Study of Alemtuzumab Versus Anti-thymocyte Globulin to Help Prevent Rejection in Kidney and Pancreas Transplantation

NCT00331162 | Completed Phase 4 Results FDA Drug

• 1 other identifier: BG04-498
• Study Type: interventional
• Target: 222
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to compare the effects of the two most commonly used anti-T cell induction agents(alemtuzumab and rabbit anti-thymocyte globulin) to prevent rejection in kidney and pancreas transplant patients. Alemtuzumab is Food and Drug Administration (FDA) approved for treating a certain type of cancer (leukemia), and Thymoglobulin® (rabbit anti-thymocyte globulin) is approved for anti-rejection treatment, but neither drug is FDA approved for administration at the time of transplantation to help prevent rejection. Even so, many transplant centers use these medications at the time of transplantation and believe that their use helps to decrease the risk of developing rejection following kidney and pancreas transplantation. Which drug might be better is not known. Subjects will receive either alemtuzumab (one administration) or rabbit anti-thymocyte (3 to 7 doses) at and within the first week of transplantation. Subjects will be assigned to either the alemtuzumab or rabbit anti-thymocyte globulin groups by chance. The two groups will be compared to see if there are meaningful differences for survival, organ function, side effects, and quality of life. The follow-up care after transplant for subjects in the study is the same as that for patients who are not in the study, except that a quality of life questionnaire (estimated to take 10 minutes to complete) will be completed at the time of transplant and through year 2 during selected scheduled clinic visits. A retrospective chart review will occur at 3-5 years post-transplant to follow incidence of chronic rejection, patient and graft survival and graft function.

Conditions

Graft Rejection

Keywords

Renal Transplantation; Pancreas Transplantation; Graft Rejection; Immunosuppression; Kidney failure, chronic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (3)

• Patient Survival

  The number of patients that survived after transplantation occurred was reported.

  5 years

• Graft Survival

  The number of patients with graft survival after kidney alone, simultaneous pancreas-kidney (SPK), and pancreas after kidney (PAK) transplant.

  5 years

• Acute Rejection

  The number of patients with acute rejection after transplantation was reported.

  5 years

Secondary Outcomes (5)

• Hematologic Adverse Events

  2 years

• Infectious Adverse Events

  2 years

• Other Adverse Events

  2 years

• Cost

  2 years

• Health Status and Quality of Life

  2 years

Study Arms (2)

1

ACTIVE COMPARATOR

Alemtuzumab

Drug: Alemtuzumab

2

ACTIVE COMPARATOR

Anti-Thymocyte Globulin

Drug: Anti-Thymocyte Globulin

Interventions

Alemtuzumab DRUG

30 mg/100ml NS intraoperatively. Start after dexamethasone administration and prior to reperfusion of the allograft. Infuse over a minimum of 2 hours.

1

Anti-Thymocyte Globulin DRUG

1.5 mg/kg per dose through a central line intraoperatively and on POD# 2 and 4, then continue on alternate days until a therapeutic tacrolimus(or cyclosporine) level is achieved, or until the SCr \< 3-4 mg/dL. Give first dose over 6 hours, subsequent doses over 4 hours. Premedication to be given with the first 3 doses: Tylenol 650mg PO/PR Benadryl 25-50mg PO/IV Daily scheduled corticosteroid dose or other corticosteroid as deemed appropriate. Hold infusion if temperature \> 100.5ºF; Adjust dose for low WBC or Plt count Peripheral Thymoglobulin administration: Prepare dose in 500cc NS; Add heparin 1,000 units and hydrocortisone 20mg to the bag; Infuse over a minimum of 6 hours

2

Eligibility Criteria

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

You may qualify if:

• Male or female patients who receive a simultaneous pancreas and kidney transplant, pancreas after kidney transplant, or solitary pancreas transplant
• Age 18 to 65
• Females of child bearing potential must have a negative pregnancy test at time of transplant
• Ability to give informed consent

You may not qualify if:

• Inability to give informed consent
• ABO incompatibility
• T-cell or B-cell positive cross match
• Patients with a previous hypersensitivity to alemtuzumab, anti-thymocyte globulin, or any monoclonal or polyclonal antibody preparation
• Current active infection (currently receiving antibiotics, treatment for active infection within 1 week of transplant, or medical judgement)
• Hepatitis B surface antigen positive
• Human immunodeficiency virus positive
• Any malignancy within 2 years except for successfully treated basal or squamous cell carcinoma of skin
• Pregnancy
• Breast feeding women

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead

Study Sites (1)

Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

Related Publications (4)

• Brennan DC, Flavin K, Lowell JA, Howard TK, Shenoy S, Burgess S, Dolan S, Kano JM, Mahon M, Schnitzler MA, Woodward R, Irish W, Singer GG. A randomized, double-blinded comparison of Thymoglobulin versus Atgam for induction immunosuppressive therapy in adult renal transplant recipients. Transplantation. 1999 Apr 15;67(7):1011-8. doi: 10.1097/00007890-199904150-00013.

  PMID: 10221486 BACKGROUND

• Knechtle SJ, Pirsch JD, H Fechner J Jr, Becker BN, Friedl A, Colvin RB, Lebeck LK, Chin LT, Becker YT, Odorico JS, D'Alessandro AM, Kalayoglu M, Hamawy MM, Hu H, Bloom DD, Sollinger HW. Campath-1H induction plus rapamycin monotherapy for renal transplantation: results of a pilot study. Am J Transplant. 2003 Jun;3(6):722-30. doi: 10.1034/j.1600-6143.2003.00120.x.

  PMID: 12780564 BACKGROUND

• Kaufman DB, Leventhal JR, Gallon LG, Parker MA. Alemtuzumab induction and prednisone-free maintenance immunotherapy in simultaneous pancreas-kidney transplantation comparison with rabbit antithymocyte globulin induction - long-term results. Am J Transplant. 2006 Feb;6(2):331-9. doi: 10.1111/j.1600-6143.2005.01166.x.

  PMID: 16426317 BACKGROUND

• Ajmal N, Bogart MC, Khan P, Max-Harry IM, Healy AM, Nunemaker CS. Identifying Promising Immunomodulators for Type 1 Diabetes (T1D) and Islet Transplantation. J Diabetes Res. 2024 Dec 20;2024:5151171. doi: 10.1155/jdr/5151171. eCollection 2024.

  PMID: 39735417 DERIVED

MeSH Terms

Conditions

Kidney Failure, Chronic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2

Interventions

Alemtuzumab; Antilymphocyte Serum

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immune Sera; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Dr. Alan Farney
• Organization: Wake Forest University Health Sciences

afarney@wakehealth.edu

336-716-6510

Study Officials

• Alan C Farney, MD, Ph.D.

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2006
• First Posted: May 29, 2006
• Study Start: February 1, 2005
• Primary Completion: November 28, 2011
• Study Completion: November 28, 2011
• Last Updated: September 6, 2018
• Results First Posted: June 6, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)