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

Study Overview
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Brief Summary
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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 IS will be tapered slowly and withdrawn over a period of several months.

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

Conditions
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End Stage Renal Disease

Intervention / Treatment
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* Procedure: Transplantation Conditioning for BMT


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BMTKT<br>Transplantation Conditioning for bone marrow transplantation (BMT) Kidney transplantation and BMT (BMTKT) | Procedure: Transplantation Conditioning for BMT<br>* 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)<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kidney transplantation, Tolerance induction, Immunosuppression withdrawal, Bone marrow transplantation, Transplantation conditioning, Hematopoietic stem cell transplantation, Living donor, Haplotype, Immune tolerance