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

End Stage Renal Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02199301
• Other study ID #: 2010-07-210
• Status: Recruiting
• Phase: N/A
• First received: September 10, 2012
• Last updated: July 22, 2014
• Start date: December 2011
• Est. completion date: December 2017

Study information

• Verified date: September 2012
• Source: Samsung Medical Center
• Contact: Sung Joo Kim, MD, PhD
• Phone: 82-2-3410-3476
• Email: kmhyj.kim[@]samsung.com
• Is FDA regulated: No
• Health authority: South Korea: Institutional Review Board
• Study type: Interventional

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 IS will be tapered slowly and withdrawn over a period of several months.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 6
• Est. completion date: December 2017
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• End Stage Renal Disease
• Kidney Failure, Chronic

Intervention

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)

Locations

Country	Name	City	State
Korea, Republic of	Samsung Medical Center, Organ Transplant Center	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Samsung Medical Center

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Microchimerism	Presence and proportion of microchimerism in recipient's peripheral blood will be measured by microsatellite short tandem repeat.	At post-transplantation 1, 2, 3, 4, 8, and 24 wks	No
Other	Immune Cell Profiling	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.	At post-transplantation 1, 2, 4, 8, 12, 24, and 52 weeks	No
Other	Mixed Lymphocyte Reaction	Mixed lymphocyte reaction will be done for the evaluation for the donor-specific immune response (Donor vs. 3rd party) in vitro.	At post-transplantation 8, 24, 52 weeks	No
Other	Protocol Biopsy	Absence or presence of allograft rejection is confirmed by ultrasonography-guided percutaneous biopsy during follow-up and prior to withdrawal of immunosuppressive agent.	Post-transplantation 3, 24, and 52 weeks	No
Primary	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	No
Secondary	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	Yes
Secondary	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	No