Evaluation of the Efficacy of a Treatment by One Single Dose of Rituximab (375mg/m2 ) in the Prevention of the Epstein Barr Virus (EBV) Primary Infection and Post-transplant Lymphoproliferative Disorder in Adult EBV Seronegative Patients Who Received an EBV Seropositive Kidney Allograft

NCT04989491 | Recruiting Phase 4

• 1 other identifier: 7678
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Epstein Barr virus infects over 90% of human population and persists during lifetime. After infecting B lymphocytes, EBV remains latent in memory B cells. In immunocompromised patients, primary infection could lead to an uncontrolled EBV infected B cells proliferation because of impaired T cell specific cytotoxicity. The latent EBV infection is characterized by expression of restricted latent gene products, which drive cell proliferation and progression to PTLD. As a consequence, EBV seronegativity and EBV mismatch are major risk factors for developing PTLD. The investigators reported in a previous work from the French Registry that the incidence of PTLD was multiplied by ten in adult EBV negative kidney transplant recipients. Moreover, even if the event is relatively rare after transplantation, the prognosis is severe with high morbidity and an overall mortality rate around 50%. Nowadays, few and inconsistent data exist regarding beneficial preventing strategies like antiviral therapy, reduction of immunosuppression or immunoglobulin infusion in this high-risk population of EBV negative recipients. Therefore, an efficient and safe preventive treatment is still lacking to decrease PTLD incidence. Rituximab, has been already proposed in stem cell transplant recipients as a preemptive therapy in patients with a persistent EBV viremia independently of their EBV status. A pilot study was performed in EBV negative kidney transplant recipients but in a very small population. Schachtner60 reported the cases of 5 EBV negative recipients receiving kidney from EBV positive donors after a treatment with Rituximab. Only 2 patients showed a seroconversion and no patients developed neither a viremia nor a PTLD after 49 months of follow-up. The main objective of the investigators study is to evaluate the efficacy of early infusion of Rituximab in the prevention of EBV primary infection and post-transplant lymphoproliferative disorder (PTLD) occurrence in adult EBV negative kidney transplant recipients transplanted with an EBV positive donor.

Conditions

Epstein-Barr Virus Infections

Outcome Measures

Primary Outcomes (1)

• Primary EBV infection

  Infection assessed by a positive blood EBV viral load and/or EBV seroconversion and/or occurrence of a post-transplant lymphoproliferative disorder

  1 year post-transplantation

Study Arms (2)

Experimental group

EXPERIMENTAL

Prophylactic treatment with Rituximab: one single dose of 375mg/m2 intravenous 7 days before transplantation in case of living donor or at time of transplantation (D0 or D1) in case of transplantation with a deceased donor.

Drug: Rituximab

control group

ACTIVE COMPARATOR

Immunosuppression treatment will be given according to the practice of the centers; use of Thymoglobuline is strongly discouraged because of EBV seronegativity and risk of lymphoma. Basiliximab is recommended for induction therapy. Recommended maintenance immunosuppression consists in a calcineurin inhibitor (tacrolimus or ciclosporine), MMF and Steroids

Other: control group

Interventions

Rituximab DRUG

One single dose of rituximab intravenously (IV)

Experimental group

control group OTHER

No treatment

control group

Eligibility Criteria

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

You may qualify if:

• Adult patients (age ≥18 years at transplantation)
• Kidney and kidney pancreas simultaneous transplantation
• EBV seronegative patients (IgG anti EBNA, IgG anti VCA and IgM anti VCA negative) (from 6 months before transplantation to the day of transplantation, included)
• Patient who have given written informed consent
• Negative pregnancy test and use of contraception during all the study
• EBV positive donor
• Patient affiliated to a social security scheme

You may not qualify if:

• Patient with known HBV active infection
• Allergy to Rituximab
• Severe Immune deficiency
• Severe cardiac insufficiency
• Pregnant or lactating women
• Women of child bearing potential unless they are using a birth control method
• Patient under judicial protection or under guardianship
• Any form of substance abuse, psychiatric disorder or condition, which, in the opinion of the investigator, is incompatible with the participation in the study
• Unlikely to comply with the visits scheduled in the protocol.

Sponsors & Collaborators

• University Hospital, Strasbourg, France: lead

Study Sites (1)

Les Hôpitaux Universitaires de Strasbourg

Strasbourg, 67000, France

RECRUITING

MeSH Terms

Conditions

Epstein-Barr Virus Infections

Interventions

Rituximab; Control Groups

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods

Central Study Contacts

Sophie Ohlmann-Caillard

CONTACT

0369550511; sophie.caillard@chru-strasboourg.fr

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2021
• First Posted: August 4, 2021
• Study Start: December 1, 2021
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: August 19, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)