Rituximab will be tested for its safety and potential efficacy in treating B cell dense
renal allograft rejection episodes in children receiving renal transplants at Stanford
Twenty kidney transplant recipients who are being cared for at Stanford University and UCLA
and are between the ages of 2-21, can be considered for participation in this research if
they are having an acute rejection episode. After a biopsy is done and the diagnosis of
acute rejection is made, ten patients will be randomly enrolled in the group to be treated
with Rituximab and steroid pulses. Ten children will be enrolled as the control group,
receiving standard of care for acute transplant rejection.
Assignment will be based on a 1:1 randomization scheme. That means two patients will be
assigned to the group of patients receiving steroid pulsing and 4 doses of Rituximab. The
third patient would be assigned to the group receiving steroid pulses and adjustment in
immunosuppression medications which is the standard of care at Stanford University.
The dose of Rituximab that will be given is 375 mg/m2 and is administered through an IV.
Additional doses of Rituximab will be administered on a weekly basis. A total of four doses
will be given.
If the acute rejection does not resolve by one-week, patients in both groups have the option
of receiving polyclonal antibody therapy.
Inclusion Criteria:Patients must meet the following inclusion criteria to be eligible for
- Pediatric renal allograft recipients aged 2-21 years with biopsy proven acute
- Able and willing to give written informed consent and comply with the requirements of
the study protocol (patients >18 years of age or parents)
- Greater than 30% decline in baseline renal function as indicated by a rise in the
- Adequate liver function, as indicated by AST or ALT <2x upper limit of normal unless
related 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 of
birth control during treatment and for twelve months (1 year) after completion of
Exclusion Criteria:Patients will be excluded from the study based on the following
- 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®)
- History of severe allergic or anaphylactic reactions to humanized or murine
- 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 bacterial
- 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 IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks
prior to screening
- Ongoing use of high dose steroids (>10mg/day) or unstable steroid dose in the past 4
- 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 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)
- 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
- Inability to comply with study and follow-up procedures