Impact of Rituximab Induction and Living Donation on Immunoregulation and Virus Control in Renal Transplantation - Full Text View

Purpose

This project comprises immunological and virological analyses within a prospective clinical study of Rituximab (Rtx)-treated blood group incompatible living donor (LD) renal transplant recipients compared to blood group compatible LD recipients without Rtx induction, and of living donor compared to deceased donor renal transplant recipients treated with tacrolimus (Tacr)/mycophenolate sodium (MPS). Aim of this project is to assess short- and long-term effects of immunosuppressive therapy (Rtx induction) and of living donation on immunological and histological parameters of graft outcome and on viral replication (BK, JC, CMV, EBV) with the potential to improve long-term graft outcome and to enable risk estimation of virus disease.

Condition	Intervention	Phase
Kidney Transplantation Rituximab Living Donors Immunology Virus	Drug: Rituximab Procedure: living donor transplantation Procedure: deceased donor transplantation	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Impact of Rituximab Induction and Living Donation on Immunoregulation and Virus Control in Renal Transplantation - a Prospective Pilot Study

Resource links provided by NLM:

MedlinePlus related topics: Kidney Transplantation

Drug Information available for: Rituximab

U.S. FDA Resources

Further study details as provided by University of Giessen:

Primary Outcome Measures:

Impact of Rtx on immune parameters predictive of graft outcome including B cell responses [ Time Frame: 5 years posttransplant ] [ Designated as safety issue: No ]
immune parameters of graft outcome: see "detailed description"
Impact of living donation on immune parameters predictive of graft outcome including B cell responses [ Time Frame: 5 years posttransplant ] [ Designated as safety issue: No ]
parameters of graft outcome: see "detailed description"
Impact of Rtx on virus replication (EBV, CMV, BK/JC) [ Time Frame: 5 years posttransplant ] [ Designated as safety issue: Yes ]
Impact of living donation on virus replication (EBV, CMV, BK/JC) [ Time Frame: 5 years posttransplant ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Patient and graft survival [ Time Frame: 5 years posttransplant ] [ Designated as safety issue: Yes ]
Graft function and proteinuria [ Time Frame: 5 years posttransplant ] [ Designated as safety issue: Yes ]
Incidence of acute rejection [ Time Frame: 5 years posttransplant ] [ Designated as safety issue: Yes ]
Incidence of chronic allograft dysfunction [ Time Frame: 5 years posttransplant ] [ Designated as safety issue: Yes ]
Incidence of severe infectious disease [ Time Frame: 5 years posttransplant ] [ Designated as safety issue: Yes ]
severe infectious disease as defined by need for in-hospital treatment
Incidence of malignancy [ Time Frame: 5 years posttransplant ] [ Designated as safety issue: Yes ]
Incidence of side effects associated with Rtx [ Time Frame: 5 years posttransplant ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	90
Study Start Date:	January 2010
Estimated Study Completion Date:	July 2018
Estimated Primary Completion Date:	April 2018 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: LD kidney transplantation, ABOi Living donor (LD) kidney transplantation, ABO incompatible (ABOi); Immunosuppressive treatment: Tacrolimus (Tacr)/ Mycophenolate sodium (MPS), Basiliximab induction, Rtx induction	Drug: Rituximab 375mg/m2 4 weeks before ABO incompatible LD transplantation Other Names: ABOi LD NTx Anti-CD20 MoAb
Active Comparator: LD kidney transplantation, ABOc Living donor (LD) kidney transplantation, ABO compatible (ABOc); Immunosuppressive treatment: Tacr/MPS, Basiliximab induction	Procedure: living donor transplantation living donor transplantation (ABO compatible) to be compared with deceased donor transplantation (ABO compatible) in its impact on immunological parameters of graft outcome and on viral replication (CMV, EBV, BK/JC), respectively Other Name: ABOc LD NTx
Active Comparator: DD kidney transplantation Deceased donor (DD) kidney transplantation, ABO compatible; Immunosuppressive treatment: Tacr/MPS, Basiliximab induction	Procedure: deceased donor transplantation deceased donor transplantation (ABO compatible) to be compared with living donor transplantation (ABO compatible) in its impact on immunological parameters of graft outcome and on viral replication (CMV, EBV, BK/JC), respectively Other Name: DD NTx

Show Detailed Description

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

De-novo kidney transplantation
Deceased donors (blood group compatible) and living donors (blood group incompatible / blood group compatible)
First, second and third renal transplants
Immunized and non-immunized graft recipients
Age of recipients 18 years or older
Negative pregnancy test before transplantation

Exclusion Criteria:

Contra-indications to use Tacr and MPS, respectively
Contra-indications to use Rtx in the group of ABOi LD transplants
Chronic hepatitis B, C or HIV infection
Recurrent infectious disease
Previous hepatitis B, if no prophylactic antiviral therapy is used
Previous tuberculosis
Hemoglobin<8,5g/dl, thrombocytes<80.000/ul or leucocytes<3000/ul
Previous vaccination with a living vaccine <4 weeks pretransplant
Significant enterogastric disease such as diverticulitis (contra-indicates MPS treatment)
Children and adolescents (age less than 18 years)
Pregnancy and breast-feeding women
Refusal of an effective contraception in women capable of bearing children
Combined transplantations such as simultaneous islet/kidney transplants

