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

July 22, 2014 updated by: Samsung Medical Center

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 IS will be tapered slowly and withdrawn over a period of several months.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

6

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Korea, Republic of
      • Seoul, Korea, Republic of, 135-710
        • Recruiting
        • Samsung Medical Center, Organ Transplant Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Immune Suppression Withdrawal within 18 months post-transplantation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
At the post-transplantation 18 months
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.
At the post-transplantation 18 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
At post-transplantation 1, 2, 3, 4, 8, and 24 wks
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.
At post-transplantation 1, 2, 4, 8, 12, 24, and 52 weeks
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.
At post-transplantation 8, 24, 52 weeks
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.
Post-transplantation 3, 24, and 52 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Samsung Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2011

Primary Completion (Anticipated)

December 1, 2015

Study Completion (Anticipated)

December 1, 2017

Study Registration Dates

First Submitted

September 10, 2012

First Submitted That Met QC Criteria

July 22, 2014

First Posted (Estimate)

July 24, 2014

Study Record Updates

Last Update Posted (Estimate)

July 24, 2014

Last Update Submitted That Met QC Criteria

July 22, 2014

Last Verified

September 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2010-07-210

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on End Stage Renal Disease

Clinical Trials on Transplantation Conditioning for BMT

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Trinidad & Tobago

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe