The purpose of this study is to attempt to eliminate the necessity of immunosuppressive
therapy for HLA-identical sibling Kidney Transplants, examine cellular chimerism of donor
hematopoietic stem cell (DHSC) lineages for pairs to demonstrate immunologic
unresponsiveness, and to investigate the safety and efficacy of the treatment regimen
including withdrawal of immunosuppression after one year post-transplant for those
recipients having received DHSC infusions.
Primary Study Objectives:
1. To remove all immunosuppressive therapy from recipients of HLA-identical sibling renal
transplants within 24 months of transplantation.
2. To detect and follow cellular (macro) chimerism of donor hematopoietic stem cell (DHSC)
lineages and the generation of T-regulatory cells using specialized immunomonitoring
assays for these donor/recipient pairs to demonstrate specific immunologic
3. To investigate the safety and efficacy of a treatment regimen consisting of induction
therapy with Campath-1H and steroid-free low dose maintenance immunosuppression,
consisting of mycophenolate mofetil (MMF) and tacrolimus converted to sirolimus. This
is to be followed by complete withdrawal of immunosuppression beginning at one year, at
a minimum, post transplant, in recipients who have also been given four infusions of
purified donor hematopoietic Cluster of Differentiation (CD)34+ stem cells (DHSC).
- Patient fully informed, signed dated Institutional Review Board (IRB)-approved
informed consent form obtained directly by the P.I., Co-P.I., or Res. Nurse, and
willing to follow study procedures for the duration of study (3 yrs).
- Recipient: a hematocrit of ≥ 33%, and a hemoglobin of ≥ 11.0 g/dL.
- Weight > 40 kg.
- Primary renal allograft: living related (HLA-identical donor-recipient sibling pairs)
- Negative B-cell and T-cell cytotoxic cross-match, and a low (≤ 10%) Panel Reactive
Antibody (PRA) using cytotoxicity.
- Women of childbearing potential: negative qualitative serum pregnancy test.
- Patients studied equivalently as available for transplant using criteria, w/out
regard to gender, race, or ethnicity.
- Normal echocardiogram w/ ejection fraction >50%.
- Male participants w/ reproductive potential agree to use approved methods of birth
control during treatment w/ Campath-1H and for minimum of 6 months following last
dose. Female participants of childbearing potential agree to use approved methods of
birth control for duration of participation in study.
- Patient agrees to follow-up every 2 months after year 3, up to 10 years.
- Patient previously received/receiving transplant other than kidney.
- Patient receiving ABO (blood type) incompatible donor kidney.
- Recipient/donor is ELISA positive for human immunodeficiency virus (HIV), antibody
positive for hep. C, or surface antigen positive for hep. B.
- Patient has current malignancy or history of malignancy (within past 5 years), except
non-metastatic basal or squa¬mous cell carcinoma of the skin, or carcinoma in situ of
the cervix that has been treated successfully.
- Patients w/ significant liver disease, defined as having during past 28 days
continuously elevated aspartate aminotransferase (AST (SGOT)) and/or Alanine
Aminotransferase (ALT (SGPT)) levels greater than 3 times the upper value of the
normal range at this center.
- Patient has uncontrolled concomitant infections and/or severe diarrhea, vomiting,
active upper gastro-intestinal tract malabsorption or active peptic ulcer or other
unstable medical condition that could interfere w/ study objectives.
- Patient currently receiving investigational drug or received an investigational drug
within 30 days pre-transplant.
- Patient currently receiving immunosuppressive agent.
- In investigator's judgment, anticipated that patient unable to take medications
orally or via nasogastric tube by morning of second day (i.e., skin closure).
- Concurrent use of warfarin, fluvastatin, astemizole, pimozide, cisapride,
terfenadine, or ketoconazole.
- Patient hypersensitivity to tacrolimus, Campath-1H, Thymoglobulin, daclizumab
(Zenapax®), sirolimus, MMF or corticosteroids.
- Patient pregnant or lactating.
- Patients w/ screening/baseline total white blood cell count <4000/mm3; platelet count
<100,000/mm3; fasting triglycerides >400 mg/dl (>4.6 mmol/L); fasting total
cholesterol >300 mg/dl (>7.8 mmol/L); fasting HDL-cholesterol <30 mg/dl; fasting
LDL-cholesterol >200 mg/dl.
- Patient unlikely to comply w/ visits.
- Patient w/ any form of substance abuse, psychiatric disorder or condition that, in
investigator's opinion, may invalidate communication.
- Expected that tacrolimus cannot be instituted for over 5 days post-operatively.
- Patients w/ cytotoxic PRA value >10% any time pre-enrollment.
- Patients w/ Graves disease, unless previously treated w/ radioiodine ablative
- History of idiopathic thrombocytopenic purpura (ITP) or thrombotic thrombocytopenic