DARDAR: Desensitization in Kidney Allograft Using Daratumumab
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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 |
Drug: 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
Drug: Daratumumab full dose
- 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
|
Outcome Measures
Primary Outcome Measures
- 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
- Patient survival within one year after inclusion [Baseline (Day 0) and at six months after daratumumab treatment]
- 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
- Percentage of patients engrafted [At six months and 12 months after inclusion]
- Variation of immunoglobulin's blood titers [At baseline (Day 0), three months, six months and 12 months after daratumumab treatment]
- 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
- 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]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Adults ≥ 18 years awaiting a kidney allograft transplantation
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Registration on the French National kidney allograft waiting-list for at least three years
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cPRA≥95% for at least three years
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Effective contraception up to three months after the end of treatment
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Informed consent obtained in accordance with local regulations
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Affiliation to a social security regime
Exclusion Criteria:
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Hypersensitivity to Daratumumab or to any of the excipients),
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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.
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Severe hepatocellular insufficiency
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Psychotic state not yet controlled by treatment
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Patient refusal
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Pregnant or breastfeeding woman or ineffective contraception
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Active neoplasia
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Active infection
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Active HBV infection, including HBsAg positive at screening
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Participation in another interventional study involving human participants or being in the exclusion period at the end of a previous study involving human participants
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Persons deprived of their liberty by judicial or administrative decision,
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Persons under legal protection/security safeguard of justice,
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Patients under duress psychiatric care,
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Persons admitted to a health or social institution
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Patient on AME (state medical aid)
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Contraindication to kidney transplantation
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Henri Mondor | Créteil | France | 94000 |
Sponsors and Collaborators
- Assistance Publique - Hôpitaux de Paris
- Janssen, LP
Investigators
- Study Chair: Marie Matignon, MD, Assistance Publique - Hôpitaux de Paris
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- APHP190500