Renal Transplant Rejection - chronic MedDRA version: 14.1 Level: PT Classification code 10023439 Term: Kidney transplant rejection System Organ Class: 10021428 - Immune system disorders
Conditions
Interventions
Trade Name: MabThera
Product Name: N/A
Product Code: N/A
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN:
Sponsors
King's College London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: To be included in the study the patient must have: •A functioning kidney allograft (with estimated GFR by MDRD >20) and be >6/12 post-transplantation •Either deteriorating allograft function as defined by linear regression of reciprocal creatinine plot. Deterioration will be defined as a negative slope over at least the preceding 3 months (with at least 6 creatinines included) with an adjusted r2 >0.35 and a p value of =0.05 compared to horizontal baseline. Deterioration will be confirmed by Cockcroft Gault eGFR somparisons over same period to rule out body mass as a cause of change in creatinines OR Significant proteinuria defined as a urine protein : creatinine ratio =50 OR Both deteriorating function and proteinuria •CAN, by Banff ’97 criteria, or transplant glomerulopathy on renal allograft biopsy performed within 3/12 of enrolment •Diffuse, linear C4d deposition on at least 25% of peritubular capillary (PTC) and/or glomerular EC of renal transplant biopsy when assessed by immunoperoxidase OR >50% of PTC (alone) when assessed by immunofluorescence. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: The presence of any of the following will preclude patient inclusion •<18 years of age •suspicion of pregnancy confirmed by positive HCG pregnancy test •untreated ureteric obstruction on ultrasound of allograft •history of acute allograft rejection in preceding 3/12 •history of MI in preceding 3/12 •history of malignancy in previous 5 years (excluding tumours limited to skin) •symptomatic IHD •recipient of simultaneous pancreas/kidney transplant •recipient of ABO-incompatible kidney •recipient who underwent an HLA desensitisation procedure prior to transplantation •evidence, on examination of renal allograft biopsy specimen, of recurrent or de-novo disease (except IgA deposition in absence of mesangial proliferation) • evidence, on examination of renal allograft biopsy specimen, of CNI toxicity IF ACCOMPANIED by mostly supra-therapeutic CNI trough levels in the 6 month period preceding biopsy. • doumented allergy to mouse or chimeric human/mouse proteins • HepBsAg+, HCV Ab+ or HIV+ or HepBcAb+ • administration of lymphocyte depleting antibody within 3 months of enrolment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine whether anti-CD20 therapy can stabilise or improve renal function and/or proteinuria in patients with C4d+, chronic (humoral) rejection in whom standard therapeutic approaches have failed. ; Secondary Objective: 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 ; Primary end point(s): •Rate of deterioration in renal function, defined by slope of reciprocal creatinine plot, on samples taken in the preceding 3 months. •Change in degree of proteinuria, where present ;Timepoint(s) of evaluation of this end point: Determined 3-5 months post-randomisation | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(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 ;Timepoint(s) of evaluation of this end point: Secondary endpoints will be determined at 3-5 months post-randomisation and at 1, 2 and 3 years post-recruitment | — |
Countries
United Kingdom
Contacts
Public ContactJoint Clinical Trials Office
Kings College London
Outcome results
None listed