HLA-Identical Sibling Renal Transplant Tolerance

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Northwestern University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Joshua Miller, Northwestern University
ClinicalTrials.gov Identifier:
NCT00619528
First received: February 8, 2008
Last updated: June 11, 2014
Last verified: June 2014
  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.


Condition Intervention
Immunosuppression
Kidney Transplantation
Graft Rejection
Biological: Infusion of Donor Hematopoietic Stem Cells and Campath-1H

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: HLA-Identical Sibling Renal Transplant Tolerance With Donor Hematopoietic Stem Cells and Campath-1H

Resource links provided by NLM:


Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
  • Patient and graft survival measured at the one-year timepoint post-transplant. [ Time Frame: One Year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Patient and graft survival measured at the three year timepoint post-transplant.. [ Time Frame: Three years post-transplant. ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Incidence of graft versus host disease (GVHD). [ Time Frame: Up to 5 years Post-Transplant ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 230
Study Start Date: July 2007
Estimated Study Completion Date: February 2021
Estimated Primary Completion Date: February 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
No separate arms: All Enrolled Receive Same Treatment
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.

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).
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00619528

Contacts
Contact: Joshua Miller, MD (312) 503-1801 joshuamiller@northwestern.edu

Locations
United States, Illinois
Northwestern Memorial Hospital Recruiting
Chicago, Illinois, United States, 60611
Contact: jane l charette, RN, RN, BSN, CCRC    312-694-0238    jane-charette@northwestern.edu   
Principal Investigator: Joshua Miller, MD         
Sub-Investigator: Joseph Leventhal, MD         
Sub-Investigator: James Mathew, PhD         
Sub-Investigator: Michael Abecassis, MD         
Sub-Investigator: Richard Burt, MD         
Sub-Investigator: Lorenzo Gallon, MD         
Sub-Investigator: Charles Goolsby, PhD         
Sub-Investigator: Yashpal Kanwar, MD         
Sub-Investigator: Anat Tambur, DMD, PhD         
Sponsors and Collaborators
Northwestern University
Investigators
Principal Investigator: Joshua Miller, MD Northwestern University
  More Information

No publications provided

Responsible Party: Joshua Miller, Professor, Department of Surgery, Division of Organ Transplantation, Feinberg School of Medicine; Director, Immune Tolerance Core, Comprehensive Transplant Center, Northwestern University
ClinicalTrials.gov Identifier: NCT00619528     History of Changes
Other Study ID Numbers: 2R01DK025243-25A2, R01DK025243
Study First Received: February 8, 2008
Last Updated: June 11, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Northwestern University:
Transplants
Kidney Transplantation
Immunosuppression
HLA Antigens
Stem Cells
Bone Marrow

Additional relevant MeSH terms:
Alemtuzumab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 25, 2014