Kidney TransplantationPhase 2NCT01136395
Impact of Rituximab (RTx) Induction and Living Donation on Immunoregulation and Virus Control in Renal Transplantation
A Phase 2 study testing Rituximab, living donor transplantation and deceased donor transplantation in people with Kidney Transplantation and Rituximab (RTx), run by University of Giessen at 1 site in Germany.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Kidney Transplantation, Rituximab (RTx), Living Donors
- What is being tested?
- Rituximab, living donor transplantation and deceased donor transplantation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 85 participants
- Where
- 1 siteGermany
- Study dates
- Jan 2010to 18 Jun 2019
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Germany1 site
Department of Internal Medicine, University of Giessen
Giessen, D-35392
About this study
Official title: Impact of Rituximab Induction and Living Donation on Immunoregulation and Virus Control in Renal Transplantation - a Prospective Pilot Study
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.
Read the detailed description
Objective. Blood group incompatible (ABOi) LD renal transplantation represents a recognized treatment modality in Germany. In this setting, ethical considerations allow for a detailed study of short- and long-term immunological and virological effects of Rtx induction therapy, including sequential protocol biopsies. In the proposed project we will perform analyses on peripheral blood, iliac lymph nodes and protocol biopsies. Protocol biopsies are routinely obtained 3 and 12 months posttransplant at the Universities of Giessen and Freiburg. In this prospective, open pilot study, immunological parameters of graft outcome and control of polyomavirus, EBV and CMV replication will be compared between RTx-treated ABOi LD renal transplant recipients (n=25-30, group 1) and blood group compatible LD renal transplant recipients without Rtx induction (n=25-30, group 2) but otherwise comparable immunosuppressive treatment (MPS and Tacr, switch to Tacr-MR (modified release) within 2 weeks posttransplant; follow-up of 5 years). The same analyses will be done in DD renal transplant recipients treated with Tacr (switch to Tacr-ME) and MPS (n=25-30, group 3). This study design allows to analyze the impact of living donation on immunoregulation and virus control (groups 2 versus 3).
Background. There is growing evidence that humoral mechanisms play a major role in chronic allograft dysfunction, which was shown to be significantly associated with de-novo formation of donor-specific antibodies against human leucocyte antigens (HLA). However, B cells appear to act not only in humoral responses against the graft but may play a significant role in T-cell mediated antidonor responses due to their role as effective antigen-presenting cells. This is further suggested by the fact that Rtx is effective in primarily T-cell mediated diseases such as rheumatoid arthritis or multiple sclerosis.
Hypothesis/specific aims. We hypothesize that Rtx induction may alter immunoregulation short- and long-term after renal transplantation with the potential to improve long-term outcome. Graft protective effects of Rtx induction may be provided by B cell depletion and the resulting effects on humoral as well as T cell responses, and also by altered responses after B cell repopulation. Possible negative effects of Rtx on polyomavirus and CMV control as well as protective effects on EBV replication, de-novo monoclonal gammopathy and regulation of lymphoma growth factors (interleukins 6 and 10 (IL-6, IL-10)) will be analyzed. Furthermore, B cell subset analysis in peripheral blood and the probably associated impact of Rtx on B cell depletion in graft draining iliac lymph nodes may enable us to establish an optimized Rtx dosage and thereby allow successful ABOi renal transplantation without the currently observed 15% drop outs.
Preliminary results. We have performed clinical studies showing the predictive power of immune parameters such as regulatory anti-Fab autoantibodies, sCD30, CD4 (cluster of differentiation 4) helper activity, and CD4 cell IL-4 (interleukin 4) and IL-10 (interleukin 10) responses on graft outcome. The long-term effect of Rtx induction therapy and of living donation on these parameters will be analyzed.
