ReMIND: RituxiMab INDuction in Renal Transplantation

Sponsor

Guy's and St Thomas' NHS Foundation Trust (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT01095172

Collaborator

Astellas Pharma Europe Ltd. (Industry)

100

Enrollment

Locations

Arms

143

Duration (Months)

16.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Hypothesis:

That B cell depletion, rather than reducing acute rejection, will allow minimisation of immunosuppression, which may lead to better graft survival.

Aim:

To assess whether the addition of rituximab to a low-dose tacrolimus immunosuppression regime allows a reduction in steroid administration.

Objectives:

To assess whether B cell depletion affects graft function, acute rejection and complication rates
To assess whether the T cell response to allotransplantation is impaired by B cell depletion.

Condition or Disease	Intervention/Treatment	Phase
Function of Renal Transplant	Drug: Rituximab Drug: Tacrolimus Drug: Mycophenylate mofetil Drug: Hydrocortisone Drug: Prednisolone Drug: Prednisolone	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized Trial of Rituximab in Induction Therapy for Living Donor Renal Transplantation

Study Start Date :

Nov 1, 2010

Anticipated Primary Completion Date :

Oct 1, 2020

Anticipated Study Completion Date :

Oct 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rituximab Rituximab 375mg/m2 Low dose tacrolimus with mycophenylate mofetil, hydrocortisone and 1 week prednisolone	Drug: Rituximab 375mg/m^2, single dose given 2-4 weeks prior to transplantation Other Names: Mabthera Drug: Tacrolimus dose calculated to give levels of 3-7ng/ml Other Names: Advagraf, Adoport, Prograf Drug: Mycophenylate mofetil Mycophenylate mofetil 2g/day in divided doses Other Names: MMF, Cellcept Drug: Hydrocortisone 100mg hydrocortisone on the evening of the day of surgery and 2 further doses of hydrocortisone on day 1 post transplant. Drug: Prednisolone Prednisolone 0.3mg/kg on day 2, 0.25mg/kg on day 3, 0.2mg/kg on day 4 and 0.16mg/kg on day 5. On day 6 they will receive 5mg prednisolone, and on day 7 none.
Active Comparator: Control group Low dose tacrolimus with mycophenylate mofetil and continued prednisolone	Drug: Tacrolimus dose calculated to give levels of 3-7ng/ml Other Names: Advagraf, Adoport, Prograf Drug: Mycophenylate mofetil Mycophenylate mofetil 2g/day in divided doses Other Names: MMF, Cellcept Drug: Hydrocortisone 100mg hydrocortisone on the evening of the day of surgery and 2 further doses of hydrocortisone on day 1 post transplant. Drug: Prednisolone Reducing dose of prednisolone over at least 6 months. Subsequent steroid maintenance or withdrawal will be at the discretion of the patient's clinician.

Arm

Intervention/Treatment

Experimental: Rituximab

Rituximab 375mg/m2 Low dose tacrolimus with mycophenylate mofetil, hydrocortisone and 1 week prednisolone

Drug: Rituximab

375mg/m^2, single dose given 2-4 weeks prior to transplantation

Other Names:

Mabthera

Drug: Tacrolimus

dose calculated to give levels of 3-7ng/ml

Other Names:

Advagraf, Adoport, Prograf

Drug: Mycophenylate mofetil

Mycophenylate mofetil 2g/day in divided doses

Other Names:

MMF, Cellcept

Drug: Hydrocortisone

100mg hydrocortisone on the evening of the day of surgery and 2 further doses of hydrocortisone on day 1 post transplant.

Drug: Prednisolone

Prednisolone 0.3mg/kg on day 2, 0.25mg/kg on day 3, 0.2mg/kg on day 4 and 0.16mg/kg on day 5. On day 6 they will receive 5mg prednisolone, and on day 7 none.

Active Comparator: Control group

Low dose tacrolimus with mycophenylate mofetil and continued prednisolone

Drug: Tacrolimus

dose calculated to give levels of 3-7ng/ml

Other Names:

Advagraf, Adoport, Prograf

Drug: Mycophenylate mofetil

Mycophenylate mofetil 2g/day in divided doses

Other Names:

MMF, Cellcept

Drug: Hydrocortisone

100mg hydrocortisone on the evening of the day of surgery and 2 further doses of hydrocortisone on day 1 post transplant.

Drug: Prednisolone

Reducing dose of prednisolone over at least 6 months. Subsequent steroid maintenance or withdrawal will be at the discretion of the patient's clinician.

Outcome Measures

Primary Outcome Measures

Estimated GFR (calculated using the Cockcroft-Gault formula) [1 year]

Secondary Outcome Measures

Biopsy proven acute rejection (based on Banff classification) [1, 2, 3, 4, 5 years]
Allograft survival [1, 2, 3, 4, 5 years]
Patient Survival [1, 2, 3, 4, 5 years]
Infection rate [1 year]
New episodes, including (but not restricted to) viral (e.g. CMV, EBV), bacterial (e.g. Urinary Tract Infections with details of causative organism) and fungal infections will be recorded at each assessment time-point.
Changes in B and T cell repertoire [1 year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adult patients over 18 years receiving their first living donor renal transplant, or their second if the first was not lost from acute rejection
Patients who have given written informed consent
Women of child bearing potential taking adequate contraception.

Exclusion Criteria:

Previous other organ transplants lost through acute rejection
Patients undergoing antibody incompatible transplantation
Patients with other organ transplants
Patients previously treated with cyclophosphamide, ATG, OKT3 or rituximab
Patients with white cell count below 4.0x10^9/L.
Patients with platelet count below 100x10^9/L
Patients who are treated with drugs that are strong inhibitors or inducers of cytochrome P450, or treated with terfenadine, astemizole, cisapride or lovastatin
Patients who have been involved in any other investigational trial or non protocol immunosuppressive regimen in the previous 90 days prior to transplant
Pregnant or breastfeeding women
Patients with a documented history of malignancy and its origins and treatment in the last five years. (Localised basal cell carcinoma of the skin is permitted)
Patients known to be HIV, Hepatitis B surface antigen or Hepatitis C antibody positive
Patients who in the opinion of the Investigator would not be a suitable candidate for study participation
Women of child bearing potential not willing to take adequate contraception

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	South West Transplant Centre	Plymouth	Devon	United Kingdom	PL6 8DH
2	East Kent Hospitals NHS Foundation Trust	Canterbury	Kent	United Kingdom	CT1 3NG
3	Glasgow Renal and Transplant Unit	Glasgow		United Kingdom	G11 6NT
4	Guy's and St Thomas' NHS Foundation Trust	London		United Kingdom	SE1 9RT
5	Central Manchester University Hospitals NHS Foundation Trust	Manchester		United Kingdom	M13 9WL
6	Sheffield Kidney Institute	Sheffield		United Kingdom	S5 7AU