MIC Cell Therapy for Individualized Immunosuppression in Living Donor Kidney Transplant Recipients

Kidney Failure, Chronic Clinical Trial

— 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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02560220
• Other study ID #: TOL-1
• Status: Completed
• Phase: Phase 1
• Start date: August 5, 2015
• Est. completion date: April 18, 2017

Study information

• Verified date: July 2018
• Source: Heidelberg University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: April 18, 2017
• Est. primary completion date: April 18, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Kidney Failure, Chronic
• Renal Insufficiency

Intervention

Biological:
• Mitomycin C-induced peripheral blood mononuclear cells (MICs)
MICs are given intravenously 2 or 7 days before kidney transplantation from a living donor

Locations

Country	Name	City	State
Germany	University of Heidelberg	Heidelberg	Baden-Wuerttemberg

Sponsors (3)

Lead Sponsor	Collaborator
Heidelberg University	German Federal Ministry of Economics and Technology, WiSP GmbH

Country where clinical trial is conducted

Germany, 

References & Publications (4)

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. — View 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. — View 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. Review. — View Citation

Terness P, Oelert T, Ehser S, Chuang JJ, Lahdou I, Kleist C, Velten F, Hämmerling 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary outcome measure is the frequency of adverse events after intravenous administration of MICs within 30 days after transplantation.		30 days
Secondary	Cumulative incidence of infection		30 days
Secondary	Cumulative incidence of CMV reactivation		30 days
Secondary	Number of patients with PTLD		30 days
Secondary	Number of patients with delayed graft function		7 days
Secondary	Number of patients with a pos. CDC and/or ELISA crossmatch		day -1 before transplantation
Secondary	Number of patients with DSA		day -1 before transplantation and day 7 and 30 after transplantation
Secondary	Incidence of biopsy-proven cellular rejection		30 days
Secondary	Incidence of biopsy-proven antibody-mediated rejection		30 days
Secondary	Number of patients with stable graft function (S-creatinine < 2mg/dL)		30 days
Secondary	Patient and graft survival		30 days