Clinical trial NCT04989491: 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
Official title: Multicenter Randomized Two Arms Study Evaluating the Efficacy of Prophylactic Rituximab in Adult EBV Negative Kidney Transplant Recipients on Incidence of EBV Primary Infection and Post-transplant Lymphoproliferative Disorders
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Epstein-Barr Virus Infections
Lead sponsor: University Hospital, Strasbourg, France
Sponsor class: OTHER
First posted: 2021-08-04
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion criteria:

* 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
* Patient currently participating in another clinical trial investigating drugs. Observational studies are not considered as an exclusion criterion
* 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.

Exclusion Criteria:

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Primary outcomes:
measure: Primary EBV infection
timeFrame: 1 year post-transplantation
Secondary outcomes:
Other outcomes:
Locations:
city: Strasbourg
country: France
facility: Les Hôpitaux Universitaires de Strasbourg
Study officials:
References: