Combination Immunosuppressive Therapy to Prevent Kidney Transplant Rejection in Adults

NCT ID: NCT00078559

Last Updated: 2018-06-29

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2003-11-30

Study Completion Date

2010-02-28

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Transplant rejection occurs when a patient's body does not recognize the new organ and attacks it. Patients who have kidney transplants must take drugs to prevent transplant rejection. Alemtuzumab is a man-made antibody used to treat certain blood disorders. The purpose of this study is to test the safety and effectiveness of using alemtuzumab in combination with two other drugs, sirolimus and tacrolimus, to prevent organ rejection after kidney transplantation. This study will also test whether this combination of medications will allow patients to eventually stop taking antirejection medications entirely.

Study hypothesis: A new strategy of immunosuppression using alemtuzumab, tacrolimus, and sirolimus for human renal transplantation will permit a step-wise withdrawal from immunosuppressive drugs.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Drugs that suppress the immune system, such as sirolimus and tacrolimus, have contributed to increased success of transplantation. However, to prevent organ rejection, transplant recipients need to take immunosuppressive drugs for the rest of their lives, and these drugs make patients more susceptible to infection, endangering their health and survival. Regimens that are less toxic to or can eventually be withdrawn from transplant recipients are needed. Alemtuzumab is a monoclonal antibody that binds to and depletes excess T cells in the bone marrow of leukemia patients. This study will determine the effects of intravenous alemtuzumab and oral sirolimus and tacrolimus after kidney transplantation. The study will also evaluate this regimen's potential to allow eventual discontinuation of components of long-term immunosuppressive therapy.

This study will last up to 4 years. Participants will undergo kidney transplantation on Day 0 and will receive intravenous doses of alemtuzumab, acetaminophen, and diphenhydramine on Days 0, 1, and 2, as well as methylprednisolone on Day 0. After transplant, patients will receive up to 10 days of valganciclovir or acyclovir. Participants will take tacrolimus daily by mouth for at least 60 days after transplant and sirolimus daily by mouth for at least 12 months after transplant. As part of opportunistic infection (OI) prophylaxis, participants will also take sulfamethoxazole-trimethoprim by mouth 3 times a week, valganciclovir or acyclovir for up to 10 days post-transplant, and clotrimazole or nystatin by mouth for at least 3 months post-transplant.

There will be a minimum of 62 study visits spread out over 4 years after transplant. Vital signs measurement, adverse event and OI reporting, medication history, physical exam, and blood collection will occur at selected visits. Sirolimus withdrawal will begin when a participant meets certain study criteria. The withdrawal process will occur over a minimum of 3 months at an approximate rate of 33% of the pre-withdrawal dose per month. Participants eligible for sirolimus withdrawal will undergo several kidney biopsies, including one 2 weeks prior to the start of withdrawal, 6 and 12 months after completion of withdrawal, 1 year after study enrollment, and annually thereafter.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Kidney Transplantation Kidney Disease

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Alemtuzumab

Group Type EXPERIMENTAL

Alemtuzumab

Intervention Type DRUG

30mg intravenous infusion on days 0 (transplant), 1, and 2

Sirolimus

Intervention Type DRUG

2mg/day orally within 24-48 hrs post-transplant, and adjusted to achieve blood levels of 8-12 ng/mL for 1 year

Tacrolimus

Intervention Type DRUG

2mg orally twice daily, on days 1-60

Kidney transplant

Intervention Type PROCEDURE

Kidney transplant with primary cadaveric or non-HLA-identical living donor kidney (0-3 HLA-antigen mismatch)

Methylprednisolone (or equivalent)

Intervention Type DRUG

250 mg intravenous infusion 60 minutes prior to first dose of alemtuzumab

Acetaminophen

Intervention Type DRUG

650 mg may be given 30-60 minutes prior to start of each infusion of alemtuzumab to prevent infusion related side effects such as fever, skin rash and pruritis

Diphenhydramine

Intervention Type DRUG

25 mg may be given 30-60 minutes prior to start of each infusion of alemtuzumab to prevent infusion related side effects such as fever, skin rash and pruritis

Trimethoprim (TMP)/Sulfa (Bactrim, Septra)

Intervention Type DRUG

1 double strength tablet 3 times a week from day 1 through 1 year post-transplant.

Valgancyclovir

Intervention Type DRUG

Given orally beginning on day 1 for up to 10 days post-transplant (until participant discharged from hospital if prior to 10 days). Dose adjusted based on participants calculated creatinine clearance

Acyclovir

Intervention Type DRUG

400 mg orally twice daily or 800 mg orally four times daily (dose adjusted based on calculated creatinine clearance and cytomegalovirus antibody serologic status of donor and recipient) for a minimum of 3 months starting when valganciclovir discontinued.

Pentamidine

Intervention Type DRUG

300 mg/6 mL inhalation therapy once monthly for a total of 6 treatments. First treatment given within one week post-transplant for participants with a known allergy or intolerance to sulfa

Clotrimazole

Intervention Type DRUG

10 mg orally four times daily for a minimum of 3 months post-transplant (subjects take either clotrimazole or nystatin, not both)

Nystatin

Intervention Type DRUG

500,000 units/5 mL orally four times daily for a minimum of 3 months post-transplant (subjects take either nystatin or clotrimazole, not both)

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Alemtuzumab

30mg intravenous infusion on days 0 (transplant), 1, and 2

Intervention Type DRUG

Sirolimus

2mg/day orally within 24-48 hrs post-transplant, and adjusted to achieve blood levels of 8-12 ng/mL for 1 year

