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Sponsors and Collaborators: |
Imperial College London Medical Research Council Hoffmann-La Roche |
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Information provided by: | Imperial College London |
ClinicalTrials.gov Identifier: | NCT00476164 |
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 and/or proteinuria in patients with C4d+, chronic (humoral) rejection in whom standard therapeutic approaches have failed.
Secondary objective (s);
Study Design; Prospective, randomised, two arm, open-labeled
Study Endpoints; Primary
Sample Size; 15 patients to be randomised to each arm (i.e. 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;
Investigational medicinal product and dosage; Rituximab, 1g on day 0 and 1g on day 14
Active comparator product(s); None
Route(s) 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' and/or 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 and/or 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
Condition | Intervention | Phase |
---|---|---|
Kidney Transplantation Graft Rejection Immunosuppression |
Drug: Rituximab |
Phase IV |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study |
Official Title: | Randomised Trial of Anti-Cd20 in C4d+ Chronic Allograft Nephropathy |
Estimated Enrollment: | 120 |
Study Start Date: | January 2007 |
Ages Eligible for Study: | 18 Years to 70 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contact: Anthony Dorling, PhD, FRCP | +44 2083831707 | a.dorling@imperial.ac.uk |
Contact: Kin Y Shiu, MRCP | +442083831713 | k.shiu@imperial.ac.uk |
United Kingdom | |
Imperial College London and West London Renal & Transplantation Centre | Recruiting |
London, United Kingdom, W12 0NN | |
Principal Investigator: Anthony Dorling, PhD FRCP |
Principal Investigator: | Anthony Dorling | Imperial College London |
Responsible Party: | Imperial College London ( Anthony Dorling ) |
Study ID Numbers: | 2006-002330-38 |
Study First Received: | May 18, 2007 |
Last Updated: | May 9, 2008 |
ClinicalTrials.gov Identifier: | NCT00476164 |
Health Authority: | United Kingdom: Medicines and Healthcare Products Regulatory Agency |
chronic allograft nephropathy C4d Anti-CD20 B cells Antibody |
Antibodies Rituximab Kidney Diseases Immunoglobulins |
Immunologic Factors Antineoplastic Agents Therapeutic Uses |
Physiological Effects of Drugs Antirheumatic Agents Pharmacologic Actions |