Desensitization in Kidney Allograft Recipients Before Transplantation Using Daratumumab
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Serious adverse events (SAEs) and adverse event (AEs) related and unrelated to the treatment during the dose-escalation step
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
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
干预措施: Daratumumab dose escalation (Drug)
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
干预措施: Daratumumab full dose (Drug)
结局指标
主要结局
Serious adverse events (SAEs) and adverse event (AEs) related and unrelated to the treatment during the dose-escalation step
时间窗: up to 21 months
Intra-patient variation of cPRA after daratumumab treatment
时间窗: Baseline (Day 0) and at six months after daratumumab treatment
次要结局
- 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.)
- 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)