Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT01208337 |
| Other study ID # |
IRB0701088 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
April 2007 |
| Est. completion date |
November 2014 |
Study information
| Verified date |
March 2023 |
| Source |
University of Pittsburgh |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
This open-label clinical trial will evaluate the safety and efficacy of Alemtuzumab (Campath,
Bayer Corp., Pittsburgh) in children (0-17) and adults (18-25) receiving intestinal
transplant. Seventy-five subjects receiving primary or repeat intestine transplantation will
be enrolled. Primary endpoints include the incidence and severity of biopsy-proven acute
cellular rejection, the incidence of freedom from steroids at 5 years, and the incidence of
subjects with steroid-free Tacrolimus at whole blood concentrations < 10 ng/ml. Secondary
endpoints include a) incidence and severity of opportunistic infections (CMV and EBV),
post-transplant lymphoproliferative disorder (PTLD), and chronic rejection b) use of
non-immunosuppressive co-medications, c) time to repopulation of all lymphocyte subsets, d)
longitudinal characterization of donor-specific alloreactivity in mixed lymphocyte responses
(MLR), to identify the time at which it decreases to a level less than third-party-specific
alloreactivity e) longitudinal expression (mRNA) of genes, to identify rejection- and
non-rejection-specific genes and f) characterization of whole genome mutations, which show
differences in parent-to-child transmission between rejectors and non-rejectors. This will
identify rejection- and non-rejection-specific genes bearing genetic variants, which might
impact on gene function, and complement candidate gene identification efforts based on SNP
transmission.
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.
1. Premedication with acetaminophen 10 mg/kg orally + diphenhydramine 1 mg/kg intravenously
+ methylprednisolone 2 mg/kg, intravenously will occur 30 minutes before Alemtuzumab
administration.
2. 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.
3. 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:
1. 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
2. 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.
3. 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.
4. 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.