Previously, we found that patients at risk of polyomavirus nephropathy may be recognized early posttransplant by sequential reverse transcriptase polymerase chain (rt-PCR) assessment of polyomavirus replication in urine. Sequential rt-PCR testing of polyomavirus replication in urine and plasma will be used to analyze effects of Rtx induction on polyomavirus control.
Proposed methods. Immune parameters will be analyzed mainly pretransplant, 3 months and 1, 2 and 5 years posttransplant. Flow cytometry (including regulatory T cells, B cell subsets, expression of cytokine receptors, costimulatory and adhesion molecules), mitogen-stimulated allogeneic cocultures, protein-A plaque assay (B cell responses, CD4 helper activity), intracellular cytokine analysis of CD4+ and CD8+ (cluster of differentiation 8) T cells, B cells and monocytes, rt-PCR for virological studies (BKV, JCV, CMV, EBV) and immunofluorescent staining of iliac lymph nodes (obtained at time of transplantation) and protocol biopsies will be used. Donor-specific antibodies will be detected using lymphocytotoxicity, HLA class I and II ELISA and Luminex assays. Donor-specificity will be confirmed by T- and B-cell crossmatch with donor cells. Regulatory IgG (immunoglobulin G) and IgA (immunoglobulin A) anti-Fab autoantibodies, neopterin and sCD30 will be assessed by ELISA.
Expected results. We expect that Rtx induction will show an impact on immunological parameters of graft outcome, such as de-novo posttransplant antidonor HLA antibody formation. This pilot study may allow for improved long-term kidney graft outcome in recipients with immunologic risk parameters by virtue of patient-tailored immunosuppressive therapy. In ABOi renal transplantation, this study may prevent the current 15% drop out rates by allowing an optimized Rtx dosage based on the intended dose response analysis (B cell subset analysis in blood and graft draining lymph nodes). Furthermore, this study will allow risk estimation of Rtx administration with respect to CMV and polyomavirus replication, and may provide clues concerning protection against EBV replication and posttransplant lymphoproliferative disease. The latter point is of great clinical importance in patients with an enhanced PTLD (posttransplant lymphoproliferative disease) risk such as EBV negative recipients of EBV positive grafts.
- Conditions
- Kidney Transplantation, Rituximab (RTx), Living Donors, Immunology, Virus
- Being tested
- Rituximab, living donor transplantation, deceased donor transplantation
- Keywords
- Kidney Transplantation, Rituximab, Living Donor, ABO Incompatible (ABOi) Transplantation, Immunology, Cytomegalovirus (CMV), Epstein Barr virus (EBV), Polyomavirus
- Medical subject headings
- Virus Diseases, Epstein-Barr Virus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
Also called Blood group incompatible (ABOi) living donor (LD) renal transplantation, Anti-CD20 (cluster of differentiation 20) Monoclonal Antibody (MoAb)
375mg/m2 4 weeks before ABOi LD transplantation
living donor transplantationProcedure or surgery
Also called Blood group compatible (ABOc) LD NTx
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 transplantationProcedure or surgery
Also called Deceased donor (DD) renal 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 virus (BKV), JC virus (JCV)), respectively
| Study group | Role | What they receive |
|---|---|---|
| LD kidney transplantation, ABOi | Active comparator | Living donor (LD) kidney transplantation, ABO incompatible (ABOi); Immunosuppressive treatment: Tacrolimus (Tacr)/ Mycophenolate sodium (MPS), Basiliximab induction, Rtx induction Receives: Drug: Rituximab; Procedure: living donor transplantation |
| LD kidney transplantation, ABOc | Active comparator | Living donor (LD) kidney transplantation, ABO compatible (ABOc); Immunosuppressive treatment: Tacr/MPS, Basiliximab induction Receives: Procedure: living donor transplantation |
| DD kidney transplantation | Active comparator | Deceased donor (DD) kidney transplantation, ABO compatible; Immunosuppressive treatment: Tacr/MPS, Basiliximab induction Receives: Procedure: deceased donor transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Impact of Rtx on immune parameters predictive of graft outcome including B cell responses
immune parameters of graft outcome: see "detailed description"
Measured: 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"
Measured: 5 years posttransplant
Impact of Rtx on virus replication
