The Effect of Rituximab on the Development of Anti-Donor Antibodies

• Status: Completed
• Trial end date: 2010-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The aim of the study is to find out if Rituximab, which is an antibody against specific white cells involved in rejection, when combined with standard anti-rejection treatment can more effectively reverse the rejection process.

Our hypothesis is that with acute rejection there is activation of B cells and the subsequent development of anti-donor antibodies that ultimately lead to graft loss. More effective therapy targeted at B cells may abort the development of anti-HLA antibodies, prevent renal injury and have a favorable effect on long-term graft outcome.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of California, San Francisco
• Collaborator: Genentech, Inc.
• Treatments: Antibodies; Immunoglobulins; Rituximab

Criteria

Inclusion Criteria:

• Recipients of a kidney transplant or kidney-pancreas transplant with predominant findings on kidney biopsy of acute rejection and the presence of as B cells by immunohistochemistry

• Patients between 18 and 65 years of age

• Patients known not to be allergic to Rituximab

• Able and willing to give written informed consent and comply with the requirements of the study protocol

• Adequate renal function as indicated by serum creatinine less than 6 mg/dL

• 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 treatment.

• Patients who have received a kidney-pancreas transplant.

• Patients who on immunohistochemistry have evidence of B cell infiltration

Exclusion Criteria:

• Patients who have undergoing multi-organ transplant except for kidney-pancreas patients.

• Patients who have been administered an experimental drug in the 3 months preceding enrollment in the study

• 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 monoclonal antibodies

• 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 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

• 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)

• 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 insitu of the cervix.

• History of psychiatric disorder being treated with medications

• Significant cardiac or pulmonary disease (including obstructive pulmonary disease) Laboratory Exclusion Criteria (at Screening)

• Hemoglobin: < 7 gm/dL

• Platelets: < 100,000/mm

• Known history of positive Hepatitis B or C serology

• Known history of positive HIV