- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01208337
Safety and Efficacy of Alemtuzumab in Pediatric Intestinal Transplantation
Pharmacodynamics, Pharmacogenomics, and Preliminary Safety and Efficacy of Alemtuzumab Induction and Tacrolimus in Pediatric Intestinal Transplantation (IND # 100496)
Study Overview
Status
Intervention / Treatment
Detailed Description
Intraoperatively, it is our impression that Alemtuzumab may predispose to mild coagulopathy. Therefore, we have elected to administer steroids, and withhold Alemtuzumab in the operating room for all small bowel transplant recipients.
- Premedication with acetaminophen 10 mg/kg orally + diphenhydramine 1 mg/kg intravenously + methylprednisolone 2 mg/kg, intravenously will occur 30 minutes before Alemtuzumab administration.
Steroids up to 10 mg/kg as bolus will be administered intravenously in the operating room prior to reperfusion of the allograft followed by decreasing amounts of low-dose steroids post-transplant.
Day 1 post-transplant: up to 5 mg/kg can be given Day 2 post-transplant: up to 4 mg/kg can be given Day 3 post-transplant: up to 3 mg/kg can be given Day 4 post-transplant: up to 2 mg/kg can be given Day 5 post-transplant: up to 1 mg/kg can be given
Maintenance steroids are tapered thereafter by switching to equivalent amounts of oral prednisone, as soon as ileus results and oral intake intake is possible. By the end of the first month, all patients receive no more than 2.5-5 mg/day of prednisone. This amount is exceeded only if rejection occurs. Long-term prednisone usage may be elected in patients re-transplanted for chronic rejection.
- A single dose of Alemtuzumab 0.4-0.5 mg/kg will be given intravenously slowly post-operatively. Total dose will not exceed 30 mg.
Procedures:
Tacrolimus will be initiated at 0.01 mg per kg body weight orally. If biopsy-proven rejection does not occur, Tacrolimus will be titrated to whole blood concentrations:
Month 1: 15-20 ng/ml Months 2-3: 10-15 ng/ml Month 4-6: 8-10 ng/ml Months 6-12: 5-10 ng/ml
- This minimization protocol will be delayed by 3 months if biopsy proven acute cellular rejection occurs. At the event of rejection, Tacrolimus minimization and steroids sparing will be discontinued and standard immunosuppression will be instituted. For example, if rejection occurs, Tacrolimus is increased to month 1 levels of 15-20 ng/ml, and steroids added to the regimen. Steroids will be reduced or eliminated within 3 months of rejection, and tacrolimus minimization resumed as described above. These levels of Tacrolimus are our standards of care in the event of rejection. Current immunosuppressive protocols at our center include rabbit anti-human thymocyte globulin (rATG) with Tacrolimus monotherapy, or Tacrolimus + steroid without induction.
- Laboratory tests per clinical protocol. The clinical standard of care will be followed in performing post-Tx monitoring labs consisting of complete blood count with differential count, serum sodium, potassium, chloride, bicarbonate, BUN, creatinine and glucose, and liver function tests consisting of Total bilirubin, aspartate alanine transaminase (ALT), aspartate glutamine transaminase (AST), and glutamyl galactosyl transaminase (GGT), and TAC whole blood concentrations. These laboratory tests are performed at least weekly in the first and second months, twice monthly in month 3, and monthly thereafter to the sixth month. The extra 1 to 11 ml needed for pharmacodynamic and pharmacogenomic studies is discussed further in items 5 and in Table 1.
- Surveillance intestinal allograft biopsies will be performed per clinical surveillance protocol-twice weekly in the first month, weekly in the second month, two-weekly in the third month, and at least monthly thereafter until the end of the 6th month, and at least annually thereafter. Surveillance biopsies are done because no blood test exists to indicate intestinal allograft dysfunction.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age 0-25 years
- male and female
- Primary intestine transplantation, repeat intestine transplantation, and intestine transplantation in the setting of a previous or simultaneous liver transplantation
Exclusion Criteria:
- documented non-compliance
- known hypersensitivity to egg protein
- pregnancy
- malignancy
- hepatitis C and B defined as anti-HCV antibody positive, and anti-Hepatitis B surface antigen or Hepatitis B core antibody positive or HBV DNA positive.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: Alemtuzumab induction
Intestine transplant recipients who receive induction with alemtuzumab prior to transplantation.
|
Alemtuzumab is a monoclonal antibody directed against the CD52 antigen.
A single dose of 0.3-0.4
mg/kg is given to enrolled subjects at the time of intestine transplantation, 30 minutes after premedication with acetaminophen, diphenhydramine and methylprednisolone
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of Post Transplant Lymphoproliferative Disorder (PTLD)
Time Frame: 5 Year
|
Asses safety of Alemtuzumab in combination with Tacrolimus and steroids in twenty-three pediatric intestine allograft recipients by calculating the rate in which PTLD occurred amongst the study population.
|
5 Year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of Biopsy-proven Acute Cellular Rejection
Time Frame: 1 Year
|
Biopsy-proven incidence of acute cellular rejection
|
1 Year
|
Incidence of Patients in Whom Steroids Are Not Used
Time Frame: 1 year
|
As part of analysis for assessing effectiveness and safety of Alemtuzumab Induction at the time of transplant, it is important to assess the incidence in which patients enrolled were able to wean off of steroids post-transplant compared to historical controls.
|
1 year
|
Incidence of Patients in Whom Tacrolimus Whole Blood Concentration Less Than 10 ng/ml Are Being Used at 1-year Follow-up.
Time Frame: 1 year
|
Tacrolimus whole blood concentrations less than 10 ng/ml
|
1 year
|
Incidence of Patients in Whom Steroids Are Not Used
Time Frame: 5 year
|
As part of analysis for assessing effectiveness and safety of Alemtuzumab Induction at the time of transplant, it is important to assess the incidence in which patients enrolled were able to wean off of steroids post-transplant compared to historical controls.
|
5 year
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Rakesh Sindhi, MD, Children's Hospital of Pittsburgh of UPMC/University of Pittsburgh
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- IRB0701088
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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