Desensitization in Kidney Allograft Using Daratumumab
Phase 1
Completed
- Conditions
- AllosensitizationKidney Transplant RejectionAntibody-mediated Rejection
- Interventions
- Registration Number
- NCT04204980
- Lead Sponsor
- Assistance Publique - Hôpitaux de Paris
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose escalation and full dose Daratumumab full dose Step I: dose-escalation 3 patients treated weekly during four weeks with 4 mg/kg of daratumumab, then 3 patients treated weekly during four weeks with 8 mg/kg of daratumumab, then 3 patients treated weekly four weeks with 16 mg/kg of daratumumab Step II: expansion cohort to 13 patients (with 10 new patients included and the last 3 patients from the step I) with eight weekly doses of 16 mg/kg daratumumab Dose escalation and full dose Daratumumab dose escalation Step I: dose-escalation 3 patients treated weekly during four weeks with 4 mg/kg of daratumumab, then 3 patients treated weekly during four weeks with 8 mg/kg of daratumumab, then 3 patients treated weekly four weeks with 16 mg/kg of daratumumab Step II: expansion cohort to 13 patients (with 10 new patients included and the last 3 patients from the step I) with eight weekly doses of 16 mg/kg daratumumab
- Primary Outcome Measures
Name Time Method Serious adverse events (SAEs) and adverse event (AEs) related and unrelated to the treatment during the dose-escalation step up to 21 months Intra-patient variation of cPRA after daratumumab treatment Baseline (Day 0) and at six months after daratumumab treatment
- Secondary Outcome Measures
Name Time Method Intra-patient variation of sum of mean fluorescence intensity (MFI) of anti-HLA antibodies Baseline (Day 0) and at one month, three months, six months and 12 months after daratumumab treatment.Baseline (Day 0) and at one, three, six and 12 months after daratumumab treatment. Intra-patient variation of cPRA (calculated panel reactive antibodies) after daratumumab treatment Baseline (Day 0) and at one month, three months and 12 months after daratumumab treatment. PRA will be calculated on serum, analyzed with Luminex single antigen assays
Variation of immunoglobulin's blood titers At baseline (Day 0), three months, six months and 12 months after daratumumab treatment Incidence of invasive infections 6 months and on year after inclusion Incidence of opportunistic infections 6 months and one year after inclusion Absolute number of Blood plasma cell At baseline (Day 0), one month, three months , six months and 12 months after daratumumab treatment Percentage of Blood plasma cell At baseline (Day 0), one month, three months , six months and 12 months after daratumumab treatment Patient survival within one year after inclusion Baseline (Day 0) and at six months after daratumumab treatment Percentage of patients engrafted At six months and 12 months after inclusion Intra-patient variation of ABO antibody titers At baseline (Day 0), three months, six months and 12 months after daratumumab treatment ABO antibody titration will be performed by flow cytometry
Trial Locations
- Locations (1)
Henri Mondor
🇫🇷Créteil, France