Immunophenotyping of Peripheral T Cells After T Cell Depletion With Alemtuzumab

• Sponsor: Northwestern University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01213329
• Collaborator: American Society of Transplant Surgeons (Other)
• Enrollment: 52
• Location: 1
• Arm: 1
• Duration (Months): 37.9
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Kidney Transplant	Drug: Alemtuzumab	Phase 4

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 Design

• Study Type: Interventional
• Actual Enrollment: 52 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Phase 1: 50 subjects were to receive study intervention. If any subjects demonstrated persistent donor specific unresponsiveness at the 12 month post-transplant time point, they would proceed into Phase 2. In that phase, the unresponsive subjects would have been randomized to one of three arms that would modify their standard of care immunosuppression. None of the 50 subjects from Phase 1 demonstrated persistent donor specific unresponsiveness, therefore, phase 2 was never started.Phase 1: 50 subjects were to receive study intervention. If any subjects demonstrated persistent donor specific unresponsiveness at the 12 month post-transplant time point, they would proceed into Phase 2. In that phase, the unresponsive subjects would have been randomized to one of three arms that would modify their standard of care immunosuppression. None of the 50 subjects from Phase 1 demonstrated persistent donor specific unresponsiveness, therefore, phase 2 was never started.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: Feb 1, 2006
• Actual Primary Completion Date: Apr 1, 2009
• Actual Study Completion Date: Apr 1, 2009

Arms and Interventions

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®

Outcome Measures

Primary Outcome Measures

1. The Effect of T Cell Depletion on Phenotypic & Functional Profiles of Peripheral Blood Mononuclear Cells in Steroid-free Kidney Transplant Recipients. [Pre-transplant, 6months & 12 months post-transplant]

   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.

Secondary Outcome Measures

1. Donor Specific Hypo-reactivity. [Pre-transplant, 6mo & 12mo post-transplant]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northwestern Memorial Hospital	Chicago	Illinois	United States	60611

Sponsors and Collaborators

• Northwestern University
• American Society of Transplant Surgeons

Investigators

• Principal Investigator: Lorenzo Gallon, MD, Northwestern University, Northwestern Memorial Hospital, Northwestern Medical Faculty Foundation

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Lorenzo Gallon, Associate Professor of Medicine & Surgery, Northwestern University
• ClinicalTrials.gov Identifier: NCT01213329
• Other Study ID Numbers: STU00011048
• First Posted: Oct 4, 2010
• Last Update Posted: Apr 10, 2019
• Last Verified: Mar 1, 2019

• Additional relevant MeSH terms: Alemtuzumab

Study Results

Participant Flow

Recruitment Details	All patients were approached pre-operatively in the transplant clinic at Northwestern Memorial Hospital. Recruitment began on July 28, 2005 and lasted until April 14, 2008.
Pre-assignment Detail	The first year of the study was specimen collection only. Group assignment (phase 2) was intended to begin after 12months of sample collection and there were not any subjects who continued into phase 2. An additional pair enrolled compared to the number that started this study. This is due to a loss of samples from a processing inconsistency

Arm/Group Title	Alemtuzumab (Phase I)	Donor Comparison
Arm/Group Description	All transplant recipients received one 30mg dose (intravenous "IV" push)of Alemtuzmab in the operating room per Standard of Care.
Period Title: Screening
STARTED	25	25
COMPLETED	25	25
NOT COMPLETED	0	0
Period Title: Screening
STARTED	0	0
COMPLETED	0	0
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Alemtuzumab (Phase I)	Donor Comparison	Total
Arm/Group Description	All transplant recipients received one 30mg dose (intravenous "IV" push)of Alemtuzmab in the operating room per Standard of Care.	Total of all reporting groups
Overall Participants	26	25	51
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	26 100%	25 100%	51 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41 (22)	43 (9.46)	42 (31.46)
Sex: Female, Male (Count of Participants)
Female	5 19.2%	13 52%	18 35.3%
Male	21 80.8%	12 48%	33 64.7%
Region of Enrollment (participants) [Number]
United States	26 100%	25 100%	51 100%

Outcome Measures

1. Primary Outcome

Title	The Effect of T Cell Depletion on Phenotypic & Functional Profiles of Peripheral Blood Mononuclear Cells in Steroid-free Kidney Transplant Recipients.
Description	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.
Time Frame	Pre-transplant, 6months & 12 months post-transplant

Outcome Measure Data

Analysis Population Description

samples from 26 recipient/donor pairs were collected = 52 collected but no analysis was performed because samples were lost.

Arm/Group Title	Alemtuzumab (Phase I)
Arm/Group Description	All transplant recipients received one 30mg dose (intravenous "IV" push)of Alemtuzmab in the operating room per Standard of Care.
Measure Participants	0

2. Secondary Outcome

Title	Donor Specific Hypo-reactivity.
Description	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.
Time Frame	Pre-transplant, 6mo & 12mo post-transplant

Outcome Measure Data

Analysis Population Description

no one were analyzed due to loss of blood samples

Arm/Group Title	Donor Comparison
Arm/Group Description	The donor group served as source of PBMCs to use as stimulator for the patients that received Alemtuzumab.
Measure Participants	0

Adverse Events

Time Frame	The period in which adverse events data was collected began with the first day of enrollment and ended at the final study visit: February 2006 through April 2009.
Arm/Group Title	Alemtuzumab (Phase I)		Donor Comparison
Arm/Group Description	All transplant recipients received one 30mg dose (intravenous "IV" push)of Alemtuzmab in the operating room per Standard of Care.
All Cause Mortality
	Alemtuzumab (Phase I)		Donor Comparison
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Alemtuzumab (Phase I)		Donor Comparison
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	00/26 (0%)		00/25 (0%)
Other (Not Including Serious) Adverse Events
	Alemtuzumab (Phase I)		Donor Comparison
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	00/26 (0%)		00/25 (0%)

Limitations/Caveats

Processing of blood samples was inconsistent and lab results were questionable. Research blood specimens were in addition to Standard of Care (SOC) required blood. Most research visits were planned at the same time as SOC visits.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.