Immune Monitoring and CNI Withdrawal in Low Risk Recipients of Kidney Transplantation

Kidney Transplant Recipients Clinical Trial

Official title:

Immune Monitoring and Calcineurin Inhibitor (CNI) Withdrawal in Low Risk Recipients of Kidney Transplantation

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01517984
• Other study ID #: DAIT CTOT-09
• Status: Terminated
• Phase: Phase 2
• First received: January 20, 2012
• Last updated: September 11, 2015
• Start date: November 2010
• Est. completion date: May 2015

Study information

• Verified date: September 2015
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Institutional Review BoardUnited States: Data and Safety Monitoring Board
• Study type: Interventional

Clinical Trial Summary

The study will compare how well transplanted kidneys work and the response of people's immune systems as tacrolimus, a calcineurin inhibitor (CNI), is withdrawn. In addition, this research study will evaluate whether reducing immunosuppression can decrease some of these side effects while still preventing rejection of the kidney.

Description:

Kidney transplantation is a treatment option for people with kidney disease. However, there is still much to learn about how to best care for the transplanted kidney and keep it functioning for a long time. Transplant recipients take immunosuppression (anti-rejection) drugs to prevent their body from rejecting the new kidney. These drugs are used to prevent the immune system from attacking the transplanted kidney. All anti-rejection medications have unwanted side effects. The purpose of this study is to evaluate the safety of slowly removing tacrolimus, a CNI.

POST STUDY TERMINATION NOTE: Although the investigators were unable to assess the primary study end point due to early study termination,this trial supports the conclusion that risks associated with acute rejection and donor-specific antibodies outweigh any potential benefits of tacrolimus withdrawal, even in this highly selected, low-risk cohort of living donor recipients treated with antithymocyte globulin induction.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 52
• Est. completion date: May 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

INCLUSION CRITERIA -

Initial Enrollment/Screening: Patients who meet all of the following criteria are eligible for enrollment as study subjects:

• Subject must be able to understand and provide written informed consent;

• Primary living-donor (related or unrelated) kidney transplant recipients;

• Peak flow-based PRAs for class I and class II <30%(performed by local center);

• Current (within 8 weeks prior to transplantation) flow-based PRAs for class I and class II <30% (performed by local center);

• No donor specific antibody by flow solid phase method on the peak PRA serum (if serum available), or on the current PRA serum (within 8 weeks prior to transplantation) performed by central core laboratory. If the sera for the peak PRA is not available, then only the current PRA serum will be tested;

• Negative T-cell and B-cell crossmatch by flow cytometry (performed by local center);

• Female subjects of childbearing potential must have a negative pregnancy test (urine or serum) upon study entry;

• Female and male subjects with reproductive potential must agree to use FDA approved methods of birth control while participating in the study.

Inclusion Criteria for Randomization:

Participants who meet all of the following criteria are eligible for randomization:

• No history of acute rejection episodes;

• The pre-randomization protocol biopsy should confirm no rejection, including borderline rejection (based on the central pathology read);

• No donor specific antibody as detected by flow solid phase method (performed by the central core laboratory).

EXCLUSION CRITERIA -

Initial Enrollment/Screening:

Participants who meet any of these criteria are not eligible for enrollment as study subjects:

• Recipient of multiple organ transplants;

• Prior history of organ transplantation;

• Deceased-donor source;

• Any condition that would preclude protocol biopsies;

• HLA identical recipients;

• Currently breast-feeding or plans to become pregnant during the timeframe of the study follow up period;

• Any condition that, in the opinion of the investigator, would interfere with the subject's ability to comply with study requirements;

• Inability or unwillingness to comply with study protocol;

• Use of investigational drugs within 4 weeks of study entry and for the duration of the study;

• Recent recipient of any licensed or investigational live attenuated vaccine(s) within two months of prior to study entry.

