Rituximab for Prevention of Rejection After Renal Transplantation

NCT00565331 | Completed Phase 2

• 2 other identifiers: RRT06UMC Radboud RI000131
• Study Type: interventional
• Target: 280
• Locations: 1 country
• Sites: 1

Brief Summary

Our standard immunosuppressive treatment after renal transplantation is a combination of tacrolimus, mycophenolate mofetil, and prednisolone. With this regimen the incidence of acute rejection within the first six months after transplantation has dropped to about 20%. The main challenge at present remains to improve long-term outcome by preventing chronic allograft nephropathy (CAN). Since acute rejection is a strong predictor of CAN, a further decrease in the incidence of acute rejection can improve the long-term graft survival. Current strategies to prevent rejection are mainly directed at alloreactive T cells. Recently, the attention for the role of antibodies in the pathogenesis of acute rejection has increased. In addition, anti-B cell therapy was shown to be effective in diseases that were considered to be mainly T cell driven, like rheumatoid arthritis. In the latter case it has been suggested that anti-B cell antibodies may impair the antigen presenting function of B cells. We therefore decided to investigate the effectiveness and safety of the anti-B cell monoclonal antibody rituximab for prophylaxis of acute rejection after renal transplantation. Study design: Double-blind, placebo controlled intervention study. One group receives a single dose of rituximab of 375 mg/m2 intravenously at the time of transplantation, and the other group receives a placebo infusion. Primary Objective: To determine the incidence and severity of biopsy-confirmed acute rejection within the first six months after transplantation. Secondary Outcomes:

• Renal function as estimated by the endogenous creatinine clearance at 6 months
• Occurrence of chronic allograft nephropathy at 6 months
• Cumulative incidence of infections and malignancies at 6 months
• Medical costs during the first 6 months after transplantation
• Patient and graft survival

Conditions

Kidney Transplantation

Outcome Measures

Primary Outcomes (1)

• Incidence and severity of biopsy-confirmed acute rejection

  First six months after transplantation

Secondary Outcomes (4)

• Renal function as estimated by the endogenous creatinine clearance

  6 months after transplantation

• Occurrence of chronic allograft nephropathy

  First 6 months after transplantation

• Cumulative incidence of infections and malignancies

  First 6 months after transplantation

• Patient and graft survival

  First six months after transplantation

Study Arms (2)

1

ACTIVE COMPARATOR

Rituximab

Drug: Rituximab

2

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Rituximab DRUG

single dose of rituximab of 375 mg/m2 intravenously at the time of transplantation

Also known as: Mabthera, Rituxan

1

Placebo DRUG

saline solution

2

Eligibility Criteria

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

You may qualify if:

• Renal transplant recipients
• Signed, dated, and witnessed IRB approved informed consent

You may not qualify if:

• Pregnancy
• Living donor, who is HLA identical.
• Hemolytic uremic syndrome as original kidney disease.
• Focal segmental glomerulosclerosis that had recurred in a previous graft.
• More than two previously failed grafts and/or PRA \> 85%.
• Previous treatment with anti-CD20 antibodies.
• Diabetes mellitus that is currently not treated with insulin.
• Total white blood cell count \<3,000/mm3 or platelet count \<75,000/mm3.
• Active infection with hepatitis B, hepatitis C, or HIV.
• History of tuberculosis

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Hoffmann-La Roche: collaborator
• Astellas Pharma GmbH: collaborator

Study Sites (1)

Radboud University Nijmegen Medical Centre

Nijmegen, 6500 HB, Netherlands

Location

Related Publications (3)

• Pescovitz MD. Rituximab, an anti-cd20 monoclonal antibody: history and mechanism of action. Am J Transplant. 2006 May;6(5 Pt 1):859-66. doi: 10.1111/j.1600-6143.2006.01288.x.

  PMID: 16611321 BACKGROUND

• Kamburova EG, Koenen HJ, van den Hoogen MW, Baas MC, Joosten I, Hilbrands LB. Longitudinal analysis of T and B cell phenotype and function in renal transplant recipients with or without rituximab induction therapy. PLoS One. 2014 Nov 13;9(11):e112658. doi: 10.1371/journal.pone.0112658. eCollection 2014.

  PMID: 25393622 DERIVED

• Smeekens SP, van den Hoogen MW, Kamburova EG, van de Veerdonk FL, Joosten I, Koenen HJ, Netea MG, Hilbrands LB, Joosten LA. The effects of in vivo B-cell depleting therapy on ex-vivo cytokine production. Transpl Immunol. 2013 Jun;28(4):183-8. doi: 10.1016/j.trim.2013.04.008. Epub 2013 May 4.

  PMID: 23651756 DERIVED

Related Links

• Radboud University Nijmegen Medical Centre

MeSH Terms

Interventions

Rituximab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Luuk Hilbrands, MD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 28, 2007
• First Posted: November 29, 2007
• Study Start: December 1, 2007
• Primary Completion: December 1, 2013
• Study Completion: June 1, 2015
• Last Updated: November 10, 2015

Record last verified: 2015-11

Locations

NL (1)