improving transplant options of highly sensitized recipients using igiv-c, 10%

Conditions: Kidney Failure, Chronic

Summary: the purpose of this study is to determine if igiv-c, 10% will be effective in converting a donor-recipient crossmatch status from positive to negative. the crossmatch test is used to determine if the donor tissue and recipient tissue are compatible. the study will also evaluate if igiv-c, 10% will allow successful kidney transplantation in a patient who otherwise would not be able to receive a transplant. three dose levels of igiv-c, 10% will be evaluated to determine what dose level is most effective.

kidney transplantation has emerged as the treatment of choice for patients with end-stage renal disease (esrd). preliminary data suggest that igiv therapy could have significant benefits in modifying allograft rejection episodes, stabilizing long-term allograft function, and reducing ischemia/reperfusion injury. qualified patients will have an in-vitro assessment of the ability of igiv-c, 10% to convert the donor-specific crossmatch (cytotoxic assay) from positive to negative. those patients with successful in-vitro conversion of the donor-specific crossmatch assay will be randomized to receive igiv-c, 10% intravenously at a dose of either 2 gm/kg, 1 gm/kg, or 0.5 gm/kg. igiv-c, 10% will be administered 3 to 5 days prior to planned transplantation and, if transplantation is successful, 7 days post-transplant. if after receiving the igiv-c infusion the donor-specific crossmatch reveals that cell death has fallen to 20% or less above background, the crossmatch will be considered negative. if after receiving one infusion the crossmatch remains positive, additional igiv-c infusions may be administered at one-month intervals, up to 4 infusions. a repeat crossmatch must be obtained after each infusion. patients will be followed for 12 months post-transplant. concomitant therapy will include a standard immunosuppression regimen of mycophenolate mofetil, tacrolimus, and prednisone following induction therapy with thymoglobulin.

Eligibility criteria:
inclusion criteria for recipient: * end-stage renal disease * no known contraindications for therapy with igiv-c, 10% * have identified a living kidney donor * positive crossmatch with the intended donor * parent or guardian willing to provide consent, if applicable exclusion criteria for recipient: * pregnant or breastfeeding * women of child-bearing age who are not willing or able to practice approved methods of contraception * hiv infection * hepatitis b or hepatitis c infection * history of positive tuberculin skin test * selective iga deficiency, known anti-iga antibodies, or history of severe allergy to any part of the clinical trial material * have received or will receive multiple organ transplants * any licensed or investigational live attenuated vaccine within 2 months of the screening visit * patients deemed unable to comply with the protocol * heart attack within 1 year of screening * history of clinically significant thrombotic episodes or active peripheral vascular disease * investigational agents within 4 weeks of study entry inclusion criteria for donor: * positive donor-specific crossmatch with the intended recipient * ecog performance status 0 or 1 * excellent health * acceptable laboratory parameters * compatible blood type * normal heart and lung evaluations * parent or guardian willing to provide consent, if applicable

Keywords: kidney transplantation transplantation, homologous hla antigens autoantibodies immunoglobulins, intravenous living donors dose-response relationship, immunologic