Trial of Rituximab Given Pre-Transplant to Sensitised Live Donor Kidney Recipients (RAPTURE)
Recruitment status was Recruiting
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Purpose
About one third of prospective kidney transplant recipients have antibodies in their blood directed against the tissues of their only available kidney donor. Recently, "desensitisation" treatments when administered pre-transplant have allowed successful transplantation of these patients despite high rates of acute antibody mediated rejection (AAMR). The investigators propose to test in a randomised controlled trial whether rituximab, a monoclonal antibody that depletes B-lymphocytes, will safely lower antibody mediated rejection (AMR) rates when added to "standard" therapy. The investigators will also test whether rituximab enables more patients to achieve a negative crossmatch against their donor and thereby allow more transplants to proceed.
| Condition | Intervention | Phase |
|---|---|---|
|
Kidney Transplantation |
Drug: Rituximab Drug: Standard Care |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Prevention |
| Official Title: | A Prospective Open Label Randomised Multicentre Study Evaluating the Efficacy & Safety of Rituximab Given Pre-Transplant to Sensitised Renal Allograft Recipients in Addition to a "Standard" Desensitisation Regimen Consisting of PE/IVIG & MMF |
- Biopsy proven antibody mediated rejection [ Time Frame: 12 months ]
- Elimination of donor specific antibodies (DSA) [ Time Frame: Day - 2 , 7; Months 1, 3, 6, 9 and 12 ]
- C4d in biopsies [ Time Frame: Day 7; Months 3 and 12 ]
- Plasma exchanges [ Time Frame: Month 12 ]
- Death [ Time Frame: Month 12 ]
- Treated rejection [ Time Frame: Month 12 ]
- Graft loss [ Time Frame: Months 3, 6 and 12 ]
- Treatment failure [ Time Frame: Months 6 and 12 ]
- Calculation of glomerular filtration rate (GFR) [ Time Frame: Months 1 - 12 ]
- Slope of 1/serum creatinine (Ser. Cr) [ Time Frame: Months 6 and 12 ]
- 24-hour U protein [ Time Frame: Months 3 and 12 ]
- Safety [ Time Frame: Month 12 ]
- Cancer and infections [ Time Frame: Month 12 ]
| Estimated Enrollment: | 192 |
| Study Start Date: | April 2006 |
| Estimated Study Completion Date: | January 2009 |
| Arms | Assigned Interventions |
|---|---|
| Experimental: 1 |
Drug: Rituximab
Single dose (375 mg/m2) of rituximab to be given intravenously (IV) 14 days prior to transplantation
Other Name: Mabthera
|
| Active Comparator: 2 |
Drug: Standard Care
Standard care
|
Detailed Description:
This study is designed to investigate in a prospective, randomised fashion whether a single intravenous dose of rituximab (375 mg/m2) given two weeks prior to transplant, in addition to standard therapy, will allow sensitised renal transplant subjects to achieve a negative CDC crossmatch and thereby proceed to live donor transplantation. We will also evaluate whether rituximab will reduce the number of AAMR episodes in the post-transplant period, compared to controls. All eligible subjects must have a positive T- and/or B-cell CDC or flow cytometry crossmatch and have donor-specific antibodies identified by solid-phase assay at screening. All subjects will receive a standard desensitisation regimen that includes plasma exchange/IVIG + MMF before and immediately after transplantation followed by a standard care immunosuppressive regimen (IL-2R antagonist, tacrolimus, mycophenolate mofetil [MMF] and corticosteroids) after transplantation.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion criteria:
- Subjects, age > 18 years
- Subjects receiving a single organ renal transplant from a living donor
- Positive T-cell and/or B-cell crossmatch by complement dependent cytotoxicity (CDC) and/or positive flow cytometry crossmatch with confirmed donor-specific antibodies on solid-phase assay at screening. Positive CDC T-cell and/or B-cell crossmatch titre must be less than or equal to 1:64.
- Subjects capable of understanding the purposes and risks of the study and who can give written informed consent
Exclusion Criteria at Study Entry (4 weeks prior to transplant):
- Primary renal transplant lost from acute rejection less than six months prior to randomisation
- Women of childbearing potential with a positive serum or urine pregnancy test or nursing mothers
- Subjects with history of malignancy (other than non melanoma skin cancer that has been totally excised with no recurrence for two years)
- Subjects with known contraindications to treatment with rituximab
- Subjects with haemoglobin < 8.5 g/dL, WBC value of < 3000/mm3 or a platelet count of < 50,000/mm3 that is unlikely to resolve prior to randomisation
- Subjects with a positive ABO crossmatch with donor
- Subjects with severe diarrhoea or other gastrointestinal disorders that might interfere with the ability to absorb oral medication and is unlikely to resolve prior to randomisation
- Subjects participating in another interventional clinical trial or requiring treatment with un-marketed investigational drugs or who would be expected to require other medications prohibited by the protocol
- Subjects who cannot be followed for the study duration
- Subjects with disorders or conditions that may interfere with the ability to comply with study procedures and/or requirements
Additional Exclusion Criteria at Day -2 before Transplantation:
- All exclusion criteria as at study entry
- Positive T- and/or B-cell CDC crossmatch at Day -2
Contacts and Locations| Contact: Paul R Trevillian, MBBS, FRACP | +61414417311 | Paul.Trevillian@hnehealth.nsw.gov.au |
| Contact: Solomon Cohney, MBBS, FRACP, PhD | +61393427159 | Solomon.Cohney@wh.org.au |
| Australia, New South Wales | |
| Newcastle Transplant Unit, John Hunter Hospital | Recruiting |
| Newcastle, New South Wales, Australia, 2305 | |
| Contact: Paul R Trevillian, MBBS, FRACP +61249214326 Paul.Trevillian@hnehealth.nsw.gov.au | |
| Contact: Ann Stein, RN +61249214341 Ann.Stein@hnehealth.nsw.gov.au | |
| Principal Investigator: Paul R Trevillian, MBBS, FRACP | |
| Australia, Victoria | |
| Monash Medical Centre | Not yet recruiting |
| Clayton, Victoria, Australia, 3168 | |
| Contact: John Kanellis, MBBS, PhD, FRACP +61395943070 john.kanellis@med.monash.edu.au | |
| Contact: Janet Andrew +61395943526 j.andrew@southernhealth.org.au | |
| Principal Investigator: John Kanellis, MBBS, PhD, FRACP | |
| Royal Melbourne Hospital | Not yet recruiting |
| Parkville, Victoria, Australia, 3052 | |
| Contact: Shlomo Cohney, MBBS +61393427159 Solomon.Cohney@wh.org.au | |
| Contact: Maria Farrell +61393427077 maria.farrell@mh.org.au | |
| Principal Investigator: Shlomo Cohney, MBBS, PhD, FRACP | |
| Study Chair: | Paul R Trevillian, MBBS, FRACP | Newcastle Transplant Unit, John Hunter Hospital |
| Study Chair: | Solomon Cohney, MBBS, FRACP, PhD | Melbourne Health |
More Information
No publications provided
| ClinicalTrials.gov Identifier: | NCT00371904 History of Changes |
| Other Study ID Numbers: | RAPTURE |
| Study First Received: | September 1, 2006 |
| Last Updated: | May 20, 2008 |
| Health Authority: | Australia: Human Research Ethics Committee |
Keywords provided by Hunter and New England Health:
|
Rituximab donor sensitised antibody rejection |
Additional relevant MeSH terms:
|
Rituximab Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions |
Antirheumatic Agents Therapeutic Uses Antineoplastic Agents |
ClinicalTrials.gov processed this record on May 23, 2013