Clinical trial NCT02199301: 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
Overall status: UNKNOWN
Phase: NA
Conditions: 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
Lead sponsor: Samsung Medical Center
Sponsor class: OTHER
First posted: 2014-07-24
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 IS will be tapered slowly and withdrawn over a period of several months.


Eligibility criteria: 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.

Primary outcomes:
measure: Immune Suppression Withdrawal
timeFrame: Immune Suppression Withdrawal within 18 months post-transplantation
Secondary outcomes:
measure: Graft failure
timeFrame: At the post-transplantation 18 months
measure: Allograft Rejection
timeFrame: At the post-transplantation 18 months
Other outcomes:
measure: Microchimerism
timeFrame: At post-transplantation 1, 2, 3, 4, 8, and 24 wks
measure: Immune Cell Profiling
timeFrame: At post-transplantation 1, 2, 4, 8, 12, 24, and 52 weeks
measure: Mixed Lymphocyte Reaction
timeFrame: At post-transplantation 8, 24, 52 weeks
measure: Protocol Biopsy
timeFrame: Post-transplantation 3, 24, and 52 weeks
Locations:
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center, Organ Transplant Center
Study officials:
References: