Campath-1H/Rapamycin in Renal Transplantation
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Project Summary:
We propose to test a novel combination of an antibody (Campath-1H) directed at immune cells with a relatively new drug (rapamycin) which inhibits some of the functions of immune cells. In a pilot trial at the University of Wisconsin, this drug combination has effectively prevented rejection, although it is not known whether it will prevent chronic rejection or induce tolerance.
Since it is known that tolerance is more easily achieved across a lesser immunologic barrier and more difficult to achieve across a greater immunologic disparity, we propose to test this therapy for its ability to induce tolerance first using well-matched donor-recipient pairs and progressing to greater degrees of difficulty with more poorly matched donor-recipient pairs. This trial will test the hypothesis that tolerance to renal transplants can be achieved using a combination of immune cell depletion by an antibody and partial blockade of immune cell function by a maintenance drug for a limited period of time (1 to 3 years).
Patients without evidence of rejection will be randomized to either continue or discontinue rapamycin. Patients with a perfect match with their donor kidney will be randomized at 1 year; patients with a partial mismatch (1-3 of 6 antigens) will be randomized at 2 years, and patients with a greater mismatch (4-6 of 6 antigens) will be randomized at 3 years. The rationale for stepwise rapamycin discontinuation is a) tolerance takes time to establish and probably more time is required the greater the degree of disparity (mismatch) between donor and recipient, b) the results of this tolerance trial can be first assessed in well-matched patients before putting poorly matched patients at risk of rejection.
If unsuccessful in well-matched patients, the trial would not be extended to poorly matched recipients. Even if the trial of rapamycin withdrawal (tolerance) is unsuccessful, the strategy of Campath-1H/rapamycin may represent a substantial improvement or step toward tolerance when compared to current conventional immunosuppression in organ transplantation. If acute and chronic rejection is substantially reduced, and side effects of drug therapy reduced, patients would benefit from this new strategy.
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- University of Wisconsin Department of Surgery
First published: 07/15/02 Last updated: 08/19/08
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