RituxiMab INDuction in Renal Transplantation (ReMIND)

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

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.

Study Overview

• Status: Unknown
• Conditions: Function of Renal Transplant
• Intervention / Treatment: Drug: Rituximab; Drug: Tacrolimus; Drug: Mycophenylate mofetil; Drug: Hydrocortisone; Drug: Prednisolone; Drug: Prednisolone

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 4

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / 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.; 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.
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; 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.; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Estimated GFR (calculated using the Cockcroft-Gault formula)	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	1 year
Changes in B and T cell repertoire		1 year

Collaborators and Investigators

• Sponsor: Guy's and St Thomas' NHS Foundation Trust
• Collaborators: Astellas Pharma Europe Ltd.
• Investigators: Principal Investigator: Nizam Mamode, MD FRCS(Gen), Guy's and St Thomas' NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (ANTICIPATED): October 1, 2020
• Study Completion (ANTICIPATED): October 1, 2022

Study Registration Dates

• First Submitted: March 26, 2010
• First Submitted That Met QC Criteria: March 29, 2010
• First Posted (ESTIMATE): March 30, 2010

Study Record Updates

• Last Update Posted (ACTUAL): July 22, 2020
• Last Update Submitted That Met QC Criteria: July 21, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Immunosuppression; Rituximab; B cell
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Antineoplastic Agents, Immunological; Calcineurin Inhibitors; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Rituximab; Tacrolimus; Hydrocortisone
• Other Study ID Numbers: RituxiRT; 2009-017066-23 (EUDRACT_NUMBER); 95769119 (REGISTRY: ISRCTN); 9154 (REGISTRY: UK Clinical Research Network (CRN) Portfolio)