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Completed

NCT Number: NCT04204980

Desensitization in Kidney Allograft Using Daratumumab

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.

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Key information

Conditions

Allosensitization Antibody-mediated Rejection Kidney Transplant Rejection

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Henri Mondor

Créteil, 94000, France

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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

Primary outcomes

  1. 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

  2. Intra-patient variation of cPRA after daratumumab treatment

    Time frame: Baseline (Day 0) and at six months after daratumumab treatment

Secondary outcomes

  1. Patient survival within one year after inclusion

    Time frame: Baseline (Day 0) and at six months after daratumumab treatment

  2. Intra-patient variation of sum of mean fluorescence intensity (MFI) of anti-HLA antibodies

    Time frame: 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.

  3. Intra-patient variation of cPRA (calculated panel reactive antibodies) after daratumumab treatment

    Time frame: 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

  4. Percentage of patients engrafted

    Time frame: At six months and 12 months after inclusion

  5. Variation of immunoglobulin's blood titers

    Time frame: At baseline (Day 0), three months, six months and 12 months after daratumumab treatment

  6. Intra-patient variation of ABO antibody titers

    Time frame: At baseline (Day 0), three months, six months and 12 months after daratumumab treatment

    ABO antibody titration will be performed by flow cytometry

  7. Incidence of invasive infections

    Time frame: 6 months and on year after inclusion

  8. Incidence of opportunistic infections

    Time frame: 6 months and one year after inclusion

  9. Absolute number of Blood plasma cell

    Time frame: At baseline (Day 0), one month, three months , six months and 12 months after daratumumab treatment

  10. Percentage of Blood plasma cell

    Time frame: At baseline (Day 0), one month, three months , six months and 12 months after daratumumab treatment

Sponsors and collaborators

Lead sponsor

Assistance Publique - Hôpitaux de Paris

Other

Collaborators

  • Janssen, LP

Registry information

Official study title

Desensitization in Kidney Allograft Recipients Before Transplantation Using Daratumumab

Acronym: DARDAR

Important dates

Study start
2020
Primary completion
2023
Study completion
2023
First posted
Dec 19, 2019
Registry last updated
Mar 19, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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