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01136395

Contacts

Contact: Fabrice Renner, MD	++49-641-99-42112	fabrice.renner@innere.med.uni-giessen.de
Contact: Rolf Weimer, Prof. Dr.	++49-641-99-42398	rolf.weimer@innere.med.uni-giessen.de

Locations

Germany
Departments of Surgery and Internal Medicine, University of Freiburg	Not yet recruiting
Freiburg, Germany, D-79106
Contact: Przemyslaw Pisarski, Dr. ++49-761-270-2840 przemyslaw.pisarski@uniklinik-freiburg.de
Contact: Karl-Georg Fischer, PD Dr. ++49-761-270-3424 karl-georg.fischer@uniklinik-freiburg.de
Principal Investigator: Przemyslaw Pisarski, Dr.
Sub-Investigator: karl-georg fischer, PD Dr.
Department of Internal Medicine, University of Giessen	Recruiting
Giessen, Germany, D-35392
Principal Investigator: Rolf Weimer, Prof. Dr.
Sub-Investigator: Fabrice Renner, Dr.

Sponsors and Collaborators

University of Giessen

University Hospital Freiburg

University of Heidelberg

German Cancer Research Center

Astellas Pharma US, Inc.

Novartis

Investigators

Principal Investigator:

Rolf Weimer, Prof. Dr.

University of Giessen, Department of Internal Medicine

More Information

Publications:

Hackstein H, Renner FC, Bohnert A, Nockher A, Frommer T, Bein G, Weimer R. Dendritic cell deficiency in the blood of kidney transplant patients on long-term immunosuppression: results of a prospective matched-cohort study. Am J Transplant. 2005 Dec;5(12):2945-53.

Sadeghi M, Daniel V, Weimer R, Wiesel M, Hergesell O, Opelz G. Differential early posttransplant cytokine responses in living and cadaver donor renal allografts. Transplantation. 2003 Apr 27;75(8):1351-5.

Staak A, Renner F, Suesal C, Dietrich H, Rainer L, Kamali-Ernst S, Ernst W, Padberg W, Opelz G, Weimer R. Immunoglobulin induction therapy in renal transplant recipients: Effects on immunoglobulin and regulatory antibody levels. Transplant Proc. 2006 Dec;38(10):3483-5.

Weimer R, Melk A, Daniel V, Friemann S, Padberg W, Opelz G. Switch from cyclosporine A to tacrolimus in renal transplant recipients: impact on Th1, Th2, and monokine responses. Hum Immunol. 2000 Sep;61(9):884-97.

Weimer R, Mytilineos J, Feustel A, Preiss A, Daniel V, Grimm H, Wiesel M, Opelz G. Mycophenolate mofetil-based immunosuppression and cytokine genotypes: effects on monokine secretion and antigen presentation in long-term renal transplant recipients. Transplantation. 2003 Jun 27;75(12):2090-9.

Weimer R, Staak A, Susal C, Streller S, Yildiz S, Pelzl S, Renner F, Dietrich H, Daniel V, Rainer L, Kamali-Ernst S, Ernst W, Padberg W, Opelz G. ATG induction therapy: long-term effects on Th1 but not on Th2 responses. Transpl Int. 2005 Feb;18(2):226-36.

Weimer R, Susal C, Yildiz S, Staak A, Pelzl S, Renner F, Dietrich H, Daniel V, Kamali-Ernst S, Ernst W, Padberg W, Opelz G. Post-transplant sCD30 and neopterin as predictors of chronic allograft nephropathy: impact of different immunosuppressive regimens. Am J Transplant. 2006 Aug;6(8):1865-74. Epub 2006 Jun 9.

Daniel V, Naujokat C, Sadeghi M, Renner FC, Weimer R, Opelz G. Association of high IFN-gamma plasma levels with low B-cell counts in renal transplant recipients with stable long-term graft function. Clin Transplant. 2010 Mar 1;24(2):281-9. Epub 2009 Aug 27.

Susal C, Dohler B, Opelz G. Graft-protective role of high pretransplantation IgA-anti-Fab autoantibodies: confirmatory evidence obtained in more than 4000 kidney transplants. The Collaborative Transplant Study. Transplantation. 2000 Apr 15;69(7):1337-40.

Susal C, Pelzl S, Dohler B, Opelz G. Identification of highly responsive kidney transplant recipients using pretransplant soluble CD30. J Am Soc Nephrol. 2002 Jun;13(6):1650-6.

Responsible Party:	Prof. Dr. Rolf Weimer, University of Giessen
ClinicalTrials.gov Identifier:	NCT01136395 History of Changes
Other Study ID Numbers:	NTx-RTx-LD-001, 2009-012198-36
Study First Received:	June 2, 2010
Last Updated:	June 2, 2010
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University of Giessen:

Kidney Transplantation
Rituximab
Living Donor
ABO Incompatible Transplantation

Immunology
CMV
EBV
Polyomavirus

Additional relevant MeSH terms:

Virus Diseases
Rituximab
Immunologic Factors
Physiological Effects of Drugs

Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents

ClinicalTrials.gov processed this record on May 16, 2013