outcome measure description: EBV PCR (in blood)
Measured: 5 years posttransplant
Impact of Rtx on virus replication
outcome measure description: CMV PCR (in blood)
Measured: 5 years posttransplant
Impact of Rtx on virus replication
outcome measure description: BKV PCR (in blood)
Measured: 5 years posttransplant
Impact of Rtx on virus replication
outcome measure description: BKV PCR (in urine)
Measured: 5 years posttransplant
Impact of Rtx on virus replication
outcome measure description: JCV PCR (in blood)
Measured: 5 years posttransplant
Impact of Rtx on virus replication
outcome measure description: JCV PCR (in urine)
Measured: 5 years posttransplant
Impact of living donation on virus replication
outcome measure description: EBV PCR (in blood)
Measured: 5 years posttransplant
Impact of living donation on virus replication
outcome measure description: CMV PCR (in blood)
Measured: 5 years posttransplant
Impact of living donation on virus replication
outcome measure description: BKV PCR (in blood)
Measured: 5 years posttransplant
Impact of living donation on virus replication
outcome measure description: BKV PCR (in urine)
Measured: 5 years posttransplant
Impact of living donation on virus replication
outcome measure description: JCV PCR (in blood)
Measured: 5 years posttransplant
Impact of living donation on virus replication
outcome measure description: JCV PCR (in urine)
Measured: 5 years posttransplant
Secondary outcomes (13)
Patient survival
patient survival 5 years posttransplant will be analyzed
Measured: 5 years posttransplant
Graft survival
Graft survival 5 years posttransplant will be analyzed
Measured: 5 years posttransplant
Graft function and proteinuria
5-year graft function will be analyzed by serum creatinine and measured creatinine clearance, proteinuria by proteinuria within a 24h urine collection period
Measured: 5 years posttransplant
Graft function
5-year graft function will be analyzed by serum creatinine and measured creatinine clearance, proteinuria by proteinuria within a 24h urine collection period
Measured: 5 years posttransplant
Graft function
5-year graft function will be analyzed by measured creatinine clearance
Measured: 5 years posttransplant
Proteinuria
5-year proteinuria will be analyzed urine collected 24 hours
Measured: 5 years posttransplant
Incidence of acute rejection
incidence of biopsy proven acute rejection within 1 year posttransplant will be analyzed
Measured: 1 year posttransplant
Incidence of acute rejection
incidence of biopsy proven acute rejection within 2 years posttransplant will be analyzed
Measured: 2 years posttransplant
Incidence of acute rejection
incidence of biopsy proven acute rejection within 5 years posttransplant will be analyzed
Measured: 5 years posttransplant
Incidence of chronic allograft dysfunction
Chronic allograft dysfunction (progressive decline of graft function) will be analyzed at 5 years posttransplant.
Measured: 5 years posttransplant
Incidence of severe infectious disease
severe infectious disease as defined by need for in-hospital treatment
Measured: 5 years posttransplant
Incidence of malignancy
all types of malignancies within 5 years posttransplant will be evaluated
Measured: 5 years posttransplant
Incidence of side effects associated with Rtx
all side effects of Rtx treatment which have been described in literature, will be listed
Measured: 5 years posttransplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2010 (estimated)
- Study startJan 2010
- Primary completion18 Jun 2019
- Study completion18 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Kidney TransplantationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 85 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Giessen
- Sponsor type
- University, hospital or other
- Collaborators
- Heidelberg University, German Cancer Research Center, Astellas Pharma US, Inc., Novartis
- Responsible party
- Principal investigator, Prof. Dr. Rolf Weimer, University of Giessen
- Investigators
- Rolf Weimer, Prof. Dr., Principal investigator, University of Giessen, Department of Internal Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01136395
- Sponsor's protocol ID
- NTx-RTx-LD-001
- Other IDs
- 2009-012198-36, 2009
- Status last verified
- Oct 2019
- First submitted
- 2 Jun 2010
- Last updated
- 8 Oct 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: 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)
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. doi: 10.1111/j.1600-6143.2005.01101.x.
