Ignite Creation Date:
2024-05-05 @ 5:31 PM
Last Modification Date:
2024-10-26 @ 9:33 AM
Study NCT ID:
NCT00476164
Status:
COMPLETED
Last Update Posted:
2020-03-05
First Post:
2007-05-18
Brief Title:
Study of Rituximab to Treat Chronic Renal Transplant Rejection
Sponsor:
Kings College London
Organization:
Kings College London
Study Overview
Official Title:
Randomised Trial of Anti-Cd20 in C4d Chronic Allograft Nephropathy
Status:
COMPLETED
Status Verified Date:
2020-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
RituxiCAN-C4
Brief Summary:
Purpose of clinical trial Evaluate the effectiveness of rituximab in C4d CAN
Primary objective To determine whether anti-CD20 therapy can stabilize or improve renal function andor proteinuria in patients with C4d chronic humoral rejection in whom standard therapeutic approaches have failed
Secondary objective s
To compare patient and graft survival between control and rituximab-treated groups
To evaluate the adverse effect profile of rituximab in this group
To correlate changes in circulating B cell numbers anti-HLA and non-HLA Ab profiles and titre with responses to standard therapy and or rituximab
To correlate changes in T cell responsiveness to alloantigens with responses to standard therapy and or rituximab
Study Design Prospective randomised two arm open-labeled
Study Endpoints Primary
Rate of deterioration in renal function defined by slope of reciprocal creatinine plot on samples taken 3-5 months post-randomisation
Change in degree of proteinuria where present at 3-5 months post-randomisation 2 endpoints determined at 3-5 months post-randomisation and at 1 2 and 3 years post-recruitment are
Rate of deterioration in renal function defined by slope of reciprocal creatinine plot determined by analysis of samples taken since previous assessment
Patient survival
Graft survival
Incidence of culture positive infection
Incidence of malignancy
Degree of proteinuria
Changes in circulating CD20 cells in peripheral blood
Changes in anti-graft Ab titres measured every 3 months
Changes in T cell responsiveness to alloantigens measured every 3 months
Sample Size 15 patients to be randomised to each arm ie 30 patients randomised Up to 120 patients will need to be enrolled into the study In addition in those participants that received a living donor kidney these donors will be approached to provide up to 5 samples of blood to help with the in vitro analyses
Summary of eligibility criteria
Male or female renal allograft recipients 18-70 years of age
more than 612 post-transplantation
Either deteriorating allograft function on reciprocal creatinine plot or significant proteinuria or both
C4d- CAN on renal allograft biopsy
Investigational medicinal product and dosage Rituximab 1g on day 0 and 1g on day 14
Active comparator products None
Routes of administration Intravenous infusion
Maximum duration of treatment of a subject 14 days with rituximab The treatment arms of the study including optimisation period formal run-in and post-randomisation phase lasts for 10 months post-recruitment
Procedures Screening enrollment Potentially eligible patients will be identified by screening renal allograft biopsies performed for creeping creatinine andor proteinuria Recruitment by informed consent prior to enrollment
Procedures Baseline In addition to routine tests blood for anti-HLA and non-HLA antibody analysis and for peripheral blood mononuclear cell PBMC purification
Procedures Treatment period 3 month run-in period on optimal conventional immunosuppressive therapy preceded by up to 2 months to allow tailored-optimization Patients will be reviewed at least six times in their normal transplant clinic appointments for routine blood biochemistry full blood count and urine analysis At the end of the run-in period further blood will be taken for anti-graft antibody analysis and PBMC purification Those patients in whom allograft function stabilises andor proteinuria improves will have normal transplant clinic follow-up appointments and have blood taken for further anti-graft antibody and PBMC purification up to every 3 months for 3 years Those with continued deterioration in either allograft function or persisting or worsening proteinuria will be randomised These patients will be reviewed during their normal transplant clinic appointments until the primary end-point and will need to have at least 6 routine blood biochemistry full blood count and urine analysis during the final 3 months of this period post-randomisation At the primary end-point further blood will be taken for anti-graft antibody analysis and PBMC
Procedures End of Study Follow up will continue for 3 years with blood taken for anti-graft antibody analysis and PBMC purification every three months
Procedures for safety monitoring during trial Regular patient interviews and examination routine haematological and biochemical analyses Serious adverse events will be reported and forwarded to the sponsor MHRA LREC and Roche as appropriate The WLRATC transplant research committee will discuss the trial and any safety concerns at their regular three monthly meetings Data will be reviewed after 30 and also after 60 people have been enrolled
