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Tolerance Induction in Living Donor Kidney Transplantation With Hematopoietic Stem Cell Transplantation

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ClinicalTrials.gov Identifier: NCT02199301
Recruitment Status : Unknown
Verified September 2012 by Samsung Medical Center.
Recruitment status was:  Recruiting
First Posted : July 24, 2014
Last Update Posted : July 24, 2014
Sponsor:
Information provided by (Responsible Party):
Samsung Medical Center

Brief Summary:

Kidney transplantation (KT) requires a life-long immune suppression (IS). It has been well-known that long-term IS inevitably causes various complication e.g. infection, toxicity, diabetes, osteoporosis, avascular necrosis of hip joint, cataract, acne, and malignancies and so on. Tolerance induction showing graft function without maintenance IS has been considered as a final solution in the transplantation recipients. Tolerance induction can be achieved in KT recipients with donor hematopoietic stem cell transplantation (HSCT).

In this study, adult patients (18 and more years of age) with a human leukocyte antigen (HLA)-haplotype match donor are enrolled. Patients receive preconditioning treatment for HSCT 1week prior to KT. Bone marrow is harvested from donor under general anesthesia at the time of nephrectomy for transplantation in donor. Donor BM is infused immediate post-transplantation at intensive care unit (ICU). Immunologic measurements including microchimerism study and protocol biopsy will be followed at several time points. IS will be tapered slowly and withdrawn over a period of several months.


Condition or disease Intervention/treatment Phase
End Stage Renal Disease Procedure: Transplantation Conditioning for BMT Not Applicable

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 6 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Tolerance Induction in Living Donor Kidney Transplantation With Hematopoietic Stem Cell Transplantation
Study Start Date : December 2011
Estimated Primary Completion Date : December 2015
Estimated Study Completion Date : December 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: BMTKT
Transplantation Conditioning for bone marrow transplantation (BMT) Kidney transplantation and BMT (BMTKT)
Procedure: Transplantation Conditioning for BMT
Transplantation Conditioning for BMT (POD#-7~-1) POD#-7: Rituximab (Mabthera, Roche Pharma Aktiengesellschaft (AG) Swiss) 375/m2 iv infusion POD#-6~-3: Fludarabine (Fludara Inj., Bayer AG, Germany) 30mg/m2/day iv infusion POD#-5~-4: Cyclophosphamide (Endoxan Inj., Baxter Oncology Gesellschaft mit beschränkter Haftung (GmbH), Germany) 30mg/kg/day iv infusion POD#-2: (Rituximab 375/m2 iv infusion) POD#-1: Thymic irradiation (Dose, 700cGy)




Primary Outcome Measures :
  1. Immune Suppression Withdrawal [ Time Frame: Immune Suppression Withdrawal within 18 months post-transplantation ]
    Immune suppression will be tapered-off and withdrawn over the period of 6 to 18 months post-transplantation under the monitoring of graft function and immunologic measurements.


Secondary Outcome Measures :
  1. Graft failure [ Time Frame: At the post-transplantation 18 months ]
    In this study, immune suppression(IS) will be tapered-off and withdrawn over the period of 6 to 18 months post-transplantation under the monitoring of graft function and immunologic measurements. At the post-transplantation 18 months we evaluate graft failure episode irrespective of IS withdrawal.

  2. Allograft Rejection [ Time Frame: At the post-transplantation 18 months ]
    In this study, immune suppression(IS) will be tapered-off and withdrawn over the period of 6 to 18 months post-transplantation under the monitoring of graft function and immunologic measurements. At the post-transplantation 18 months we evaluate allograft rejection episode irrespective of IS withdrawal.


Other Outcome Measures:
  1. Microchimerism [ Time Frame: At post-transplantation 1, 2, 3, 4, 8, and 24 wks ]
    Presence and proportion of microchimerism in recipient's peripheral blood will be measured by microsatellite short tandem repeat.

  2. Immune Cell Profiling [ Time Frame: At post-transplantation 1, 2, 4, 8, 12, 24, and 52 weeks ]
    Changes of proportion or absolute count of immune cells are measured by flowcytometric analysis in recipient's peripheral blood, using cluster of differentiation (CD) marker.

  3. Mixed Lymphocyte Reaction [ Time Frame: At post-transplantation 8, 24, 52 weeks ]
    Mixed lymphocyte reaction will be done for the evaluation for the donor-specific immune response (Donor vs. 3rd party) in vitro.

  4. Protocol Biopsy [ Time Frame: Post-transplantation 3, 24, and 52 weeks ]
    Absence or presence of allograft rejection is confirmed by ultrasonography-guided percutaneous biopsy during follow-up and prior to withdrawal of immunosuppressive agent.



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

Inclusion Criteria:

  1. All consenting adult (18 and more years of age) living donor kidney transplant recipients who have a one haplotype match donor.
  2. Patients who have no known contraindication to administration of rabbit anti-thymocyte globulin (ATG) or radiation.
  3. Patients who agree to participate in the study and sign an Informed Consent.

Exclusion Criteria:

  1. Presence of previous episode of transplantation including kidney
  2. Simultaneous multi-visceral transplantation
  3. Demonstration of donor specific antibody (DSA) or panel reactive antibody(PRA) greater than 20%
  4. ABO blood type incompatible
  5. Previous treatment with rabbit anti-thymocyte globulin or a known allergy to rabbit proteins.
  6. History of malignancy with the exception of non-melanoma skin malignancies.
  7. Uncontrolled systemic or concomitant unstable infection
  8. Serological evidence of Hepatitis B or Hepatitis C or HIV infection.
  9. Severe psychiatric disease
  10. Leukopenia (with a white blood cell count < 3000/mm3)
  11. Disagreement to participate in the study and sign an Informed Consent.

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): NCT02199301


Contacts
Contact: Sung Joo Kim, MD, PhD 82-2-3410-3476 kmhyj.kim@samsung.com
Contact: Jae Berm Park, MD, PhD 82-2-3410-3647 jbparkmd@gmail.com

Locations
Korea, Republic of
Samsung Medical Center, Organ Transplant Center Recruiting
Seoul, Korea, Republic of, 135-710
Contact: Sung Joo Kim, MD, PhD    82-2-3410-3476    kmhyj.kim@samsung.com   
Contact: Jae Berm Park, MD, PhD    82-2-3410-3647    jbparkmd@gmail.com   
Principal Investigator: Sung Joo Kim, MD, PhD         
Sub-Investigator: Jae Berm Park, MD, PhD         
Sponsors and Collaborators
Samsung Medical Center

Responsible Party: Samsung Medical Center
ClinicalTrials.gov Identifier: NCT02199301     History of Changes
Other Study ID Numbers: 2010-07-210
First Posted: July 24, 2014    Key Record Dates
Last Update Posted: July 24, 2014
Last Verified: September 2012

Keywords provided by Samsung Medical Center:
Kidney transplantation
Tolerance induction
Immunosuppression withdrawal
Bone marrow transplantation
Transplantation conditioning
Hematopoietic stem cell transplantation
Living donor
Haplotype
Immune tolerance

Additional relevant MeSH terms:
Kidney Failure, Chronic
Renal Insufficiency, Chronic
Renal Insufficiency
Kidney Diseases
Urologic Diseases