Exclusion Criteria for Randomization:

Participants who meet any of these criteria are not eligible for randomization:

• Subjects who receive less than 4.5mg/kg of Rabbit ATG (Thymoglobulin®) induction therapy;

• Subjects who test positive for BKV by PCR in the blood at 6 months post-transplant;

• Any condition that would preclude protocol biopsies;

• Currently breast-feeding or plans to become pregnant during the timeframe of the study follow up period;

• Any condition that, in the opinion of the investigator, would interfere with the subject's ability to comply with study requirements;

• Inability or unwillingness of a subject to give written informed consent or comply with study protocol;

• Use of investigational drugs within 4 weeks of study entry and for the duration of the study;

• Subjects who receive less than 1500 mg daily of Mycophenolate Mofetil (CellCept®) or equivalent.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Kidney Transplant Recipients

Intervention

Drug:
• Tacrolimus (CNI) Withdrawal
Recipients of living-donor kidney allografts are given induction therapy with rabbit antithymocyte globulin (RATG, Thymoglobulin®) and treated with a regimen of mycophenolate mofetil (MMF), prednisone and tacrolimus. Subjects without any clinical acute rejection (AR) in the first 6 months, without borderline or acute rejection on the 6 month biopsy, and without donor-specific antibody (DSA) at anytime, including the 6 month test will be randomized (2:1) to tacrolimus (CNI) withdrawal.
• Standard Immunosuppressive Therapy
Recipients of living-donor kidney allografts are given induction therapy with rabbit antithymocyte globulin (RATG, Thymoglobulin®) and treated with a regimen of mycophenolate mofetil (MMF), prednisone and tacrolimus.

Locations

Country	Name	City	State
Canada	Toronto General Hospital	Toronto	Ontario
Canada	Health Sciences Centre	Winnipeg	Manitoba
United States	University of Michigan Hospital	Ann arbor	Michigan
United States	Brigham & Women's Hospital	Boston	Massachusetts
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	University Hospitals of Cleveland	Cleveland	Ohio
United States	The Methodist Hospital	Houston	Texas
United States	University of California Los Angeles	Los Angeles	California
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Mount Sinai School of Medicine	New York	New York
United States	Washington University	St. Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Clinical Trials in Organ Transplantation

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

Hricik DE, Formica RN, Nickerson P, Rush D, Fairchild RL, Poggio ED, Gibson IW, Wiebe C, Tinckam K, Bunnapradist S, Samaniego-Picota M, Brennan DC, Schröppel B, Gaber O, Armstrong B, Ikle D, Diop H, Bridges ND, Heeger PS; Clinical Trials in Organ Transpla — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants with Incremental IF/A scores >2 at 18 Months Post-Randomization		IF/TA scores on protocol biopsies obtained at 18 months postrandomization will be compared to those obtained at the time of implantation for this measurement.	Yes
Secondary	Estimated GFR Using the Chronic Kidney Disease Epidemiology (CKD-EPI) Equation		6 to 18 months post-randomization	Yes
Secondary	Incidence of Acute Rejection		6 to 18 months post-randomization	Yes
Secondary	Allograft Survival Rate		6 to 18 months post-randomization	Yes
Secondary	Participant Survival Rate		6 to 18 months post-transplantation	Yes
Secondary	Percentage of Participants with New Donor Specific Antibodies (DSAs)		6 to 18 months post-randomization	Yes
Secondary	Percentage of Participants with Donor-Specific Memory Using Elispot		6 to 18 months post-randomization	Yes
Secondary	Percentage of Participants in the Experimental Arm Off Tacrolimus		6 to 18 months post-randomization	Yes
Secondary	Incremental Change in IF/TA Scores		6 to 18 months post-transplant	Yes
Secondary	Measurement of Urinary Parameters Before and After Randomization	Urinary chemokines and gene expression)	6 months post-transplant to 18 months post-randomization	Yes

External Links

•   Clinical Trials in Organ Transplantation (CTOT)
•   National Institute of Allergy and Infectious Diseases (NIAID)