PubMed 16303009Sadeghi 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.
PubMed 12717229Staak 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.
PubMed 17175311Weimer 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.
PubMed 11053632Weimer 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.
PubMed 12829918Weimer 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.
PubMed 15691277Weimer 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.
PubMed 16771810Daniel 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.
PubMed 19712086Susal 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.
PubMed 10798750Susal 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.
PubMed 12039995Weimer 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.
PubMed 41459482
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Rituximab Induction and Living Donation on Immunoregulation and Virus Control in Renal Transplantation - a Prospective Pilot Study
- ClinicalTrials.gov ID
- NCT01136395
- Acronym / sponsor ID
- NTx-RTx-LD-001
- Conditions
- Kidney Transplantation, Rituximab (RTx), Living Donors, Immunology, Virus
- Keywords
- Kidney Transplantation, Rituximab, Living Donor, ABO Incompatible (ABOi) Transplantation, Immunology, Cytomegalovirus (CMV), Epstein Barr virus (EBV), Polyomavirus
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 85 participants (actual)
- Lead sponsor
- University of GiessenUniversity, hospital or other
- Collaborators
- Heidelberg University, German Cancer Research Center, Astellas Pharma US, Inc., Novartis
- Study start
- Jan 2010 (actual)
- Primary completion
- 18 Jun 2019 (actual)
- Study completion
- 18 Jun 2019 (actual)
- First posted
- 3 Jun 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Objective. Blood group incompatible (ABOi) LD renal transplantation represents a recognized treatment modality in Germany. In this setting, ethical considerations allow for a detailed study of short- and long-term immunological and virological effects of Rtx induction therapy, including sequential protocol biopsies. In the proposed project we will perform analyses on peripheral blood, iliac lymph nodes and protocol biopsies. Protocol biopsies are routinely obtained 3 and 12 months posttransplant at the Universities of Giessen and Freiburg. In this prospective, open pilot study, immunological parameters of graft outcome and control of polyomavirus, EBV and CMV replication will be compared between RTx-treated ABOi LD renal transplant recipients (n=25-30, group 1) and blood group compatible LD renal transplant recipients without Rtx induction (n=25-30, group 2) but otherwise comparable immunosuppressive treatment (MPS and Tacr, switch to Tacr-MR (modified release) within 2 weeks posttransplant; follow-up of 5 years). The same analyses will be done in DD renal transplant recipients treated with Tacr (switch to Tacr-ME) and MPS (n=25-30, group 3). This study design allows to analyze the impact of living donation on immunoregulation and virus control (groups 2 versus 3).
Background. There is growing evidence that humoral mechanisms play a major role in chronic allograft dysfunction, which was shown to be significantly associated with de-novo formation of donor-specific antibodies against human leucocyte antigens (HLA). However, B cells appear to act not only in humoral responses against the graft but may play a significant role in T-cell mediated antidonor responses due to their role as effective antigen-presenting cells. This is further suggested by the fact that Rtx is effective in primarily T-cell mediated diseases such as rheumatoid arthritis or multiple sclerosis.
Hypothesis/specific aims. We hypothesize that Rtx induction may alter immunoregulation short- and long-term after renal transplantation with the potential to improve long-term outcome. Graft protective effects of Rtx induction may be provided by B cell depletion and the resulting effects on humoral as well as T cell responses, and also by altered responses after B cell repopulation. Possible negative effects of Rtx on polyomavirus and CMV control as well as protective effects on EBV replication, de-novo monoclonal gammopathy and regulation of lymphoma growth factors (interleukins 6 and 10 (IL-6, IL-10)) will be analyzed. Furthermore, B cell subset analysis in peripheral blood and the probably associated impact of Rtx on B cell depletion in graft draining iliac lymph nodes may enable us to establish an optimized Rtx dosage and thereby allow successful ABOi renal transplantation without the currently observed 15% drop outs.
