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

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)

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.

Study Overview

• Status: Completed
• Conditions: Kidney Failure, Chronic
• Intervention / Treatment: Biological: Mitomycin C-induced peripheral blood mononuclear cells (MICs)

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Baden-Wuerttemberg
    • Heidelberg, Baden-Wuerttemberg, Germany, 69120
      • University of Heidelberg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention arm; Patients receive MIC cell therapy together with standard immunosuppressive therapy	Biological: Mitomycin C-induced peripheral blood mononuclear cells (MICs); MICs are given intravenously 2 or 7 days before kidney transplantation from a living donor

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
Cumulative incidence of infection	30 days
Cumulative incidence of CMV reactivation	30 days
Number of patients with PTLD	30 days
Number of patients with delayed graft function	7 days
Number of patients with a pos. CDC and/or ELISA crossmatch	day -1 before transplantation
Number of patients with DSA	day -1 before transplantation and day 7 and 30 after transplantation
Incidence of biopsy-proven cellular rejection	30 days
Incidence of biopsy-proven antibody-mediated rejection	30 days
Number of patients with stable graft function (S-creatinine < 2mg/dL)	30 days
Patient and graft survival	30 days

Collaborators and Investigators

• Sponsor: Heidelberg University
• Collaborators: WiSP GmbH; German Federal Ministry of Economics and Technology
• Investigators: Principal Investigator: Martin Zeier, MD, Heidelberg University

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 5, 2015
• Primary Completion (Actual): April 18, 2017
• Study Completion (Actual): April 18, 2017

Study Registration Dates

• First Submitted: August 6, 2015
• First Submitted That Met QC Criteria: September 24, 2015
• First Posted (Estimate): September 25, 2015

Study Record Updates

• Last Update Posted (Actual): July 26, 2018
• Last Update Submitted That Met QC Criteria: July 23, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Renal Insufficiency; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Alkylating Agents; Antibiotics, Antineoplastic; Mitomycins; Mitomycin
• Other Study ID Numbers: TOL-1