RituxiMab INDuction in Renal Transplantation

NCT01095172 | Unknown Phase 4 DMC

• 4 other identifiers: RituxiRT2009-017066-23957691199154
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 6

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.

Conditions

Function of Renal Transplant

Keywords

Immunosuppression; Rituximab; B cell

Outcome Measures

Primary Outcomes (1)

• Estimated GFR (calculated using the Cockcroft-Gault formula)

  1 year

Secondary Outcomes (5)

• 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

• Changes in B and T cell repertoire

  1 year

Study Arms (2)

Rituximab

EXPERIMENTAL

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

Drug: Rituximab; Drug: Tacrolimus; Drug: Mycophenylate mofetil; Drug: Hydrocortisone; Drug: Prednisolone

Control group

ACTIVE COMPARATOR

Low dose tacrolimus with mycophenylate mofetil and continued prednisolone

Drug: Tacrolimus; Drug: Mycophenylate mofetil; Drug: Hydrocortisone; Drug: Prednisolone

Interventions

Rituximab DRUG

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

Also known as: Mabthera

Rituximab

Tacrolimus DRUG

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

Also known as: Advagraf, Adoport, Prograf

Control group; Rituximab

Mycophenylate mofetil DRUG

Mycophenylate mofetil 2g/day in divided doses

Also known as: MMF, Cellcept

Control group; Rituximab

Hydrocortisone DRUG

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

Control group; Rituximab

Prednisolone DRUG

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.

Rituximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Guy's and St Thomas' NHS Foundation Trust: lead
• Astellas Pharma Europe Ltd.: collaborator

Study Sites (6)

South West Transplant Centre

Plymouth, Devon, PL6 8DH, United Kingdom

Location

East Kent Hospitals NHS Foundation Trust

Canterbury, Kent, CT1 3NG, United Kingdom

Location

Glasgow Renal and Transplant Unit

Glasgow, G11 6NT, United Kingdom

Location

Guy's and St Thomas' NHS Foundation Trust

London, SE1 9RT, United Kingdom

Location

Central Manchester University Hospitals NHS Foundation Trust

Manchester, M13 9WL, United Kingdom

Location

Sheffield Kidney Institute

Sheffield, S5 7AU, United Kingdom

Location

MeSH Terms

Interventions

Rituximab; Tacrolimus; Mycophenolic Acid; Hydrocortisone; Prednisolone

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Macrolides; Lactones; Organic Chemicals; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids; Pregnadienetriols; Pregnadienes

Study Officials

• Nizam Mamode, MD FRCS(Gen)

  Guy's and St Thomas' NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant Surgeon and Reader in Transplant Surgery

Study Record Dates

• First Submitted: March 26, 2010
• First Posted: March 30, 2010
• Study Start: November 1, 2010
• Primary Completion: October 1, 2020
• Study Completion: October 1, 2022
• Last Updated: July 22, 2020

Record last verified: 2020-07

Locations

GB (6)