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MIC Cell Therapy for Individualized Immunosuppression in Living Donor Kidney Transplant Recipients (TOL-1)

Primary Purpose

Kidney Failure, Chronic

Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
Mitomycin C-induced peripheral blood mononuclear cells (MICs)
Sponsored by
Heidelberg University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Kidney Failure, Chronic

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Chronic kidney disease stage KDIGO 4 or 5
  • First kidney transplant from a living donor
  • Age ≥ 18 years
  • ABO compatible
  • CDC-PRA < 20%
  • No donor-specific antibodies
  • Negative CDC and ELISA crossmatch
  • Immunosuppression with cyclosporin A, EC-MPS and methylprednisolone
  • Informed consent
  • Adequate contraception (women with child bearing potential)

Exclusion Criteria:

  • Psychiatric disorder
  • Heart failure (NYHA III or IV)
  • Severe liver disease
  • Active hepatitis B or C or HIV infection
  • Active bacterial, fungal or viral disease
  • Malignancy or malignancy in the last 5 years before screening
  • Preexisting immunosuppression
  • Vaccination with a live vaccine in the last 3 months before screening
  • S/p splenectomy
  • Substance abuse
  • Pregnancy or lactation
  • Women: Child/pregnancy with the intended donor
  • Allergy against the investigational drug or part of it
  • Other diseases that prohibit participation in the study (in the opinion of the investigator)
  • Participation in an other interventional study

Sites / Locations

  • University of Heidelberg

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Intervention arm

Arm Description

Patients receive MIC cell therapy together with standard immunosuppressive therapy

Outcomes

Primary Outcome Measures

The primary outcome measure is the frequency of adverse events after intravenous administration of MICs within 30 days after transplantation.

Secondary Outcome Measures

Cumulative incidence of infection
Cumulative incidence of CMV reactivation
Number of patients with PTLD
Number of patients with delayed graft function
Number of patients with a pos. CDC and/or ELISA crossmatch
Number of patients with DSA
Incidence of biopsy-proven cellular rejection
Incidence of biopsy-proven antibody-mediated rejection
Number of patients with stable graft function (S-creatinine < 2mg/dL)
Patient and graft survival

Full Information

First Posted
August 6, 2015
Last Updated
July 23, 2018
Sponsor
Heidelberg University
Collaborators
WiSP GmbH, German Federal Ministry of Economics and Technology
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1. Study Identification

Unique Protocol Identification Number
NCT02560220
Brief Title
MIC Cell Therapy for Individualized Immunosuppression in Living Donor Kidney Transplant Recipients
Acronym
TOL-1
Official Title
A Single-arm Phase-I Trial for the Determination of Safety and Feasibility of the Intravenous Administration of Mitomycin C-treated Donor Peripheral Blood Mononuclear Cells (MICs) for Individualized Immunosuppression in Living Donor Kidney Transplant Recipients (TOL-1 Study)
Study Type
Interventional

2. Study Status

Record Verification Date
July 2018
Overall Recruitment Status
Completed
Study Start Date
August 5, 2015 (Actual)
Primary Completion Date
April 18, 2017 (Actual)
Study Completion Date
April 18, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Heidelberg University
Collaborators
WiSP GmbH, German Federal Ministry of Economics and Technology

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
A phase- I clinical trial to determine safety and feasibilty of intravenous administration of mitomycin C-treated donor peripheral blood mononuclear cells in patients with chronic kidney disease stage KDIGO 4 or 5 (i.e. GFR 15-30 mL/min or < 15 mL/min) who receive a kidney transplant from a living donor.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Kidney Failure, Chronic