Preliminary results. We have performed clinical studies showing the predictive power of immune parameters such as regulatory anti-Fab autoantibodies, sCD30, CD4 (cluster of differentiation 4) helper activity, and CD4 cell IL-4 (interleukin 4) and IL-10 (interleukin 10) responses on graft outcome. The long-term effect of Rtx induction therapy and of living donation on these parameters will be analyzed.
Previously, we found that patients at risk of polyomavirus nephropathy may be recognized early posttransplant by sequential reverse transcriptase polymerase chain (rt-PCR) assessment of polyomavirus replication in urine. Sequential rt-PCR testing of polyomavirus replication in urine and plasma will be used to analyze effects of Rtx induction on polyomavirus control.
Proposed methods. Immune parameters will be analyzed mainly pretransplant, 3 months and 1, 2 and 5 years posttransplant. Flow cytometry (including regulatory T cells, B cell subsets, expression of cytokine receptors, costimulatory and adhesion molecules), mitogen-stimulated allogeneic cocultures, protein-A plaque assay (B cell responses, CD4 helper activity), intracellular cytokine analysis of CD4+ and CD8+ (cluster of differentiation 8) T cells, B cells and monocytes, rt-PCR for virological studies (BKV, JCV, CMV, EBV) and immunofluorescent staining of iliac lymph nodes (obtained at time of transplantation) and protocol biopsies will be used. Donor-specific antibodies will be detected using lymphocytotoxicity, HLA class I and II ELISA and Luminex assays. Donor-specificity will be confirmed by T- and B-cell crossmatch with donor cells. Regulatory IgG (immunoglobulin G) and IgA (immunoglobulin A) anti-Fab autoantibodies, neopterin and sCD30 will be assessed by ELISA.
Expected results. We expect that Rtx induction will show an impact on immunological parameters of graft outcome, such as de-novo posttransplant antidonor HLA antibody formation. This pilot study may allow for improved long-term kidney graft outcome in recipients with immunologic risk parameters by virtue of patient-tailored immunosuppressive therapy. In ABOi renal transplantation, this study may prevent the current 15% drop out rates by allowing an optimized Rtx dosage based on the intended dose response analysis (B cell subset analysis in blood and graft draining lymph nodes). Furthermore, this study will allow risk estimation of Rtx administration with respect to CMV and polyomavirus replication, and may provide clues concerning protection against EBV replication and posttransplant lymphoproliferative disease. The latter point is of great clinical importance in patients with an enhanced PTLD (posttransplant lymphoproliferative disease) risk such as EBV negative recipients of EBV positive grafts.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| LD kidney transplantation, ABOi | Active comparator | Drug: Rituximab, Procedure: living donor transplantationLiving donor (LD) kidney transplantation, ABO incompatible (ABOi); Immunosuppressive treatment: Tacrolimus (Tacr)/ Mycophenolate sodium (MPS), Basiliximab induction, Rtx induction |
| LD kidney transplantation, ABOc | Active comparator | Procedure: living donor transplantationLiving donor (LD) kidney transplantation, ABO compatible (ABOc); Immunosuppressive treatment: Tacr/MPS, Basiliximab induction |
| DD kidney transplantation | Active comparator | Procedure: deceased donor transplantationDeceased donor (DD) kidney transplantation, ABO compatible; Immunosuppressive treatment: Tacr/MPS, Basiliximab induction |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RituximabAlso: Blood group incompatible (ABOi) living donor (LD) renal transplantation, Anti-CD20 (cluster of differentiation 20) Monoclonal Antibody (MoAb)375mg/m2 4 weeks before ABOi LD transplantation | Drug | LD kidney transplantation, ABOi |
| living donor transplantationAlso: Blood group compatible (ABOc) LD NTxliving 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 | Procedure or surgery | LD kidney transplantation, ABOc, LD kidney transplantation, ABOi |
| deceased donor transplantationAlso: Deceased donor (DD) renal transplantationdeceased 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 | Procedure or surgery | DD kidney transplantation |
Primary outcome
Impact of Rtx on immune parameters predictive of graft outcome including B cell responses
