search
Back to results

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 (REPLY)

Primary Purpose

Epstein-Barr Virus Infections

Status
Recruiting
Phase
Phase 4
Locations
France
Study Type
Interventional
Intervention
Rituximab
control group
Sponsored by
University Hospital, Strasbourg, France
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Epstein-Barr Virus Infections

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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:

-

Sites / Locations

  • Les Hôpitaux Universitaires de StrasbourgRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Experimental group

control group

Arm Description

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.

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

First Posted
July 15, 2021
Last Updated
August 18, 2023
Sponsor
University Hospital, Strasbourg, France
search

1. Study Identification

Unique Protocol Identification Number
NCT04989491
Brief Title
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
Acronym
REPLY
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

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 1, 2021 (Actual)
Primary Completion Date
December 1, 2029 (Anticipated)
Study Completion Date
December 1, 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Strasbourg, France

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Epstein-Barr Virus Infections

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Experimental group
Arm Type
Experimental
Arm Description
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.
Arm Title
control group
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
One single dose of rituximab intravenously (IV)
Intervention Type
Other
Intervention Name(s)
control group
Intervention Description
No treatment
Primary Outcome Measure Information:
Title
Primary EBV infection
Description
Infection assessed by a positive blood EBV viral load and/or EBV seroconversion and/or occurrence of a post-transplant lymphoproliferative disorder
Time Frame
1 year post-transplantation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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: -
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sophie Ohlmann-Caillard
Phone
0369550511
Email
sophie.caillard@chru-strasboourg.fr
Facility Information:
Facility Name
Les Hôpitaux Universitaires de Strasbourg
City
Strasbourg
ZIP/Postal Code
67000
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sophie Caillard, MD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

We'll reach out to this number within 24 hrs