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Trial record 16 of 530 for:    stem cell kidney

TLI, ATG & Hematopoietic Stem Cell Transplantation and Recipient T Regs Therapy in Living Donor Kidney Transplantation

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ClinicalTrials.gov Identifier: NCT03943238
Recruitment Status : Not yet recruiting
First Posted : May 9, 2019
Last Update Posted : May 9, 2019
Sponsor:
Collaborators:
California Institute for Regenerative Medicine (CIRM)
Northwestern University
Information provided by (Responsible Party):
Everett Meyer, Stanford University

Brief Summary:
This study will determine whether a preparatory regimen including total lymphoid irradiation (TLI), anti-thymocyte globulin (ATG) and infusion of the donor hematopoietic stem cells when given along with recipient regulatory T cells (Tregs) will allow for eventual discontinuation of anti-rejection drugs after living donor kidney transplantation.

Condition or disease Intervention/treatment Phase
Living Donor Kidney Transplantation Biological: Infusion of Donor Hematopoetic Stem Cells and Recipient Tregs Phase 1

Detailed Description:
It has been demonstrated that hematopoietic mixed chimerism or the coexistence of both donor and recipient immune cells can lead to tolerance to the graft in absence of graft versus host disease (GVHD). The goal of this pilot study is to determine if recipients of living donor kidney transplant can be successfully withdraw from immunosuppressive drugs. The patients will receive a preparatory regimen consisting of TLI and ATG following their kidney transplantation. Two weeks later, they will receive purified hematopoietic stem cells (CD34+) and Tcells that have been collected 6 weeks prior from their kidney donor. Regulatory T cells (Tregs) that have been collected from the recipient prior to the transplantation and expanded in vitro will be infuse the following day to enhance the chance of engraftment of the donor bone marrow cells. If chimerism develops and persists, the immunosuppressive drug will be tapered and stop. Mycophenolate mofetil (MMF) will be stopped 12 months after transplantation and if the chimerism remains stable, tacrolimus will be stopped 6 months later. The dose of Tregs will be escalated if the % of donor chimerism is not at least 25% during the first 60 days.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 22 participants
Intervention Model: Single Group Assignment
Intervention Model Description: In this phase 1 study, a conditioning regimen of Total Lymphoid Irradiation, Anti-Thymocyte Globulin and Purified Donr CD34+, T cell and Recipient T regulatory Cell Transfusion in Human Leukocyte Antigen Mismatched Living Donor Kidney Transplantation will be studied
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1 Study of Total Lymphoid Irradiation, Anti-Thymocyte Globulin and Purified Donor CD34+, T-cell and Recipient T Regulatory Cell Transfusion in Human Leukocyte Antigen Mismatched Living Donor Kidney Transplantation
Estimated Study Start Date : June 1, 2019
Estimated Primary Completion Date : August 1, 2024
Estimated Study Completion Date : October 1, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Combined kidney/stem cell transplants and recipient's Tregs
Preparatory regimen including TLI, ATG after kidney transplantation followed by infusion of donor CD34+, T cell and recipient Tregs
Biological: Infusion of Donor Hematopoetic Stem Cells and Recipient Tregs
Living donor kidney transplant recipients will receive after a preparatory regimen of total lymphoid irradiation and and anti-thymocyte globulin an infusion of purified donor CD34+ of >10 x10^6 cells /Kg, 100 x 10^6 donor T cell/ Kg and and an escalated dose of recipient Tregs starting at 25 x10^6/Kg.




Primary Outcome Measures :
  1. Count of participants with sustained mixed chimerism of >25% at 18 months [ Time Frame: Month 18 ]
    Chimerism is defined as the co-existence of the immune cell from both the donor and the recipient.

  2. Count of participants able to withdraw from immunosuppressive drugs without evidence of rejection at 18 months [ Time Frame: Month 18 ]

Secondary Outcome Measures :
  1. Count of participants with adverse events associated with the infusion of the Tregs cell product [ Time Frame: up to 2 years ]
  2. Count of participants with bacterial, viral, or fungal infections [ Time Frame: up to 2 years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. All consenting adults who are 18 to 65 years, living donor renal transplant recipients at Stanford University Medical Center or Northwestern Medicine who have a haplotype matched (minimum single Human Leukocyte Antigen - DR locus (HLA-DR) and HLA-A or B match) living related or unrelated donor.
  2. Patients who agree to participate in the study and sign an Informed Consent.
  3. Patients who have no known contraindication to administration of rabbit ATG or radiation.
  4. Males and females of reproductive potential who agree to practice a reliable form of contraception for at least 1 year posttransplant

Exclusion Criteria:

  1. Previous treatment with rabbit ATG or a known allergy to rabbit proteins.
  2. History of malignancy with the exception of non-melanoma skin malignancies.
  3. Pregnant women or nursing mothers.
  4. Serological evidence of HIV, Hepatitis B surface antigen positive (HBsAg+), or Hepatitis C infection. Epstein Barr Virus (EBV) positive to EBV negative.
  5. Leukopenia (with a white blood cell count < 3000/mm3) or thrombocytopenia (with a platelet count < 100,000/mm3).
  6. Panel Reactive Antibody (PRA) greater than 80% or demonstration of historic and/or current donor specific antibody (DSA)
  7. Prior organ transplantation
  8. High risk of primary kidney disease recurrence
  9. Advanced coronary or vascular disease.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03943238


Contacts
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Contact: Asha Shori, CCRP 650-736-0245 ashas@stanford.edu
Contact: Stephan Busque, MD 650-498-6189 sbusque@stanford.edu

Locations
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United States, California
Stanford University Not yet recruiting
Palo Alto, California, United States, 94305
Contact: Asha Shori, CCRP    650-736-0245    ashas@stanford.edu   
Contact: Stephan Busque, MD    650-498-6189    sbusque@stanford.edu   
Principal Investigator: Everett Meyer, MD         
Sub-Investigator: Lowsky Robert, MD         
Sub-Investigator: Hoppe Richard, MD         
Sub-Investigator: Scandling John, MD         
Sub-Investigator: Strober Samuel, MD         
Sub-Investigator: Kent Jensen, PhD         
Principal Investigator: Stephan Busque, MD         
United States, Illinois
Nothwestern University Not yet recruiting
Chicago, Illinois, United States, 60611
Contact: Diane Stare, RN    312-694-0240    diane.stare@northwestern.edu   
Contact: Joseph Leventhal, MD    312-695-8900    jleventh@nm.org   
Sub-Investigator: Jayesh Mehta, MD         
Sub-Investigator: James Mathew, PhD         
Sub-Investigator: Lorenzo Gallon, MD         
Principal Investigator: Joseph Leventhal, MD         
Sponsors and Collaborators
Stanford University
California Institute for Regenerative Medicine (CIRM)
Northwestern University
Investigators
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Study Director: Everett Meyer, MD Stanford University

Publications:
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Responsible Party: Everett Meyer, Principal Investigator, Stanford University
ClinicalTrials.gov Identifier: NCT03943238     History of Changes
Other Study ID Numbers: 50540
First Posted: May 9, 2019    Key Record Dates
Last Update Posted: May 9, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Everett Meyer, Stanford University:
kidney transplant
Immunological Tolerance
Tregs
Stem cells

Additional relevant MeSH terms:
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Antilymphocyte Serum
Immunologic Factors
Physiological Effects of Drugs
Immunosuppressive Agents