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HLA-Identical Sibling Renal Transplant Tolerance With Donor Hematopoietic Stem Cells and Campath-1H

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City:   Chicago
State:   Illinois
Zip Code:   60611
Conditions:   Immunosuppression - Kidney Transplantation - Graft Rejection
Purpose:   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.
Study Summary:   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 unresponsiveness. 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 CD34+ stem cells (DHSC).
Criteria:   Inclusion Criteria: - Patient fully informed, signed dated 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%) 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. Exclusion Criteria: - Patient previously received/receiving transplant other than kidney. - Patient receiving ABO 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 AST (SGOT) and/or 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 therapy. - History of ITP or TTP
NCT ID:   NCT00619528
Primary Contact:   Principal Investigator
Joshua Miller, MD
Northwestern University

Joshua Miller, MD
Phone: (312) 503-1801
Email: joshuamiller@northwestern.edu
Backup Contact:   N/A
Location Contact:   Chicago, Illinois 60611
United States

jane l charette, RN, RN, BSN, CCRC
Phone: 312-694-0238
Email: jane-charette@northwestern.edu

Site Status: Recruiting

Data Source:   ClinicalTrials.gov
Date Processed:   May 22, 2013
Modifications to this listing:   Only selected fields are shown, please use the link below to view all information about this clinical trial.
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