Trial of Rituximab Given Pre-Transplant to Sensitised Live Donor Kidney Recipients

Kidney Transplantation Clinical Trial

— RAPTURE  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00371904
• Other study ID #: RAPTURE
• Status: Recruiting
• Phase: Phase 2
• First received: September 1, 2006
• Last updated: May 20, 2008
• Start date: April 2006
• Est. completion date: January 2009

Study information

• Verified date: May 2008
• Source: Hunter and New England Health
• Contact: Paul R Trevillian, MBBS, FRACP
• Phone: +61414417311
• Email: Paul.Trevillian[@]hnehealth.nsw.gov.au
• Is FDA regulated: No
• Health authority: Australia: Human Research Ethics Committee
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 192
• Est. completion date: January 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

1. Subjects, age > 18 years

2. Subjects receiving a single organ renal transplant from a living donor

3. 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.

4. 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):

1. Primary renal transplant lost from acute rejection less than six months prior to randomisation

2. Women of childbearing potential with a positive serum or urine pregnancy test or nursing mothers

3. Subjects with history of malignancy (other than non melanoma skin cancer that has been totally excised with no recurrence for two years)

4. Subjects with known contraindications to treatment with rituximab

5. 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

6. Subjects with a positive ABO crossmatch with donor

7. 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

8. 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

9. Subjects who cannot be followed for the study duration

10. 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:

1. All exclusion criteria as at study entry

2. Positive T- and/or B-cell CDC crossmatch at Day -2

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Kidney Transplantation

Intervention

Drug:
• Rituximab
Single dose (375 mg/m2) of rituximab to be given intravenously (IV) 14 days prior to transplantation
• Standard Care
Standard care

Locations

Country	Name	City	State
Australia	Monash Medical Centre	Clayton	Victoria
Australia	Newcastle Transplant Unit, John Hunter Hospital	Newcastle	New South Wales
Australia	Royal Melbourne Hospital	Parkville	Victoria

Sponsors (9)

Lead Sponsor	Collaborator
Hunter and New England Health	Auckland City Hospital, Melbourne Health, Monash Medical Centre, Princess Alexandra Hospital, Brisbane, Australia, Royal Adelaide Hospital, Royal Perth Hospital, Royal Prince Alfred Hospital, Sydney, Australia, Westmead Hospital

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Biopsy proven antibody mediated rejection		12 months
Secondary	Elimination of donor specific antibodies (DSA)		Day - 2 , 7; Months 1, 3, 6, 9 and 12
Secondary	C4d in biopsies		Day 7; Months 3 and 12
Secondary	Plasma exchanges		Month 12
Secondary	Death		Month 12
Secondary	Treated rejection		Month 12
Secondary	Graft loss		Months 3, 6 and 12
Secondary	Treatment failure		Months 6 and 12
Secondary	Calculation of glomerular filtration rate (GFR)		Months 1 - 12
Secondary	Slope of 1/serum creatinine (Ser. Cr)		Months 6 and 12
Secondary	24-hour U protein		Months 3 and 12
Secondary	Safety		Month 12
Secondary	Cancer and infections		Month 12