At a glance
ClinicalIndex Comparison Record- ✓Candidate for kidney transplant at Warren G. Magnuson Clinical Center
- ✓Willingness and legal ability to give informed consent or permission from legal guardian
- ✓Ability to travel to Clinical Center for protocol samples or send samples via overnight mail
- ✓Availability of donor tissue for testing (splenic or peripheral blood lymphocytes)
- ✕Immunosuppressive drug therapy at time of enrollment or within 2 months prior (prednisone, cyclosporine, tacrolimus, azathioprine, mycophenolate mofetil, antilymphocyte agents, cyclophosphamide, methotrexate)
- ✕Any condition that precludes serial follow-up
- ✕Active malignancy or history of hematogenous malignancy or lymphoma (except treated primary cutaneous basal cell or squamous cell cancers)
- ✕Significant coagulopathy or requirement for anticoagulation therapy that would contraindicate allograft biopsies
Standardized by ClinicalIndex from the ClinicalTrials.gov record · verify against the source.
Tolerance Induction Following Human Renal Transplantation Using Treatment With a Humanized Monoclonal Antibody Against CD52 (Campath-1H)
In Brief
A Phase 2 clinical trial evaluating Alemtuzumab and DSG for Graft Rejection and Kidney Disease. Completed, enrolled 5 participants across 1 site.
Detailed Summary
This protocol will test a humanized monoclonal antibody known as Campath-1H for its ability to induce a state of permanent allograft acceptance, or tolerance, when administered in combination with a brief course of the immunosuppressive drug deoxyspergualin (DSG) at the time of human renal allotransplantation. Campath-1H is specific for the common lymphocyte and monocyte antigen CD52. Its administration temporarily depletes mature lymphocytes and some monocytes without altering neutrophils or hematopoietic stem cells. Deoxyspergualin inhibits the NFkB pathway thus preventing monocyte and macrophage activation. Recipients of living or cadaveric donor kidneys will be treated with one dose of Campath-1H prior to transplantation to insure that peripheral depletion is achieved at the time of graft reperfusion. Three subsequent doses of Campath-1H will be administered on the first, third and fifth days after the transplant to deplete passenger donor leukocytes and residual recipient cells that mobilize in response to the allograft. In addition, patients will be treated with DSG for 14 days beginning on the day prior to surgery. This trial expands on pilot studies at the NIH of 15 patients in which Campath was given alone at the time of transplantation. In those studies, excellent peripheral depletion occurred after just one dose of Campath though central depletion required additional dosing. This allowed for greatly reduced immunosuppression to be used to prevent rejection, but to date, all patients have required some immunosuppressive medication. It is hoped that the addition of DSG will eliminate the need for long-term immunosuppression. Patients will be followed closely in the post transplant period. If patients experience rejection, they will be treated with methylprednisolone and have immunosuppression added using sirolimus as the predominant immunosuppressive agent. In the previous phase of this study without DSG, this maneuver has in all cases been successful in returning the allograft to normal function. In addition to evaluating graft function following transplantation, this protocol will also characterize and evaluate the function of the immune system and the composition of the T cell repertoire following the administration of Campath-1H and DSG, and during immune system recovery after transplantation.
Study Details
Timeline
Interventions
Alemtuzumab was administered intravenously at 0.3 mg/kg/dose over 3 hr. Patients received one dose on each of days -1,+1,+3 and +5 relative to transplantation (total dose 1.2 mg/kg). Methylprednisolone was given prior to each dose to limit the cytokine release: 500 mg prior to dose 1, 125 mg prior to dose 2, and 60 mg prior to doses 3 and 4. Deoxyspergualin was dosed as follows. The first two patients received 4 mg/kg as a loading dose on the day of transplant and 2.5 mg/kg daily for 13 additional days (14 days of treatment; 36.5 mg/kg total dose). The next three patients received the same dosing regimen but it was initiated on postoperative day 12 to coincide with the resurgence of monocytes on days 12- 25.