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

Sponsor
University Hospital, Strasbourg, France
Study ID
NCT04989491
Phase
PHASE4
Status
Recruiting
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Conditions

  • Epstein-Barr Virus Infections

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Rituximab — DRUG
    One single dose of rituximab intravenously (IV)
  • control group — OTHER
    No treatment

Study Details

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.

Key Dates

Start date
Dec 1, 2021
Status verified
Aug 2024
Primary completion
Dec 1, 2029
Completion
Dec 1, 2029

Study Design

Enrollment
120 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION

Arms

  • Experimental: Experimental group
    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.
  • Active Comparator: control group
    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

Primary Outcome Measure

Primary EBV infection [ Time Frame: 1 year post-transplantation ]

Central Contacts

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