Rituximab for Pediatric Renal Transplant Rejection

Inclusion Criteria:Patients must meet the following inclusion criteria to be eligible forstudy entry:

• Pediatric renal allograft recipients aged 2-21 years with biopsy proven acuterejection episodes.

• Able and willing to give written informed consent and comply with the requirements ofthe study protocol (patients >18 years of age or parents)

• Greater than 30% decline in baseline renal function as indicated by a rise in theserum creatinine.

• Adequate liver function, as indicated by AST or ALT <2x upper limit of normal unlessrelated to primary disease.

• Negative serum pregnancy test (for women of child bearing age)

• Men and women of reproductive potential must agree to use an acceptable method ofbirth control during treatment and for twelve months (1 year) after completion oftreatment.&#xA;

Exclusion Criteria:Patients will be excluded from the study based on the followingcriteria:

• Treatment with any investigational agent within 4 weeks of screening or 5 half-livesof the investigational drug (whichever is longer)

• Receipt of a live vaccine within 4 weeks prior to randomization

• Previous Treatment with Rituximab (MabThera® / Rituxan®)

• History of severe allergic or anaphylactic reactions to humanized or murine monoclonalantibodies

• History of HIV (positive HIV, HIV conducted during screening if applicable)

• History of Hepatitis B and/or Hepatitis C (Hep B/C at screening)

• History of recurrent significant infection or history of recurrent bacterialinfections

• Known active bacterial, viral, fungal, mycobacterial, or other infection (includingtuberculosis or atypical mycobacterial disease, but excluding fungal infections ofnail beds) or any major episode of infection requiring hospitalization or treatmentwith IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeksprior to screening

• Ongoing use of high dose steroids (>10mg/day) or unstable steroid dose in the past 4weeks.

• 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 ofchildbearing potential within 7 days of treatment) or lactation

• Concomitant malignancies or previous malignancies within the last five years, with theexception of adequately treated basal or squamous cell carcinoma of the skin orcarcinoma in situ of the cervix.

• History of psychiatric disorder

• Significant cardiac or pulmonary disease (including obstructive pulmonary disease)

• Any other disease, metabolic dysfunction, physical examination finding, or clinicallaboratory finding giving reasonable suspicion of a disease or condition thatcontraindicates the use of an investigational drug or that may affect theinterpretation of the results or render the patient at high risk from treatmentcomplications

• Inability to comply with study and follow-up procedures