Desensitization in Kidney Allograft Using Daratumumab

Sponsor
Assistance Publique - Hôpitaux de Paris
Study ID
NCT04204980
Phase
PHASE1/PHASE2
Status
Completed

Conditions

  • Allosensitization
  • Antibody-mediated Rejection
  • Kidney Transplant Rejection

Eligibility Criteria

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

Interventions

  • Daratumumab dose escalation — DRUG
    \- 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
  • Daratumumab full dose — DRUG
    \- 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

Study Details

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.

Key Dates

Start date
Feb 18, 2020
Status verified
Feb 2023
Primary completion
Jun 1, 2023
Completion
Jun 1, 2023

Study Design

Enrollment
21 participants (actual)
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: Dose escalation and 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

Primary Outcome Measure

Serious adverse events (SAEs) and adverse event (AEs) related and unrelated to the treatment during the dose-escalation step [ Time Frame: up to 21 months ]

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