Criteria for withdrawal of patients on safety grounds Serious adverse effects related to rituximab infusion
Primary objective To determine whether anti-CD20 therapy can stabilize or improve renal function andor proteinuria in patients with C4d chronic humoral rejection in whom standard therapeutic approaches have failed
Secondary objective s
To compare patient and graft survival between control and rituximab-treated groups
To evaluate the adverse effect profile of rituximab in this group
To correlate changes in circulating B cell numbers anti-HLA and non-HLA Ab profiles and titre with responses to standard therapy and or rituximab
To correlate changes in T cell responsiveness to alloantigens with responses to standard therapy and or rituximab
Study Design Prospective randomised two arm open-labeled
Study Endpoints Primary
Rate of deterioration in renal function defined by slope of reciprocal creatinine plot on samples taken 3-5 months post-randomisation
Change in degree of proteinuria where present at 3-5 months post-randomisation 2 endpoints determined at 3-5 months post-randomisation and at 1 2 and 3 years post-recruitment are
Rate of deterioration in renal function defined by slope of reciprocal creatinine plot determined by analysis of samples taken since previous assessment
Patient survival
Graft survival
Incidence of culture positive infection
Incidence of malignancy
Degree of proteinuria
Changes in circulating CD20 cells in peripheral blood
Changes in anti-graft Ab titres measured every 3 months
Changes in T cell responsiveness to alloantigens measured every 3 months
Sample Size 15 patients to be randomised to each arm ie 30 patients randomised Up to 120 patients will need to be enrolled into the study In addition in those participants that received a living donor kidney these donors will be approached to provide up to 5 samples of blood to help with the in vitro analyses
Summary of eligibility criteria
Male or female renal allograft recipients 18-70 years of age
more than 612 post-transplantation
Either deteriorating allograft function on reciprocal creatinine plot or significant proteinuria or both
C4d- CAN on renal allograft biopsy
Investigational medicinal product and dosage Rituximab 1g on day 0 and 1g on day 14
Active comparator products None
Routes of administration Intravenous infusion
Maximum duration of treatment of a subject 14 days with rituximab The treatment arms of the study including optimisation period formal run-in and post-randomisation phase lasts for 10 months post-recruitment
Procedures Screening enrollment Potentially eligible patients will be identified by screening renal allograft biopsies performed for creeping creatinine andor proteinuria Recruitment by informed consent prior to enrollment
Procedures Baseline In addition to routine tests blood for anti-HLA and non-HLA antibody analysis and for peripheral blood mononuclear cell PBMC purification
Procedures Treatment period 3 month run-in period on optimal conventional immunosuppressive therapy preceded by up to 2 months to allow tailored-optimization Patients will be reviewed at least six times in their normal transplant clinic appointments for routine blood biochemistry full blood count and urine analysis At the end of the run-in period further blood will be taken for anti-graft antibody analysis and PBMC purification Those patients in whom allograft function stabilises andor proteinuria improves will have normal transplant clinic follow-up appointments and have blood taken for further anti-graft antibody and PBMC purification up to every 3 months for 3 years Those with continued deterioration in either allograft function or persisting or worsening proteinuria will be randomised These patients will be reviewed during their normal transplant clinic appointments until the primary end-point and will need to have at least 6 routine blood biochemistry full blood count and urine analysis during the final 3 months of this period post-randomisation At the primary end-point further blood will be taken for anti-graft antibody analysis and PBMC
Procedures End of Study Follow up will continue for 3 years with blood taken for anti-graft antibody analysis and PBMC purification every three months
Procedures for safety monitoring during trial Regular patient interviews and examination routine haematological and biochemical analyses Serious adverse events will be reported and forwarded to the sponsor MHRA LREC and Roche as appropriate The WLRATC transplant research committee will discuss the trial and any safety concerns at their regular three monthly meetings Data will be reviewed after 30 and also after 60 people have been enrolled
Criteria for withdrawal of patients on safety grounds Serious adverse effects related to rituximab infusion
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None