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

Sponsor

Samsung Medical Center (Other)

Overall Status

Unknown status

CT.gov ID

NCT02199301

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

0.1

Patients Per Site Per Month

Study Details

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 IS will be tapered slowly and withdrawn over a period of several months.

Condition or Disease	Intervention/Treatment	Phase
End Stage Renal Disease	Procedure: Transplantation Conditioning for BMT	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

6 participants

Allocation:

N/A

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 :

Dec 1, 2011

Anticipated Primary Completion Date :

Dec 1, 2015

Anticipated Study Completion Date :

Dec 1, 2017

Arms and Interventions

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)

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)

Outcome Measures

Primary Outcome Measures

Immune Suppression Withdrawal [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

Graft failure [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.
Allograft Rejection [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

Microchimerism [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.
Immune Cell Profiling [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.
Mixed Lymphocyte Reaction [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.
Protocol Biopsy [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.