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

Primary Purpose

End Stage Renal Disease

Status
Unknown status
Phase
Not Applicable
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Transplantation Conditioning for BMT
Sponsored by
Samsung Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for End Stage Renal Disease focused on measuring Kidney transplantation, Tolerance induction, Immunosuppression withdrawal, Bone marrow transplantation, Transplantation conditioning, Hematopoietic stem cell transplantation, Living donor, Haplotype, Immune tolerance

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Samsung Medical Center, Organ Transplant CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

BMTKT

Arm Description

Transplantation Conditioning for bone marrow transplantation (BMT) Kidney transplantation and BMT (BMTKT)

Outcomes

Primary Outcome Measures

Immune Suppression Withdrawal
Immune suppression will be tapered-off and withdrawn over the period of 6 to 18 months post-transplantation under the monitoring of graft function and immunologic measurements.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

Graft failure
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.
Allograft Rejection
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.

Full Information

First Posted
September 10, 2012
Last Updated
July 22, 2014
Sponsor
Samsung Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT02199301
Brief Title
Tolerance Induction in Living Donor Kidney Transplantation With Hematopoietic Stem Cell Transplantation
Official Title
Tolerance Induction in Living Donor Kidney Transplantation With Hematopoietic Stem Cell Transplantation
Study Type
Interventional

2. Study Status

Record Verification Date
September 2012
Overall Recruitment Status
Unknown status
Study Start Date
December 2011 (undefined)
Primary Completion Date
December 2015 (Anticipated)
Study Completion Date
December 2017 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Samsung Medical Center

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
End Stage Renal Disease
Keywords
Kidney transplantation, Tolerance induction, Immunosuppression withdrawal, Bone marrow transplantation, Transplantation conditioning, Hematopoietic stem cell transplantation, Living donor, Haplotype, Immune tolerance

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
BMTKT
Arm Type
Experimental
Arm Description
Transplantation Conditioning for bone marrow transplantation (BMT) Kidney transplantation and BMT (BMTKT)
Intervention Type
Procedure
Intervention Name(s)
Transplantation Conditioning for BMT
Intervention Description
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 Measure Information:
Title
Immune Suppression Withdrawal
Description
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.
Time Frame
Immune Suppression Withdrawal within 18 months post-transplantation
Secondary Outcome Measure Information:
Title
Graft failure
Description
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.
Time Frame
At the post-transplantation 18 months
Title
Allograft Rejection
Description
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.
Time Frame
At the post-transplantation 18 months
Other Pre-specified Outcome Measures:
Title
Microchimerism
Description
Presence and proportion of microchimerism in recipient's peripheral blood will be measured by microsatellite short tandem repeat.
Time Frame
At post-transplantation 1, 2, 3, 4, 8, and 24 wks
Title
Immune Cell Profiling
Description
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.
Time Frame
At post-transplantation 1, 2, 4, 8, 12, 24, and 52 weeks
Title
Mixed Lymphocyte Reaction
Description
Mixed lymphocyte reaction will be done for the evaluation for the donor-specific immune response (Donor vs. 3rd party) in vitro.
Time Frame
At post-transplantation 8, 24, 52 weeks
Title
Protocol Biopsy
Description
Absence or presence of allograft rejection is confirmed by ultrasonography-guided percutaneous biopsy during follow-up and prior to withdrawal of immunosuppressive agent.
Time Frame
Post-transplantation 3, 24, and 52 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: All consenting adult (18 and more years of age) living donor kidney transplant recipients who have a one haplotype match donor. Patients who have no known contraindication to administration of rabbit anti-thymocyte globulin (ATG) or radiation. Patients who agree to participate in the study and sign an Informed Consent. Exclusion Criteria: Presence of previous episode of transplantation including kidney Simultaneous multi-visceral transplantation Demonstration of donor specific antibody (DSA) or panel reactive antibody(PRA) greater than 20% ABO blood type incompatible Previous treatment with rabbit anti-thymocyte globulin or a known allergy to rabbit proteins. History of malignancy with the exception of non-melanoma skin malignancies. Uncontrolled systemic or concomitant unstable infection Serological evidence of Hepatitis B or Hepatitis C or HIV infection. Severe psychiatric disease Leukopenia (with a white blood cell count < 3000/mm3) Disagreement to participate in the study and sign an Informed Consent.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sung Joo Kim, MD, PhD
Phone
82-2-3410-3476
Email
kmhyj.kim@samsung.com
First Name & Middle Initial & Last Name or Official Title & Degree
Jae Berm Park, MD, PhD
Phone
82-2-3410-3647
Email
jbparkmd@gmail.com
Facility Information:
Facility Name
Samsung Medical Center, Organ Transplant Center
City
Seoul
ZIP/Postal Code
135-710
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sung Joo Kim, MD, PhD
Phone
82-2-3410-3476
Email
kmhyj.kim@samsung.com
First Name & Middle Initial & Last Name & Degree
Jae Berm Park, MD, PhD
Phone
82-2-3410-3647
Email
jbparkmd@gmail.com
First Name & Middle Initial & Last Name & Degree
Sung Joo Kim, MD, PhD
First Name & Middle Initial & Last Name & Degree
Jae Berm Park, MD, PhD

12. IPD Sharing Statement

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

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