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

NCT ID: NCT01517984

Last Updated: 2017-09-11

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-11-30
• Study Completion Date: 2015-05-31

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transplanted kidneys work and the response of people's immune systems as tacrolimus, a calcineurin inhibitor (CNI), is withdrawn.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

Conditions

Kidney Transplant Recipients

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tacrolimus (CNI) Withdrawal

Subjects randomized (2:1) to tacrolimus (CNI) withdrawal.

Recipients of living-donor kidney allografts are given induction therapy with rabbit antithymocyte globulin (RATG, Thymoglobulin®) and treated with a standard immunosuppressive 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 are randomized (2:1) to tacrolimus (CNI) withdrawal.

Group Type: EXPERIMENTAL

Tacrolimus (CNI) Withdrawal

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Standard Immunosuppressive Therapy

Subjects randomized to standard immunosuppressive therapy, without subsequent tacrolimus (CNI) withdrawal.

Recipients of living-donor kidney allografts are given induction therapy with rabbit antithymocyte globulin (RATG, Thymoglobulin®) and treated with a standard immunosuppressive regimen of mycophenolate mofetil (MMF), prednisone and tacrolimus. Tacrolimus (CNI) withdrawal does not occur.

Group Type: ACTIVE_COMPARATOR

Standard Immunosuppressive Therapy

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Other Intervention Names

ATG Induction,Tacrolimus (CNI), MMF and Prednisone, Followed by CNI Withdrawal; rabbit antithymocyte globulin (RATG); Thymoglobulin®; calcineurin inhibitor (CNI); mycophenolate mofetil; CellCept®; ATG induction,Tacrolimus (CNI), MMF and Prednisone; rabbit antithymocyte globulin (RATG); Thymoglobulin®; calcineurin inhibitor (CNI); mycophenolate mofetil; CellCept®

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.

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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Clinical Trials in Organ Transplantation

NETWORK

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Donald Hricik, MD

Role: STUDY_CHAIR

University Hospitals Cleveland Medical Center

Peter S. Heeger, MD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Locations

University of California Los Angeles

Los Angeles, California, United States

Yale University School of Medicine

New Haven, Connecticut, United States

Brigham & Women's Hospital

Boston, Massachusetts, United States

University of Michigan Hospital

Ann Arbor, Michigan, United States

Washington University

St Louis, Missouri, United States

Mount Sinai School of Medicine

New York, New York, United States

University Hospitals of Cleveland

Cleveland, Ohio, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

The Methodist Hospital

Houston, Texas, United States

Health Sciences Centre

Winnipeg, Manitoba, Canada

Toronto General Hospital

Toronto, Ontario, Canada

Countries

United States; Canada

References

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.

Reference Type: RESULT

PMID: 25925687 (View on PubMed)

Related Links

https://www.niaid.nih.gov/

National Institute of Allergy and Infectious Diseases (NIAID)

https://www.ctotstudies.org/

Clinical Trials in Organ Transplantation (CTOT)

Other Identifiers

DAIT CTOT-09

Identifier Type: -

Identifier Source: org_study_id