Clinical trial NCT01517984: Immune Monitoring and CNI Withdrawal in Low Risk Recipients of Kidney Transplantation
Official title: Immune Monitoring and Calcineurin Inhibitor (CNI) Withdrawal in Low Risk Recipients of Kidney Transplantation
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Kidney Transplant Recipients
Keywords: recipients of living-donor kidney allografts
antithymocyte globulin (ATG) induction
calcineurin inhibitors (CNIs)
CNI withdrawal
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Clinical Trials in Organ Transplantation
First posted: 2012-01-25
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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transplanted kidneys work and the response of people's immune systems as tacrolimus, a calcineurin inhibitor (CNI), is withdrawn.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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With Incremental IF/A Scores >2 at 24 Months Post-Randomization
timeFrame: IF/TA scores on protocol biopsies obtained at 24 months post-randomization will be compared to those obtained at the time of implantation for this measurement.
Secondary outcomes:
measure: Estimated GFR Using the Chronic Kidney Disease Epidemiology (CKD-EPI) Equation
timeFrame: 6 months post-transplantation, 24 months post-transplantation
measure: Incidence of Acute Rejection
timeFrame: 6 to 18 months post-randomization
measure: Allograft Survival Rate
timeFrame: 6 to 18 months post-randomization
measure: Participant Survival Rate
timeFrame: 6 to 18 months post-transplantation
measure: Percentage of Participants With New Donor Specific Antibodies (DSAs)
timeFrame: 6 to 18 months post-randomization
measure: Percentage of Participants With Donor-Specific Memory Using Elispot
timeFrame: 6 to 18 months post-randomization
measure: Percentage of Participants in the Experimental Arm Off Tacrolimus
timeFrame: 18 months post-randomization
measure: Incremental Change in IF/TA Scores
timeFrame: 6 to 18 months post-transplant
measure: Measurement of Urinary Parameters Before and After Randomization
timeFrame: 6 months post-transplantation to 18 months post-randomization
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Hospital
state: Michigan
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Cleveland
country: United States
facility: University Hospitals of Cleveland
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Houston
country: United States
facility: The Methodist Hospital
state: Texas
city: Winnipeg
country: Canada
facility: Health Sciences Centre
state: Manitoba
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
Study officials:
affiliation: University Hospitals Cleveland Medical Center
name: Donald Hricik, MD
role: STUDY_CHAIR
affiliation: Icahn School of Medicine at Mount Sinai
name: Peter S. Heeger, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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, Schroppel B, Gaber O, Armstrong B, Ikle D, Diop H, Bridges ND, Heeger PS; Clinical Trials in Organ Transplantation-09 Consortium. Adverse Outcomes of Tacrolimus Withdrawal in Immune-Quiescent Kidney Transplant Recipients. J Am Soc Nephrol. 2015 Dec;26(12):3114-22. doi: 10.1681/ASN.2014121234. Epub 2015 Apr 29.