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HLA-Identical Sibling Renal Transplant Tolerance

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ClinicalTrials.gov Identifier: NCT00619528
Recruitment Status : Active, not recruiting
First Posted : February 21, 2008
Last Update Posted : May 17, 2019
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Joseph Leventhal, Northwestern University

Tracking Information
First Submitted Date  ICMJE February 8, 2008
First Posted Date  ICMJE February 21, 2008
Last Update Posted Date May 17, 2019
Study Start Date  ICMJE July 2007
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 8, 2008)
  • The ability to withdraw immunosuppression as above 24 months post-transplant with follow-up to 10 years. [ Time Frame: 24 months post-transplant with follow-up to 10 years. ]
  • Patient and graft survival measured at the one-year timepoint post-transplant. [ Time Frame: One Year ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT00619528 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 22, 2013)
  • Patient and graft survival measured at the three year timepoint post-transplant.. [ Time Frame: Three years post-transplant. ]
  • Incidence rate of biopsy-proven acute rejection, defined as a renal biopsy demonstrating acute cellular or humoral rejection of Banff Grade IA or greater. [ Time Frame: Up to 5 years Post-Transplant ]
  • Incidence of chronic allograft nephropathy, determined using renal biopsies and laboratory values, including 24 hour urine protein excretion. [ Time Frame: Up to 5 years post transplant ]
  • Incidence of graft versus host disease (GVHD). [ Time Frame: Up to 5 years Post-Transplant ]
  • Incidence of adverse events associated w/ renal transplantation and immunosuppression, including infections, malignancies, post transplant lymphoproliferative disease (PTLD), thromboembolic events, hyperlipidemia, leukopenia, thrombocytopenia, GI toxic [ Time Frame: Up to 5 years Post-Transplant ]
Original Secondary Outcome Measures  ICMJE
 (submitted: February 8, 2008)
  • Patient and graft survival measured at the three year timepoint post-transplant.. [ Time Frame: Three years post-transplant. ]
  • Incidence rate of biopsy-proven acute rejection, defined as a renal biopsy demonstrating acute cellular or humoral rejection of Banff Grade IA or greater. [ Time Frame: Up to 5 years Post-Transplant ]
  • Incidence of chronic allograft nephropathy, determined using renal biopsies and laboratory values, including 24 hour urine protein excretion. [ Time Frame: Up to 5 years post transplant ]
  • Incidence of graft versus host disease (GVHD). [ Time Frame: Up to 5 years Post-Transplant ]
  • Incidence of adverse events assoc. w/ renal transplantation and immunosuppression, including infections, malignancies, post transplant lymphoproliferative disease (PTLD), thromboembolic events, hyperlipidemia, leukopenia, thrombocytopenia, GI toxic [ Time Frame: Up to 5 years Post-Transplant ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE HLA-Identical Sibling Renal Transplant Tolerance
Official Title  ICMJE HLA-Identical Sibling Renal Transplant Tolerance With Donor Hematopoietic Stem Cells and Campath-1H
Brief Summary 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.
Detailed Description

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 Cluster of Differentiation (CD)34+ stem cells (DHSC).
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Immunosuppression
  • Kidney Transplantation
  • Graft Rejection
Intervention  ICMJE Biological: Infusion of Donor Hematopoietic Stem Cells and Campath-1H
Intervention: a four-dose (peri-operative and 3, 6, and 9-month boost) DHSC infusion protocol using two-dose Campath-1H induction combined with transient (conditioning) Tacrolimus/Sirolimus and MMF therapy will result in a high degree of macro-chimerism (>10%), and a robust prolonged donor-specific (post-thymic) immunoregulatory condition that will allow renal transplant survival in the absence of permanent immunosuppression.
Study Arms  ICMJE Experimental: 1
No separate arms: All Enrolled Receive Same Treatment
Intervention: Biological: Infusion of Donor Hematopoietic Stem Cells and Campath-1H
Publications * Leventhal JR, Mathew JM, Salomon DR, Kurian SM, Friedewald JJ, Gallon L, Konieczna I, Tambur AR, Charette J, Levitsky J, Jie C, Kanwar YS, Abecassis MM, Miller J. Nonchimeric HLA-Identical Renal Transplant Tolerance: Regulatory Immunophenotypic/Genomic Biomarkers. Am J Transplant. 2016 Jan;16(1):221-34. doi: 10.1111/ajt.13416. Epub 2015 Jul 30.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: November 22, 2013)
230
Original Estimated Enrollment  ICMJE
 (submitted: February 8, 2008)
20
Estimated Study Completion Date  ICMJE June 2023
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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 therapy.
  • History of idiopathic thrombocytopenic purpura (ITP) or thrombotic thrombocytopenic purpura (TTP)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00619528
Other Study ID Numbers  ICMJE 2R01DK025243-25A2( U.S. NIH Grant/Contract )
R01DK025243 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Joseph Leventhal, Northwestern University
Study Sponsor  ICMJE Northwestern University
Collaborators  ICMJE National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators  ICMJE
Principal Investigator: Joshua Miller, MD Northwestern University
PRS Account Northwestern University
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP