Clinical trial NCT00777400: Pilot Trial to Assess Effect of CNI Conversion of Efalizumab on T Reg Cells
Official title: A Pilot Trial to Assess the Effect of CNI Conversion to Efalizumab in T Regulatory Cells in Renal Transplantation
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Autoimmune Diseases
Keywords: Kidney transplant
T regulatory cells
Efalizumab
Rejection
Safely convert renal transplant from mycophenolate mofetil and Calcineurin inhibitor to efalizumab and sirolimus
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2008-10-22
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP

Brief summary: The purpose of this pilot trial is to determine whether a conversion from calcineurin inhibitors (CNI) and mycophenolate mofetil (MMF) to a regimen consisting of efalizumab and sirolimus is associated with an increase in T regulatory cells, white cells that control the immune system and can prevent autoimmune diseases like arthritis or rejection of foreign organs,and does not result in an increase in acute rejection.

Detailed description: The objective of this pilot trial is to determine whether the conversion from calcineurin inhibitors (CNI) and mycophenolate mofetil (MMF) to efalizumab and sirolimus is associated with an increase in T regulatory cells and does not result in an increase in acute rejection following conversion. CNIs are associated with progressive nephrotoxicity, increased cardiovascular risk factor as well as an inhibitory effect on T regulatory cells.

PRIMARY OBJECTIVE:

To determine if the combination of efalizumab and sirolimus results in a significant increase in T regulatory cells. A hundred percent increase in T regulatory cells will be determined to be an important biologic effect of the combination of efalizumab and sirolimus.

SECONDARY OBJECTIVES:

To assess the feasibility of the conversion from CNI/MMF to efalizumab/sirolimus and to determine that this combination is safe and effective

To determine if there is an increase in FoxP3 mRNA in the urine of converted patients. Urine FoxP3 is believed to correlate with T regs in the kidney.

Eligibility criteria: Inclusion Criteria:

* Ability to provide written informed consent and comply with study assessments for the full duration of the study.
* Male or female, 18-70 years
* Recipients of primary renal transplants from living and deceased donors
* Stable renal function for 4 weeks prior to entry into the study
* No history of acute rejection
* Pretransplant negative crossmatch
* Hematocrit \>30% at the time of inclusion, platelet count \>100,000 and WBC ≥ 3.0
* If a female of childbearing potential, a negative pregnancy test and commitment to the use of two forms of effective contraception (birth control) for the duration of the study are necessary.
* If a non-sterile male, commitment to the use of two forms of effective contraception (birth control) for the duration of the study is necessary.

Exclusion Criteria:

* Patients with known hypersensitivity to Raptiva® (efalizumab) or any of its components.
* Pregnant or lactating women
* Pretransplant PRA \>20%
* cGFR \< 35/ml/min
* \>500 mg protein as estimated by spot protein/creatinine ratio
* Recipients of other organ transplants
* Subject has a current malignancy or a history of malignancy, except non-metastatic basal or squamous cell carcinoma of the skin that has been treated successfully.
* Patients receiving experimental immunosuppressive agents
* Prior enrollment in the study
* Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated.
* Participation in another simultaneous medical investigation or trial

Primary outcomes:
measure: To determine if the combination of efalizumab and sirolimus results in a significant increase in T regulatory cells.
timeFrame: Month 6
Secondary outcomes:
measure: The successful conversion from CNI to non-CNI regimen without increasing the rejection rate by more than 20%.
timeFrame: 6 Months
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
Study officials:
affiliation: University of California, San Francisco
name: Flavio Vincenti, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nankivell BJ, Borrows RJ, Fung CL, O'Connell PJ, Allen RD, Chapman JR. The natural history of chronic allograft nephropathy. N Engl J Med. 2003 Dec 11;349(24):2326-33. doi: 10.1056/NEJMoa020009.
citation: Meier-Kriesche HU, Schold JD, Srinivas TR, Kaplan B. Lack of improvement in renal allograft survival despite a marked decrease in acute rejection rates over the most recent era. Am J Transplant. 2004 Mar;4(3):378-83. doi: 10.1111/j.1600-6143.2004.00332.x.
citation: Vincenti F, Mendez R, Pescovitz M, Rajagopalan PR, Wilkinson AH, Butt K, Laskow D, Slakey DP, Lorber MI, Garg JP, Garovoy M. A phase I/II randomized open-label multicenter trial of efalizumab, a humanized anti-CD11a, anti-LFA-1 in renal transplantation. Am J Transplant. 2007 Jul;7(7):1770-7. doi: 10.1111/j.1600-6143.2007.01845.x.