Immunophenotyping of Peripheral T Cells After T Cell Depletion With Alemtuzumab

Immunophenotyping and Functional Profiles of Peripheral Lymphocytes in Renal Transplant Recipients After T-cell Depletion With Alemtuzumab (Anti-CD52 Monoclonal Antibody)-Potential Implications for Safe Immunosuppressive Minimization

The purpose of this study is to check the T and B cells of the immune system in 50 newly transplanted patients whom have received a kidney (50 recipients and 50 donors totaling 100 anticipated participants). This will be done to see how the Standard of Care (SOC) anti-rejection medication, Alemtuzumab (Campath 1-H®) affects these cells- Campath 1-H® reduces the number of T cells produced by one's body.

Study Overview

• Status: Terminated
• Conditions: Kidney Transplant
• Intervention / Treatment: Drug: Alemtuzumab

Detailed Description

The purpose of this study is to check the T and B cells of the immune system in 50 newly transplanted patients whom have received a kidney (50 recipients and 50 donors totaling 100 anticipated participants). This will be done to see how the Standard of Care (SOC) anti-rejection medication, Alemtuzumab (Campath 1-H®) affects these cells- Campath 1-H® reduces the number of T cells produced by one's body. We will look for these cells using a number of laboratory tests; It will require the subjects to each give 65mL of blood at each of the 3 visits that occur during phase 1. Up to 12 subjects will be chosen from phase 1 to participate in phase 2 depending on lab results.

In phase 2, subjects will be randomized to one of the three following groups:

Group one: Continue normal immunosuppression with tacrolimus and Cellcept® (control group)

Group two: Cellcept® will be tapered down to 70% in three months. Tacrolimus will be continued at the same dosage.

Group three: Tacrolimus will be reduced to 70% in three months. Cellcept® will be continued at the same dosage.

There will be an analysis of these cells at different time point, pre and post kidney transplant. The data collection will allow us to study the stability over time of particular phenotypes (cell structures) and T cell function. We will also evaluate how the two different "minimizing protocols" effect the cell structure. Results from laboratory testing may allow us to define certain criteria that can be broadly applied in solid organ transplant recipients. This may allow for safe reduction of the anti-rejection medication that transplant recipients receive.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adult subjects between ages 18-65 years old of either gender
2. Recipients have an available ABO compatible living donor for transplant
3. Subjects are listed to be a single-organ transplant recipient (kidney only)
4. Subjects have the ability to provide informed consent

Exclusion Criteria:

1. Subjects have panel reactive antibody greater than 35%
2. Subjects have the potential to have a high recurrence rate of their primary renal disease (i.e. Focal Segmental Glomerulonephritis )
3. Subjects who have a history of Hepatitis C
4. Subjects who have had a previous organ transplant
5. Subjects are unable to fully understand the purpose of the study, thereby unable to give a fully informed consent
6. Subjects with a positive lymphocytotoxic crossmatch using donor lymphocytes and recipient serum
7. Subjects who are pregnant or nursing
8. Subjects who, due to the existence of a surgical, medical or psychiatric condition, other than the current transplant, which in the opinion of the investigator, precludes enrollment into this trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase I: Alemtuzumab; During Phase I Portion: Each kidney transplant recipient received one 30mg dose (IV push)of Alemtuzmab in the operating room per Standard of Care.	Drug: Alemtuzumab; All kidney transplant recipients received one 30mg dose (IV push) of Alemtuzumab in operating room per Standard of Care.; Other Names: Campath 1-H®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Effect of T Cell Depletion on Phenotypic & Functional Profiles of Peripheral Blood Mononuclear Cells in Steroid-free Kidney Transplant Recipients.	Blood was collected to assess peripheral blood leukocytes prior to kidney transplant, 6 months & 12 months post-transplant as follows: to obtain absolute count of circulating CD4, CD8 positive T cells, B cells & NK cells, naive & memory cells (CD45RA, CD45RO), activated T cells (CD4/CD38, CD8/CD38), regulatory cells (CD4+ CD25+). Unfortunately blood samples were lost due to malfunction of liquid nitrogen tank that stopped working during a power loss.	Pre-transplant, 6months & 12 months post-transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Donor Specific Hypo-reactivity.	Identify, by studying recipients for development of donor specific hypo-reactivity and through immunopathologic analysis of renal allograft biopsies, immunologically stable renal transplant patients in whom immunosuppression can be safely minimized. Unfortunately this secondary outcome was not studied because of lost samples that did not allowed us further analysis to identify patients with donor specific hypo reactivity.	Pre-transplant, 6mo & 12mo post-transplant

Collaborators and Investigators

• Sponsor: Northwestern University
• Collaborators: American Society of Transplant Surgeons
• Investigators: Principal Investigator: Lorenzo Gallon, MD, Northwestern University, Northwestern Memorial Hospital, Northwestern Medical Faculty Foundation

Study record dates

Study Major Dates

• Study Start: February 1, 2006
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: September 30, 2010
• First Submitted That Met QC Criteria: September 30, 2010
• First Posted (Estimate): October 4, 2010

Study Record Updates

• Last Update Posted (Actual): April 10, 2019
• Last Update Submitted That Met QC Criteria: March 27, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Antineoplastic Agents; Antineoplastic Agents, Immunological; Alemtuzumab
• Other Study ID Numbers: STU00011048