Time frame: 5 years posttransplant
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
parameters of graft outcome: see "detailed description"
Impact of Rtx on virus replication
Time frame: 5 years posttransplant
outcome measure description: EBV PCR (in blood)
Impact of Rtx on virus replication
Time frame: 5 years posttransplant
outcome measure description: CMV PCR (in blood)
Impact of Rtx on virus replication
Time frame: 5 years posttransplant
outcome measure description: BKV PCR (in blood)
Impact of Rtx on virus replication
Time frame: 5 years posttransplant
outcome measure description: BKV PCR (in urine)
Impact of Rtx on virus replication
Time frame: 5 years posttransplant
outcome measure description: JCV PCR (in blood)
Impact of Rtx on virus replication
Time frame: 5 years posttransplant
outcome measure description: JCV PCR (in urine)
Impact of living donation on virus replication
Time frame: 5 years posttransplant
outcome measure description: EBV PCR (in blood)
Impact of living donation on virus replication
Time frame: 5 years posttransplant
outcome measure description: CMV PCR (in blood)
Impact of living donation on virus replication
Time frame: 5 years posttransplant
outcome measure description: BKV PCR (in blood)
Impact of living donation on virus replication
Time frame: 5 years posttransplant
outcome measure description: BKV PCR (in urine)
Impact of living donation on virus replication
Time frame: 5 years posttransplant
outcome measure description: JCV PCR (in blood)
Impact of living donation on virus replication
Time frame: 5 years posttransplant
outcome measure description: JCV PCR (in urine)
13 secondary outcomes
Patient survival
Time frame: 5 years posttransplant
Graft survival
Time frame: 5 years posttransplant
Graft function and proteinuria
Time frame: 5 years posttransplant
Graft function
Time frame: 5 years posttransplant
Graft function
Time frame: 5 years posttransplant
Proteinuria
Time frame: 5 years posttransplant
Incidence of acute rejection
Time frame: 1 year posttransplant
Incidence of acute rejection
Time frame: 2 years posttransplant
Incidence of acute rejection
Time frame: 5 years posttransplant
Incidence of chronic allograft dysfunction
Time frame: 5 years posttransplant
Incidence of severe infectious disease
Time frame: 5 years posttransplant
Incidence of malignancy
Time frame: 5 years posttransplant
Incidence of side effects associated with Rtx
Time frame: 5 years posttransplant
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2019.
- Background: PubMed 16303009Hackstein 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.
- Background: PubMed 12717229Sadeghi 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.
- Background: PubMed 17175311Staak 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.
- Background: PubMed 11053632Weimer 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.
- Background: PubMed 12829918Weimer 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.
- Background: PubMed 15691277Weimer 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.
- Background: PubMed 16771810Weimer 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.
- Background: PubMed 19712086Daniel 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.
- Background: PubMed 10798750Susal 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.
- Background: PubMed 12039995Susal 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.
- Derived from this study: PubMed 41459482Weimer 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.
- Individual participant dataSharing planned: Yes. 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)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rolf Weimer, Prof. Dr. principal investigator
University of Giessen, Department of Internal Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Rituximab, living donor transplantation and deceased donor transplantation in people with Kidney Transplantation and Rituximab (RTx), run by University of Giessen at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Impact of Rtx on immune parameters predictive of graft outcome including B cell responses (time frame: 5 years posttransplant). The study lists 14 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01136395, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2019.