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
14 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Intervention arm
Arm Type
Experimental
Arm Description
Patients receive MIC cell therapy together with standard immunosuppressive therapy
Intervention Type
Biological
Intervention Name(s)
Mitomycin C-induced peripheral blood mononuclear cells (MICs)
Intervention Description
MICs are given intravenously 2 or 7 days before kidney transplantation from a living donor
Primary Outcome Measure Information:
Title
The primary outcome measure is the frequency of adverse events after intravenous administration of MICs within 30 days after transplantation.
Time Frame
30 days
Secondary Outcome Measure Information:
Title
Cumulative incidence of infection
Time Frame
30 days
Title
Cumulative incidence of CMV reactivation
Time Frame
30 days
Title
Number of patients with PTLD
Time Frame
30 days
Title
Number of patients with delayed graft function
Time Frame
7 days
Title
Number of patients with a pos. CDC and/or ELISA crossmatch
Time Frame
day -1 before transplantation
Title
Number of patients with DSA
Time Frame
day -1 before transplantation and day 7 and 30 after transplantation
Title
Incidence of biopsy-proven cellular rejection
Time Frame
30 days
Title
Incidence of biopsy-proven antibody-mediated rejection
Time Frame
30 days
Title
Number of patients with stable graft function (S-creatinine < 2mg/dL)
Time Frame
30 days
Title
Patient and graft survival
Time Frame
30 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Chronic kidney disease stage KDIGO 4 or 5 First kidney transplant from a living donor Age ≥ 18 years ABO compatible CDC-PRA < 20% No donor-specific antibodies Negative CDC and ELISA crossmatch Immunosuppression with cyclosporin A, EC-MPS and methylprednisolone Informed consent Adequate contraception (women with child bearing potential) Exclusion Criteria: Psychiatric disorder Heart failure (NYHA III or IV) Severe liver disease Active hepatitis B or C or HIV infection Active bacterial, fungal or viral disease Malignancy or malignancy in the last 5 years before screening Preexisting immunosuppression Vaccination with a live vaccine in the last 3 months before screening S/p splenectomy Substance abuse Pregnancy or lactation Women: Child/pregnancy with the intended donor Allergy against the investigational drug or part of it Other diseases that prohibit participation in the study (in the opinion of the investigator) Participation in an other interventional study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Martin Zeier, MD
Organizational Affiliation
Heidelberg University
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Heidelberg
City
Heidelberg
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
69120
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
26077202
Citation
Morath C, Schmitt A, Zeier M, Schmitt M, Sandra-Petrescu F, Opelz G, Terness P, Schaier M, Kleist C. Cell therapy for immunosuppression after kidney transplantation. Langenbecks Arch Surg. 2015 Jul;400(5):541-50. doi: 10.1007/s00423-015-1313-z. Epub 2015 Jun 17.
Results Reference
background
PubMed Identifier
25495457
Citation
Kleist C, Sandra-Petrescu F, Jiga L, Dittmar L, Mohr E, Greil J, Mier W, Becker LE, Lang P, Opelz G, Terness P. Generation of suppressive blood cells for control of allograft rejection. Clin Sci (Lond). 2015 May;128(9):593-607. doi: 10.1042/CS20140258.
Results Reference
background
PubMed Identifier
26074415
Citation
Dittmar L, Mohr E, Kleist C, Ehser S, Demirdizen H, Sandra-Petrescu F, Hundemer M, Opelz G, Terness P. Immunosuppressive properties of mitomycin C-incubated human myeloid blood cells (MIC) in vitro. Hum Immunol. 2015 Jul;76(7):480-7. doi: 10.1016/j.humimm.2015.06.008. Epub 2015 Jun 11.
Results Reference
background
PubMed Identifier
19017789
Citation
Terness P, Oelert T, Ehser S, Chuang JJ, Lahdou I, Kleist C, Velten F, Hammerling GJ, Arnold B, Opelz G. Mitomycin C-treated dendritic cells inactivate autoreactive T cells: toward the development of a tolerogenic vaccine in autoimmune diseases. Proc Natl Acad Sci U S A. 2008 Nov 25;105(47):18442-7. doi: 10.1073/pnas.0807185105. Epub 2008 Nov 18.
Results Reference
background
PubMed Identifier
31990685
Citation
Morath C, Schmitt A, Kleist C, Daniel V, Opelz G, Susal C, Ibrahim E, Kalble F, Speer C, Nusshag C, Pego da Silva L, Sommerer C, Wang L, Ni M, Huckelhoven-Krauss A, Czock D, Merle U, Mehrabi A, Sander A, Hackbusch M, Eckert C, Waldherr R, Schnitzler P, Muller-Tidow C, Hoheisel JD, Mustafa SA, Alhamdani MS, Bauer AS, Reiser J, Zeier M, Schmitt M, Schaier M, Terness P. Phase I trial of donor-derived modified immune cell infusion in kidney transplantation. J Clin Invest. 2020 May 1;130(5):2364-2376. doi: 10.1172/JCI133595.
Results Reference
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MIC Cell Therapy for Individualized Immunosuppression in Living Donor Kidney Transplant Recipients

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