Safety in Immunomodulatory Functions of Alemtuzumab (Campath) in Pediatric Kidney Transplantation Recipients

November 15, 2016 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

A Phase II Exploratory Study to Determine the Safety and Study the Immunomodulatory Functions of Induction Therapy With Campath, Combined With Chronic Immunosuppression With Mycophenolate Mofetil and Sirolimus

The purpose of this study is to evaluate the safety of alemtuzumab after kidney transplantation as part of a multitherapy regimen to prevent kidney graft loss and death and to avoid steroids and chronic use of calcineurin inhibitors in pediatric renal transplant recipients 1 to 20 years of age.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Kidney transplantation is widely considered to be the treatment of choice for children with End Stage Renal Disease (ESRD). Improvements in surgical techniques, donor selection, and immunosuppression practices, as well as the enhanced experience of specialized pediatric transplant teams, have all led to marked improvements in patient and kidney graft survival in infants and young children ages 1 to 10. However, young children now have more infections following transplant previously. Also, improved graft survival is not observed in pediatric renal transplant recipients 11 to 17 years of age. Some studies do indicate that the poor long term outcome of patient and kidney survival observed in this age group may be caused by noncompliance with immunosuppressive medications. Therefore, protocols that minimize the use of immunosuppressive medications while retaining kidney function are necessary for improving graft and patient survival in children. This study will evaluate the safety of a regimen containing alemtuzumab after kidney transplantation, followed by steroid avoidance and calcineurin inhibitor withdrawal in pediatric renal transplant recipients 1 to 20 years of age.

The accrual period is scheduled for 18 months. The study follow-up period will last 24 months. All participants enrolled will undergo this treatment schedule: 1.) All participants will receive intravenous alemtuzumab one day before transplantation and 1 day after transplantation. 2.) Mycophenolate mofetil (MMF) will be administered orally no later than 2 days after transplantation. 3.) Participants will begin to take oral tacrolimus twice a day 1 to 3 days after transplantation until Weeks 8 through 12 when 4.) Sirolimus will be initiated. 5.) Sirolimus and MMF will be taken orally until Month 24.

Blood collection will occur at baseline, 1 day before transplant, at Days 1 and 3, at Weeks 2, 4, 6, 8, 10, and at Months 3 through 24. Scheduled kidney (renal) biopsies will be performed at transplant, during Weeks 8 through 12, immediately before conversion to sirolimus, and at Months 6 and 24.

Study Type

Interventional

Enrollment (Actual)

35

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94143-0116
        • University of California, San Francisco
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Children's Hospital, Boston
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital, Philadelphia
    • Washington
      • Seattle, Washington, United States, 98105
        • Children's Hospital and Regional Medical Center, Seattle

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 20 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Between the ages of 1 to 20 (prior to 21st birthday)
  • End Stage Renal Disease
  • Necessity of kidney transplant
  • First kidney transplant received from a living donor
  • A living kidney donor identified
  • No known contraindications to therapy with alemtuzumab
  • Negative pregnancy test before study entry
  • Willing to use approved methods of contraception for the duration of the study, 6 weeks after discontinuation of MMF, and 12 weeks after discontinuation of sirolimus
  • Informed consent from participant, parent, or guardian
  • Current vaccinations, including varicella-zoster (VZV) vaccine, before study enrollment

Exclusion Criteria:

  • Recipient of a deceased donor kidney transplant
  • Multiorgan transplant
  • History of prior organ transplantation
  • Participant sensitized to greater than 0% Panel Reactive Antibody (PRA) within 4 weeks before study enrollment. (If participant receives a blood transfusion status post PRA test, then the PRA must be repeated within 1 week of transplantation)
  • Participants with human leukocyte antigen (HLA) identical living related donors
  • History of primary focal segmented glomerulosclerosis
  • History of other disorders requiring continuous maintenance steroids or calcineurin inhibitors
  • Active systemic infection at time of transplant
  • History of malignancy
  • Infected with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV)
  • Contraindication to receive tacrolimus, sirolimus, MMF, or monoclonal antibody therapy
  • Use of investigational drugs within 4 weeks before study enrollment
  • Recipient of any licensed or investigational live attenuated vaccine(s) within 2 months before study enrollment
  • Family history of high cholesterol

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Alemtuzumab (Campath)
In this open-label, single-arm trial , participants will be administered a 0.3 mg/kg dose of alemtuzumab (Campath) intravenously one day prior to kidney transplantation and one day post kidney transplantation. Participants will then receive a maintenance immunosuppressive regimen of tacrolimus and mycophenolate mofetil (MMF) for 8 to 12 weeks, followed by sirolimus and MMF until 24 months post transplantation.
Drug: Alemtuzumab
Administered intravenously over a period of 2-3 hours. Two doses total, the first will be one day before transplant and the second will be on the day following transplantation. Pre-medication with methylprednisolone, acetaminophen, and Benadryl will be administered before each dose.
Other Names:
  • Campath
  • Campath- 1H
Drug: Tacrolimus
Administered orally at a dose of 0.05-0.1 mg/kg twice daily, beginning 1-3 days following transplantation and continuing until weeks 8-12. Tacrolimus will be discontinued and a treatment regimen with sirolimus will be initiated between weeks 8-12 but some overlap with these medications is possible.
Other Names:
  • Prograf
Drug: Mycophenolate mofetil
Per recommendation
Other Names:
  • CellCept
Drug: Sirolimus
Administered by either liquid or tablet every 12 hours from month 6 until month 24. Dosage will vary throughout the treatment course.
Other Names:
  • Rapamycin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Proportion of Participants With Graft Loss or Death Within 12 Months Post Kidney Transplantation
Time Frame: Up to one year post kidney transplantation procedure
Graft loss is defined as the need for dialysis for more than 30 days duration, allograft nephrectomy, or the decision to withdraw immunosuppression due to graft failure.
Up to one year post kidney transplantation procedure

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

Cooperative Clinical Trials in Pediatric Transplantation

Investigators

  • Study Chair: William Harmon, MD, Boston Children's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2005

Primary Completion (Actual)

November 1, 2009

Study Completion (Actual)

November 1, 2009

Study Registration Dates

First Submitted

October 14, 2005

First Submitted That Met QC Criteria

October 14, 2005

First Posted (Estimate)

October 18, 2005

Study Record Updates

Last Update Posted (Estimate)

January 2, 2017

Last Update Submitted That Met QC Criteria

November 15, 2016

Last Verified

November 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DAIT PC01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Participant level data and additional relevant materials are available to the public in the Immunology Database and Analysis Portal (ImmPort). ImmPort is a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.

Study Data/Documents

  1. Individual Participant Data Set
    Information identifier: SDY134
    Information comments: ImmPort study identifier is SDY134
  2. Study Protocol
    Information identifier: SDY134
    Information comments: ImmPort study identifier is SDY134
  3. Study summary, - schedule of events, -download packages et al.
    Information identifier: SDY134
    Information comments: ImmPort study identifier is SDY134

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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