Pilot Feasibility Study of Combined Kidney and Hematopoietic Stem Cell Transplantation to Cure End-stage Renal Disease

NCT02176434 | Unknown DMC

• 1 other identifier: swisstolerance.ch
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot study of combined kidney and hematopoietic stem cell transplantation attempts to establish a protocol to induce immunological tolerance as a new strategy to prevent renal graft rejection. If successful, this strategy would restore renal function, while avoiding the risks associated with long-term standard anti-rejection therapy, and would represent the first option to cure end-stage renal disease.

Conditions

End Stage Renal Disease

Keywords

End stage renal disease; Transplantation; Tolerance

Outcome Measures

Primary Outcomes (1)

• Renal allograft acceptance and ability to discontinue immunosuppressive therapy at 1 year

  * Renal function as determined by eGFR (CKD-EPI) and proteinuria after discontinuation of immunosuppressive therapy (1 year after transplantation) * Evidence for rejection according to Banff classification, as assessed in the transplant biopsy performed after discontinuation of immunosuppressive therapy (1 year after transplantation)

  1 year

Secondary Outcomes (6)

• Engraftment of hematopoietic stem cells (chimerism)

  6 months

• Absence of graft versus host disease

  6 and 12 months

• Absence of renal allograft rejection

  6 and 12 months

• T cell recovery and immune reconstitution

  6 and 12 months

• Absence of opportunistic infections (immune competence)

  6 and 12 months

Study Arms (1)

Tolerance

EXPERIMENTAL

Combined kidney and hematopoietic stem cell transplantation from the same donor.

Procedure: Kidney and hematopoietic stem cell transplantation; Biological: hematopoietic stem cell

Interventions

Kidney and hematopoietic stem cell transplantation PROCEDURE

Kidney transplantation (day 0) Induction therapy (s. above) Hematopoietic stem cell transplantation (s. above)

Tolerance

hematopoietic stem cell BIOLOGICAL

Tolerance

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients, who are eligible for kidney transplantation
• Males or females 18 - 70 years of age.
• Subjects must have an HLA-matched sibling donor 25-70 years of age
• Men and women of reproductive potential must agree to use a reliable method of birth control
• Ability to understand and provide informed consent.

You may not qualify if:

• Evidence of uncontrolled active infection (including replicating HIV, Hepatitic B and Hepatitis C) as defined by:
• clinical syndrome consistent with viral or bacterial infection, or
• fever with a clinical site of infection identified, or
• microbiologically documented infection
• Contraindication to therapy with any one of the proposed agents (e.g. allergy to ATG).
• Serologic positivity to HIV.
• Women of childbearing age in whom adequate contraception cannot be maintained, pregnant women or nursing mothers.
• Malignancy within the past two years, for which waiting time for transplantation is required by PENN registry consult, thereby excluding non-melanoma skin cancer and carcinoma in situ of the cervix.
• Liver transaminases \> 3 x normal value.
• Cardiac ejection fraction \< 50% by radionuclide ventriculography or echocardiography.
• Forced Expiratory Volume (FEV1) \< 50% predicted or corrected Diffusing Capacity for Carbon Monoxide (DLCO) \< 50 % predicted.
• Blood group incompatibility in the host-vs-graft direction.
• High risk of primary kidney disease recurrence

Sponsors & Collaborators

• University of Zurich: lead

Study Sites (1)

University Hospital Zurich

Zurich, CH-8091, Switzerland

RECRUITING

Related Publications (1)

• Scandling JD, Busque S, Shizuru JA, Engleman EG, Strober S. Induced immune tolerance for kidney transplantation. N Engl J Med. 2011 Oct 6;365(14):1359-60. doi: 10.1056/NEJMc1107841. No abstract available.

  PMID: 21991976 BACKGROUND

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

Hematopoietic Stem Cell Transplantation

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)

Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• Thomas Ferh, MD

  University of Zurich

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Thomas Fehr, MD

CONTACT

thomas.fehr@uzh.ch

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: June 23, 2014
• First Posted: June 27, 2014
• Study Start: September 1, 2015
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2025
• Last Updated: December 1, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)