Desensitization in Kidney Allograft Recipients Before Transplantation Using Daratumumab

APHP190500

Patients highly allosensitized against HLA antigen awaiting for a kidney transplant have less compatible transplants to them, increasing their waitlist time and mortality. Current desensitization strategies need to be improved with a high remaining acute rejection rate in this population and a substantial survival benefit which is not uniformly reported in the literature. The investigators propose to use daratumumab, a human IgG1 (Immunoglobulin Gamma-1) monoclonal antibody directed against the CD38 molecule (cluster of differentiation 38) witch induce response in refractory multiple myeloma by depleting plasma cells, as a new agent of desensitization. The study will address the hypothesis that daratumumab can lead to a significant decrease in calculated panel reactive antibodies by elimination of anti-HLA antibodies-producing plasma cells and facilitate the access to transplantation with a safety profile in highly sensitized patients registered in our kidney transplantation center.

2020-02-18

2023-06-01

2023-06-01

Completed

Early phase I

21

Inclusion Criteria: * Adults ≥ 18 years awaiting a kidney allograft transplantation * Registration on the French National kidney allograft waiting-list for at least three years * cPRA ≥ 95% for at least three years * COVID-19 vaccination using Pfizer BioNtech vaccine for: Patients who have never been infected with COVID-19, inclusion at least one month after the third dose OR Patients previously infected with COVID-19 proved with PCR or serology, inclusion at least one month after the second injection of Pfizer BioNtech vaccine. * Effective contraception up to three months after the end of treatment * Informed consent obtained in accordance with local regulations; * Affiliation to a social security regime. Exclusion Criteria: * Refusal of COVID-19 vaccination using Pfizer BioNtech vaccine * Hypersensitivity to daratumumab or to any of the excipients), * Known allergy to methylprednisolone and its excipients or to diphenhydramine and its excipients or to acetaminophen and its excipients or to valacyclovir and its excipients. * Severe hepatocellular insufficiency * Psychotic state not yet controlled by treatment * Patient refusal * Pregnant or breastfeeding woman or ineffective contraception * Active neoplasia * Active infection * Active HBV infection, including HBsAg positive at screening * Participation in another interventional study involving human participants or being in the exclusion period at the end of a previous study involving human participants * Persons deprived of their liberty by judicial or administrative decision, * Persons under legal protection/safeguard of justice, * Patients under duress psychiatric care, * Persons admitted to a health or social institution * Patient on AME (state medical aid) * Contraindication to kidney transplantation

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2024-03-19