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Effectiveness of the Investigational Drug Campath-1H in Preventing Rejection of Transplanted Kidneys

NCT00001984 · Status: COMPLETED · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 5

Last updated 2016-10-27

Study results available
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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.

Conditions

Interventions

DRUG

Alemtuzumab and DSG

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.

Sponsors & Collaborators

  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

    lead NIH

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
1999-11-30
Primary Completion
2008-06-30
Completion
2008-06-30

Countries

  • United States

Study Locations

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Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT00001984 on ClinicalTrials.gov