Clinical trial NCT02560220: MIC Cell Therapy for Individualized Immunosuppression in Living Donor Kidney Transplant Recipients
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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Kidney Failure, Chronic
Lead sponsor: Heidelberg University
Sponsor class: OTHER
Collaborators: name: WiSP GmbH
name: German Federal Ministry of Economics and Technology
First posted: 2015-09-25
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.


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

Primary outcomes:
measure: The primary outcome measure is the frequency of adverse events after intravenous administration of MICs within 30 days after transplantation.
timeFrame: 30 days
Secondary outcomes:
measure: Cumulative incidence of infection
timeFrame: 30 days
measure: Cumulative incidence of CMV reactivation
timeFrame: 30 days
measure: Number of patients with PTLD
timeFrame: 30 days
measure: Number of patients with delayed graft function
timeFrame: 7 days
measure: Number of patients with a pos. CDC and/or ELISA crossmatch
timeFrame: day -1 before transplantation
measure: Number of patients with DSA
timeFrame: day -1 before transplantation and day 7 and 30 after transplantation
measure: Incidence of biopsy-proven cellular rejection
timeFrame: 30 days
measure: Incidence of biopsy-proven antibody-mediated rejection
timeFrame: 30 days
measure: Number of patients with stable graft function (S-creatinine < 2mg/dL)
timeFrame: 30 days
measure: Patient and graft survival
timeFrame: 30 days
Other outcomes:
Locations:
city: Heidelberg
country: Germany
facility: University of Heidelberg
state: Baden-Wuerttemberg
Study officials:
affiliation: Heidelberg University
name: Martin Zeier, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.