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

NCT02199301 | Unknown

• 1 other identifier: 2010-07-210
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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 IS will be tapered slowly and withdrawn over a period of several months.

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

Outcome Measures

Primary Outcomes (1)

• 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  Immune suppression will be tapered-off and withdrawn over the period of 6 to 18 months post-transplantation under the monitoring of graft function and immunologic measurements.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 Outcomes (2)

• Graft failure

  At the post-transplantation 18 months

• Allograft Rejection

  At the post-transplantation 18 months

Other Outcomes (4)

• Microchimerism

  At post-transplantation 1, 2, 3, 4, 8, and 24 wks

• Immune Cell Profiling

  At post-transplantation 1, 2, 4, 8, 12, 24, and 52 weeks

• Mixed Lymphocyte Reaction

  At post-transplantation 8, 24, 52 weeks

Study Arms (1)

BMTKT

EXPERIMENTAL

Transplantation Conditioning for bone marrow transplantation (BMT) Kidney transplantation and BMT (BMTKT)

Procedure: Transplantation Conditioning for BMT

Interventions

Transplantation Conditioning for BMT PROCEDURE

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)

BMTKT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Samsung Medical Center: lead

Study Sites (1)

Samsung Medical Center, Organ Transplant Center

Seoul, 135-710, South Korea

RECRUITING

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

Transplantation Conditioning

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Immunosuppression Therapy; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques

Central Study Contacts

Sung Joo Kim, MD, PhD

CONTACT

82-2-3410-3476; kmhyj.kim@samsung.com

Jae Berm Park, MD, PhD

CONTACT

82-2-3410-3647; jbparkmd@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2012
• First Posted: July 24, 2014
• Study Start: December 1, 2011
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2017
• Last Updated: July 24, 2014

Record last verified: 2012-09

Locations

KR (1)