Intervention Type DRUG

Tacrolimus

2mg orally twice daily, on days 1-60

Intervention Type DRUG

Kidney transplant

Kidney transplant with primary cadaveric or non-HLA-identical living donor kidney (0-3 HLA-antigen mismatch)

Intervention Type PROCEDURE

Methylprednisolone (or equivalent)

250 mg intravenous infusion 60 minutes prior to first dose of alemtuzumab

Intervention Type DRUG

Acetaminophen

650 mg may be given 30-60 minutes prior to start of each infusion of alemtuzumab to prevent infusion related side effects such as fever, skin rash and pruritis

Intervention Type DRUG

Diphenhydramine

25 mg may be given 30-60 minutes prior to start of each infusion of alemtuzumab to prevent infusion related side effects such as fever, skin rash and pruritis

Intervention Type DRUG

Trimethoprim (TMP)/Sulfa (Bactrim, Septra)

1 double strength tablet 3 times a week from day 1 through 1 year post-transplant.

Intervention Type DRUG

Valgancyclovir

Given orally beginning on day 1 for up to 10 days post-transplant (until participant discharged from hospital if prior to 10 days). Dose adjusted based on participants calculated creatinine clearance

Intervention Type DRUG

Acyclovir

400 mg orally twice daily or 800 mg orally four times daily (dose adjusted based on calculated creatinine clearance and cytomegalovirus antibody serologic status of donor and recipient) for a minimum of 3 months starting when valganciclovir discontinued.

Intervention Type DRUG

Pentamidine

300 mg/6 mL inhalation therapy once monthly for a total of 6 treatments. First treatment given within one week post-transplant for participants with a known allergy or intolerance to sulfa

Intervention Type DRUG

Clotrimazole

10 mg orally four times daily for a minimum of 3 months post-transplant (subjects take either clotrimazole or nystatin, not both)

Intervention Type DRUG

Nystatin

500,000 units/5 mL orally four times daily for a minimum of 3 months post-transplant (subjects take either nystatin or clotrimazole, not both)

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Kidney transplant with primary cadaveric or non-Human Leukocyte Antigen (HLA)-identical living donor kidney (0-3 HLA-antigen mismatch)
* Receiving only a kidney and no other organs
* Able to take medications by mouth
* Willing to use acceptable methods of contraception

Exclusion Criteria

* Received HLA-identical living-donor kidney transplant
* HLA-antigen mismatch greater than 3
* Panel reactive antibody (PRA) value greater than 10% at any time prior to enrollment
* Received a non-heart-beating donor allograft
* Received a kidney from a donor who is greater than 60 years of age
* End-stage Renal Disease (ESRD) due to Focal Segmental Glomulerosclerosis (FSGS)
* Previous kidney transplant
* Received multiorgan transplant
* Concomitant systemic corticosteroid therapy for other medical diseases
* Known hypersensitivity to alemtuzumab, tacrolimus, methylprednisolone, or sirolimus
* Human Immunodeficiency Virus (HIV) infected
* Hepatitis C virus infected
* Positive for hepatitis B surface antigen
* Received dual or en-bloc pediatric kidneys
* Anti-human Globulin (AHG) or T cell crossmatch positive
* Investigational drug within 6 weeks of study entry
* Known clinically significant cardiovascular or cerebrovascular disease
* Previous or current history of cancer or lymphoma. Patients with adequately treated basal or squamous cell skin carcinoma are not excluded.
* Clinically significant coagulopathy or a requirement for chronic anti-coagulation therapy precluding biopsy
* Cytomegalovirus (CMV)-negative recipient, if received kidney is from a CMV-positive donor
* History of a psychological illness or condition that, in the opinion of the investigator, may interfere with the study
* Graves disease. Patients who have been previously adequately treated with radioiodine ablative therapy are not excluded.
* Active systemic infections
* Platelets less than 100,000 cells/mm\^3 at study entry
* Pregnant or breastfeeding
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Immune Tolerance Network (ITN)

NETWORK

Sponsor Role collaborator

University of Wisconsin, Madison

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

A. D'jamali, MD, MS

Role: PRINCIPAL_INVESTIGATOR

Immune Tolerance Network (ITN)

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

University of Wisconsin - Department of Medicine

Madison, Wisconsin, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

First MR. Tacrolimus based immunosuppression. J Nephrol. 2004 Nov-Dec;17 Suppl 8:S25-31.

Reference Type BACKGROUND
PMID: 15599882 (View on PubMed)

Gourishankar S, Turner P, Halloran P. New developments in immunosuppressive therapy in renal transplantation. Expert Opin Biol Ther. 2002 Jun;2(5):483-501. doi: 10.1517/14712598.2.5.483.

Reference Type BACKGROUND
PMID: 12079485 (View on PubMed)

Watson CJ, Bradley JA, Friend PJ, Firth J, Taylor CJ, Bradley JR, Smith KG, Thiru S, Jamieson NV, Hale G, Waldmann H, Calne R. Alemtuzumab (CAMPATH 1H) induction therapy in cadaveric kidney transplantation--efficacy and safety at five years. Am J Transplant. 2005 Jun;5(6):1347-53. doi: 10.1111/j.1600-6143.2005.00822.x.

Reference Type BACKGROUND
PMID: 15888040 (View on PubMed)

Related Links

Access external resources that provide additional context or updates about the study.

http://www.immunetolerance.org

Click here for the Immune Tolerance Network Web site

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

H-2003-0435

Identifier Type: OTHER

Identifier Source: secondary_id

DAIT ITN013ST

Identifier Type: -

Identifier Source: org_study_id

NCT00585130

Identifier Type: -

Identifier Source: nct_alias

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Tolerance by Engaging Antigen During Cellular Homeostasis
NCT03504241 ACTIVE_NOT_RECRUITING PHASE1