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

Completed · Phase 2

Conditions studied: Graft Rejection, Kidney Disease

In brief

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.

Key facts

Study ID

NCT00001984

Run by

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

People needed

5

Starts

1999-11-01

Expected to finish

2008-06-01

Last updated by the study team

2016-10-27

Who can join

Age: any. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

• Immunosuppressive drug therapy at the time of or 2 months prior to enrollment. Specifically, candidates must not be taking prednisone, cyclosporine, tacrolimus, azathioprine, mycophenolate mofetil, antilymphocyte agents, cyclophosphamide, methotrexate, or other agents whose therapeutic effect is immunosuppressive.
• Any condition that precludes serial follow-up.
• Any active malignancy or any history of a hematogenous malignancy or lymphoma. Patients with primary, cutaneous basal cell or squamous cell cancers may be enrolled providing the lesions are appropriately treated prior to transplant.
• Significant coagulopathy or requirement for anticoagulation therapy that would contraindicate protocol allograft biopsies.
• Platelet count less than 100,000/mm(3).
• Hemoglobin less than 9.0 mg/dl. Patients may be on erythropoietin therapy, but will not be placed on therapy solely to facilitate research sample acquisition.
• Any known immunodeficiency syndrome.
• HLA identical status with a living donor.
• Any history of uncompensated cardiac insufficiency, major vascular disease, or symptomatic coronary artery disease.
• Systemic or pulmonary edema.
• Inability to be effectively dialyzed.
• Chronic hypotension (SBP less than 100 mmHg).
• Any condition that would likely increase the risk of protocol participation or confound the interpretation of the data.
• CMV negative status receiving an organ from a known CMV positive donor.
• EBV negative status receiving an organ from a known EBV positive donor.
• Panel reactive antibody greater than 20% due to HLA antibodies.

Where it is running

• National Institutes of Health Clinical Center, 9000 Rockville Pike — Bethesda, Maryland, United States

Full record on ClinicalTrials.gov

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