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

N/AUnknownNCT02199301

Samsung Medical Center6 enrolled

Overview

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 IS will be tapered slowly and withdrawn over a period of several months.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

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

End Stage Renal Disease

Interventions

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)

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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.

Time frame: Immune Suppression Withdrawal within 18 months post-transplantation

Secondary Outcomes

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.

Time frame: 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.