Pilot Trial to Assess Effect of CNI Conversion of Efalizumab on T Reg Cells

• ClinicalTrials.gov Identifier: NCT00777400
• Recruitment Status: Withdrawn
• First Posted: October 22, 2008
• Last Update Posted: May 14, 2013
• Sponsor: University of California, San Francisco
• Collaborator: Genentech, Inc.
• Information provided by (Responsible Party): University of California, San Francisco

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Autoimmune Diseases	Drug: Efalizumab	Phase 1; Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Official Title: A Pilot Trial to Assess the Effect of CNI Conversion to Efalizumab in T Regulatory Cells in Renal Transplantation
• Study Start Date: December 2008
• Actual Primary Completion Date: April 2009
• Actual Study Completion Date: April 2009

Arms and Interventions

Arm

Intervention/treatment

Experimental: 1; Efalizumab will be started on Day 0 until the end of the study at Week 24. At the end of the first week, after efalizumab is started, cyclosporine or tacrolimus will be decreased by 50% and at 2 weeks the dose of cyclosporine or tacrolimus will be completely discontinued. At 12 weeks Cellcept or myfortic will be discontinued and the patient will be converted to sirolimus for the remainder of the study.

Drug: Efalizumab; 1 mg/kg of efalizumab administered sub q once weekly

Outcome Measures

Primary Outcome Measures :

1. To determine if the combination of efalizumab and sirolimus results in a significant increase in T regulatory cells. [ Time Frame: Month 6 ]

Secondary Outcome Measures :

1. The successful conversion from CNI to non-CNI regimen without increasing the rejection rate by more than 20%. [ Time Frame: 6 Months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, California

University of California, San Francisco

San Francisco, California, United States, 94143

Sponsors and Collaborators

University of California, San Francisco

Genentech, Inc.

Investigators

• Principal Investigator: Flavio Vincenti, M.D.; University of California, San Francisco

More Information

Publications of Results:

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.

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.

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.

• Responsible Party: University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT00777400
• Other Study ID Numbers: ACD4520 Efalizumab; ACD4520
• First Posted: October 22, 2008
• Last Update Posted: May 14, 2013
• Last Verified: May 2013

Keywords provided by University of California, San Francisco:

Kidney transplant; T regulatory cells; Efalizumab; Rejection; Safely convert renal transplant from mycophenolate mofetil and Calcineurin inhibitor to efalizumab and sirolimus

Additional relevant MeSH terms:

Autoimmune Diseases; Immune System Diseases