Impact of Rituximab (RTx) Induction and Living Donation on Immunoregulation and Virus Control in Renal Transplantation
Impact of Rituximab Induction and Living Donation on Immunoregulation and Virus Control in Renal Transplantation - a Prospective Pilot Study
2 other identifiers
interventional
85
1 country
1
Brief Summary
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 virus (BKV), JC virus (JCV), cytomegalovirus (CMV), Epstein Barr virus (EBV)) with the potential to improve long-term graft outcome and to enable risk estimation of virus disease.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Jan 2010
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
January 1, 2010
CompletedFirst Submitted
Initial submission to the registry
June 2, 2010
CompletedFirst Posted
Study publicly available on registry
June 3, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 18, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
June 18, 2019
CompletedOctober 8, 2019
October 1, 2019
9.5 years
June 2, 2010
October 7, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (14)
Impact of Rtx on immune parameters predictive of graft outcome including B cell responses
immune parameters of graft outcome: see "detailed description"
5 years posttransplant
Impact of living donation on immune parameters predictive of graft outcome including B cell responses
parameters of graft outcome: see "detailed description"
5 years posttransplant
Impact of Rtx on virus replication
outcome measure description: EBV PCR (in blood)
5 years posttransplant
Impact of Rtx on virus replication
outcome measure description: CMV PCR (in blood)
5 years posttransplant
Impact of Rtx on virus replication
outcome measure description: BKV PCR (in blood)
5 years posttransplant
Impact of Rtx on virus replication
outcome measure description: BKV PCR (in urine)
5 years posttransplant
Impact of Rtx on virus replication
outcome measure description: JCV PCR (in blood)
5 years posttransplant
Impact of Rtx on virus replication
outcome measure description: JCV PCR (in urine)
5 years posttransplant
Impact of living donation on virus replication
outcome measure description: EBV PCR (in blood)
5 years posttransplant
Impact of living donation on virus replication
outcome measure description: CMV PCR (in blood)
5 years posttransplant
Impact of living donation on virus replication
outcome measure description: BKV PCR (in blood)
5 years posttransplant
Impact of living donation on virus replication
outcome measure description: BKV PCR (in urine)
5 years posttransplant
Impact of living donation on virus replication
outcome measure description: JCV PCR (in blood)
5 years posttransplant
Impact of living donation on virus replication
outcome measure description: JCV PCR (in urine)
5 years posttransplant
Secondary Outcomes (13)
Patient survival
5 years posttransplant
Graft survival
5 years posttransplant
Graft function and proteinuria
5 years posttransplant
Graft function
5 years posttransplant
Graft function
5 years posttransplant
- +8 more secondary outcomes
Study Arms (3)
LD kidney transplantation, ABOi
ACTIVE COMPARATORLiving donor (LD) kidney transplantation, ABO incompatible (ABOi); Immunosuppressive treatment: Tacrolimus (Tacr)/ Mycophenolate sodium (MPS), Basiliximab induction, Rtx induction
LD kidney transplantation, ABOc
ACTIVE COMPARATORLiving donor (LD) kidney transplantation, ABO compatible (ABOc); Immunosuppressive treatment: Tacr/MPS, Basiliximab induction
DD kidney transplantation
ACTIVE COMPARATORDeceased donor (DD) kidney transplantation, ABO compatible; Immunosuppressive treatment: Tacr/MPS, Basiliximab induction
Interventions
375mg/m2 4 weeks before ABOi LD 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
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 virus (BKV), JC virus (JCV)), respectively
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Giessenlead
- Heidelberg Universitycollaborator
- German Cancer Research Centercollaborator
- Astellas Pharma US, Inc.collaborator
- Novartiscollaborator
Study Sites (1)
Department of Internal Medicine, University of Giessen
Giessen, D-35392, Germany
Related Publications (11)
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. doi: 10.1111/j.1600-6143.2005.01101.x.
PMID: 16303009BACKGROUNDSadeghi 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. doi: 10.1097/01.TP.0000063706.52369.ED.
PMID: 12717229BACKGROUNDStaak 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. doi: 10.1016/j.transproceed.2006.10.041.
PMID: 17175311BACKGROUNDWeimer 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. doi: 10.1016/s0198-8859(00)00152-x.
PMID: 11053632BACKGROUNDWeimer 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. doi: 10.1097/01.TP.0000058808.37349.23.
PMID: 12829918BACKGROUNDWeimer 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. doi: 10.1111/j.1432-2277.2004.00047.x.
PMID: 15691277BACKGROUNDWeimer 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. doi: 10.1111/j.1600-6143.2006.01407.x. Epub 2006 Jun 9.
PMID: 16771810BACKGROUNDDaniel 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-Apr;24(2):281-9. doi: 10.1111/j.1399-0012.2009.01067.x. Epub 2009 Aug 27.
PMID: 19712086BACKGROUNDSusal 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. doi: 10.1097/00007890-200004150-00021.
PMID: 10798750BACKGROUNDSusal 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. doi: 10.1097/01.asn.0000014256.75920.5b.
PMID: 12039995BACKGROUNDWeimer R, Karakizlis H, Renner F, Dietrich H, Daniel V, Susal C, Schuttler C, Kamper D, Leicht D, Worlen M, Milchsack K, Renner L, Stich M, Grone HJ, Hecker A, Horbelt R, Padberg W, Opelz G. Long-term compromised immune regulation after rituximab induction in blood group incompatible (ABOi) living-donor renal transplantation - 5 year results of a prospective pilot study. Front Immunol. 2025 Dec 12;16:1706158. doi: 10.3389/fimmu.2025.1706158. eCollection 2025.
PMID: 41459482DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Rolf Weimer, Prof. Dr.
University of Giessen, Department of Internal Medicine
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- head of renal transplant program, University of Giessen
Study Record Dates
First Submitted
June 2, 2010
First Posted
June 3, 2010
Study Start
January 1, 2010
Primary Completion
June 18, 2019
Study Completion
June 18, 2019
Last Updated
October 8, 2019
Record last verified: 2019-10
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
- Time Frame
- data will be available up to 1year post study completion
- Access Criteria
- seen above
all individual participant data are available to the members of the study group who treat the patients in the Department of Internal Medicine, University Clinic of Giessen (i.e. all participants of the study group working in the Department of Internal Medicine)