Combination Immunosuppressive Therapy to Prevent Kidney Transplant Rejection in Adults

NCT00078559 | Completed Phase 1 Results DMC

• 2 other identifiers: DAIT ITN013STH-2003-0435
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Kidney Transplantation; Kidney Disease

Keywords

Immunosuppression; Renal Failure

Outcome Measures

Primary Outcomes (1)

• Number of Acute Rejections in All Enrolled Participants

  Number of acute rejections\[1\] in all enrolled subjects from the time of transplantation to the end of the trial (four years post-transplant) 1. Acute rejection is defined as a biopsy-proven rejection: a renal biopsy demonstrates acute cellular or humoral rejection of Banff\[2\] Grade 1B or greater; or presumed rejection in the absence of biopsy-proven rejection, the participant is treated for an unexplained 20% increase in serum creatinine. 2. Reference: Racusen LC, Solez K, Colvin RB et al,The Banff 97 working classification of renal allograft pathology. Kidney Int,55: 713-723, 1999

  Four years post-transplant

Secondary Outcomes (13)

• Number of Acute Rejections in All Enrolled Participants Following Sirolimus Withdrawal

  Transplantation to end of study (up to four years post-transplant)

• Number of Acute Rejections Between Initiation of Sirolimus Withdrawal and End of Study

  Initiation of sirolimus to end of study (up to four years post-transplant)

• Time From Transplantation to Acute Rejection in Participants for Whom Sirolimus Withdrawal Was Not Initiated

  Transplantation to acute rejection (up to four years post-transplantation)

• Time From Transplantation to Acute Rejection in Participants for Whom Acute Rejection Occurred During the 1 Year Post-transplant Period

  Transplantation to acute rejection (up to one year post-transplant)

• Number of Deaths Stratified by Sirolimus Withdrawal Status

  Transplantation to Death (up to four years post-transplant)

Study Arms (1)

Alemtuzumab

EXPERIMENTAL

Drug: Alemtuzumab; Drug: Sirolimus; Drug: Tacrolimus; Procedure: Kidney transplant; Drug: Methylprednisolone (or equivalent); Drug: Acetaminophen; Drug: Diphenhydramine; Drug: Trimethoprim (TMP)/Sulfa (Bactrim, Septra); Drug: Valgancyclovir; Drug: Acyclovir; Drug: Pentamidine; Drug: Clotrimazole; Drug: Nystatin

Interventions

Alemtuzumab DRUG

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

Alemtuzumab

Sirolimus DRUG

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

Alemtuzumab

Tacrolimus DRUG

2mg orally twice daily, on days 1-60

Alemtuzumab

Kidney transplant PROCEDURE

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

Alemtuzumab

Methylprednisolone (or equivalent) DRUG

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

Alemtuzumab

Acetaminophen 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

Alemtuzumab

Diphenhydramine 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

Alemtuzumab

Trimethoprim (TMP)/Sulfa (Bactrim, Septra) DRUG

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

Alemtuzumab

Valgancyclovir 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

Alemtuzumab

Acyclovir 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.

Alemtuzumab

Pentamidine 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

Alemtuzumab

Clotrimazole DRUG

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

Alemtuzumab

Nystatin 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)

Alemtuzumab

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• Immune Tolerance Network (ITN): collaborator

Study Sites (1)

University of Wisconsin - Department of Medicine

Madison, Wisconsin, 53792-1735, United States

Location

Related Publications (3)

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

  PMID: 15599882 BACKGROUND

• 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.

  PMID: 12079485 BACKGROUND

• 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.

  PMID: 15888040 BACKGROUND

Related Links

• Click here for the Immune Tolerance Network Web site
• Related Info

MeSH Terms

Conditions

Kidney Diseases; Renal Insufficiency

Interventions

Alemtuzumab; Sirolimus; Tacrolimus; Kidney Transplantation; Methylprednisolone; Acetaminophen; Diphenhydramine; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Acyclovir; Pentamidine; Clotrimazole; Nystatin

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Macrolides; Lactones; Organic Chemicals; Renal Replacement Therapy; Therapeutics; Organ Transplantation; Transplantation; Surgical Procedures, Operative; Urologic Surgical Procedures; Urogenital Surgical Procedures; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Acetanilides; Anilides; Amides; Aniline Compounds; Amines; Ethylamines; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Sulfamethoxazole; Benzenesulfonamides; Sulfonamides; Sulfanilamides; Sulfones; Sulfur Compounds; Drug Combinations; Pharmaceutical Preparations; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Benzamidines; Amidines; Imidazoles; Azoles

Limitations and Caveats

The absence of a control group in this pilot trial precludes any comparison between alemtuzumab-induced patients with further minimization and patients with more conventional immunosuppressive approaches, and is a limitation of the current study

Results Point of Contact

• Title: Arjang Djamali, MD, MS, FASN
• Organization: University of Wisconsin - Department of Medicine, Madison, Wisconsin

axd@medicine.wisc.edu

608-262-7330

Study Officials

• A. D'jamali, MD, MS

  Immune Tolerance Network (ITN)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2004
• First Posted: March 2, 2004
• Study Start: November 1, 2003
• Primary Completion: February 1, 2010
• Study Completion: February 1, 2010
• Last Updated: June 29, 2018
• Results First Posted: July 9, 2012

Record last verified: 2018-05

Locations

US (1)