.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age range 18 - 75, inclusive

          -  Able and willing to give written informed consent and comply with the requirements of
             the study protocol

          -  Outpatient status

          -  Patients with a Panel of Reactive Antibodies (PRA) over 10% after an 8-month trial of
             MMF monotherapy

          -  Patients with updated immunizations for tetanus, influenza, hepatitis B, pneumococcus

          -  Patients with a negative purified protein derivative(PPD ) screen for tuberculosis
             (TB)within the last 6 months. If subject has a prior history of TB or positive PPD,
             documentation of adequate treatment is required.

          -  Women who are of childbearing potential must have a negative serum pregnancy test
             prior to being enrolled in the study and agree to use a medically acceptable method of
             contraception throughout the study and for twelve months (1 year) after completion of
             treatment.

          -  Men must agree to use an acceptable method of birth control during treatment and for
             twelve months (1 year) after completion of treatment.

          -  Liver enzymes ALT and AST less than 2 times the normal limit.

        Exclusion Criteria:

          -  Active infection

          -  Receipt of live vaccine within 4 weeks prior to first infusion.

          -  Previous treatment with rituximab (MabThera® / Rituxan®)

          -  History of multiple recurrent infections defined as more than 3 urinary tract
             infections, 2 episodes of pneumonia or 3 episodes of otitis/sinusitis in one year, or
             more than two dialysis line or peritoneal infections within one year.

          -  Infection with hepatitis C virus (HCV) or hepatitis B virus(HBV) or human
             immunodeficiency virus (HIV), lack of documentation of treatment of a positive PPD,
             pregnant or breast-feeding, baseline leukopenia, white blood cell count (WBC) less
             than 4.0, thrombocytopenia (platelet count less than 100,000/mm) or difficult to treat
             anemia, a hematocrit chronically less than 32 on intravenous iron and EPO
             (erythropoietin) therapy, history of severe allergic or anaphylactic reactions to
             humanized or murine monoclonal antibodies.

          -  Concomitant malignancies or previous malignancies within the last five years, 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

          -  Significant cardiac or pulmonary disease (including obstructive pulmonary disease)