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

This study has been completed.
Sponsor:
Collaborator:
Cooperative Clinical Trials in Pediatric Transplantation
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00240994
First received: October 14, 2005
Last updated: October 25, 2012
Last verified: September 2012
  Purpose

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.


Condition Intervention Phase
Kidney Failure, Chronic
Kidney Transplantation
Immunosuppression
Drug: Alemtuzumab
Drug: Tacrolimus
Drug: Mycophenolate mofetil
Drug: Sirolimus
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: 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

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 35
Study Start Date: January 2005
Study Completion Date: November 2009
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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. Tacromlimus 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 Name: Prograf
Drug: Mycophenolate mofetil
Per recommendation
Other Name: 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 Name: Rapamycin

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.

  Eligibility

Ages Eligible for Study:   1 Year to 20 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00240994

Locations
United States, California
University of California, San Francisco
San Francisco, California, United States, 94143-0116
United States, Massachusetts
Children's Hospital, Boston
Boston, Massachusetts, United States, 02115
United States, Pennsylvania
Children's Hospital, Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, Washington
Children's Hospital and Regional Medical Center, Seattle
Seattle, Washington, United States, 98105
Sponsors and Collaborators
Cooperative Clinical Trials in Pediatric Transplantation
Investigators
Study Chair: William Harmon, MD Children's Hospital Boston
  More Information

Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00240994     History of Changes
Other Study ID Numbers: DAIT PC01
Study First Received: October 14, 2005
Results First Received: September 13, 2012
Last Updated: October 25, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
End stage renal disease
Kidney transplantation
Renal transplantation
Kidney failure
Pediatric renal transplant recipients
Alemtuzamab
Campath
Mycophenolate mofetil
MMF
CellCept
Tacrolimus
Prograf
Sirolimus
Rapamycin

Additional relevant MeSH terms:
Kidney Failure, Chronic
Renal Insufficiency
Renal Insufficiency, Chronic
Kidney Diseases
Urologic Diseases
Mycophenolate mofetil
Mycophenolic Acid
Sirolimus
Everolimus
Tacrolimus
Alemtuzumab
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Anti-Bacterial Agents
Anti-Infective Agents
Antifungal Agents

ClinicalTrials.gov processed this record on August 20, 2014