Biomarkers of AKI in Patients with Multiple Myeloma Receiving Daratumumab: a Pilot Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Plasma and Urine Biomarkers
研究概览
简要总结
The goal of this prospective observational study is to understand changes in urinary and blood biomarkers associated with acute kidney injury (AKI) in patients newly diagnosed with multiple myeloma and being treated with Daratumumab SC. The aims of the study are:
To measure changes in plasma and urinary biomarkers of AKI before initiation of Daratumumab therapy and 30 days after initiation of therapy.
To establish whether these biomarkers serve to aid in early detection and prevention of AKI
Participants will give urine and blood samples at their normally scheduled lab appointments.
详细描述
Serum creatinine is an insensitive marker of AKI, often rising late and after significant injury has already occurred. A number of novel markers have recently been shown to have utility in the early detection of AKI. These markers have shown promise in preclinical and human studies in multiple other clinical settings (e.g., cardiac surgery, coronary angiography, critical illness), but have not been studied in the context of multiple myeloma. Specifically, elevated pre-procedural plasma levels of soluble urokinase-type plasminogen activator receptor (suPAR), the circulating form of a membrane-bound protein expressed by immunologically active cells, have been demonstrated to be predictive of AKI patients undergoing coronary angiography, cardiac surgery, and in critically ill patients (Hayek et al., NEJM, 2020), and levels rise early after injury. Similarly, urinary levels of Dickkoph-3 (DKK3), a stress-induced tubular epithelia-derived glycoprotein, have been demonstrated to predict AKI after cardiac surgery and following administration of iodinated contrast (Schunk et al., Lancet, 2019).
The aim of this study is to conduct a pilot, prospective, non-interventional study testing changes in novel plasma and urinary biomarkers of kidney injury in patients with newly-diagnosed multiple myeloma treated with daratumumab who are at risk for AKI.
The hypothesis is that patients with multiple myeloma and at risk for developing AKI, but without AKI at baseline, will have at least a 10% decline in plasma soluble urokinase-type plasminogen activator receptor and urinary levels of Dickkoph-3 following treatment with daratumumab.
The primary outcome(s) will be changes in plasma suPAR and urinary levels of DKK3 between treatment initiation of daratumumab (day 0, or up to 7 days prior) and day +30 (+/-7 days) from the time of treatment initiation.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
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
- •Patients must be ≥ 18 years of age
- •Patients can be on a clinical trial
- •Patients must have had a confirmed new diagnosis of MM following revised IMWG criteria
- •New diagnosis of systemic multiple myeloma defined as no documented history of prior multiple myeloma.
- •Further, no prior systemic treatment with anti-myeloma agent is permitted with the exception of corticosteroids for no more than 4 weeks.
- •Prior history of receiving radiation therapy for the treatment of plasmacytoma or lytic lesions, is permitted on the study.
- •Patients receiving SC daratumumab
- •Patients must be able to sign the informed consent
- •Patients must be at risk for AKI and meet at least two of the three following criteria: age ≥65; baseline eGFR <60; or use of NSAIDs (not including aspirin), bisphosphonates, intravenous contrast, diuretics, or RAS inhibitors in the 14 days preceding treatment initiation
排除标准
- •End stage renal disease (e.g, on long-term dialysis or with a kidney transplant and on long-term dialysis) at the time of starting daratumumab
- •Acute kidney injury defined as a ≥1.5-fold rise in baseline SCr, where baseline SCr is the lowest SCr in the 365 days preceding receipt of daratumumab, or with AKI on RRT
- •Previous exposure to daratumumab or other anti-CD38 therapy
- •Patients receiving intravenous daratumumab
- •Exposure to concomitant chemotherapy which could be perceived as nephrotoxic within 30 days of receipt of daratumumab (e.g., cisplatin, mTOR inhibitors)
- •Moribund patients (e.g., those expected to die in the next 30 days from the time of screening)
研究组 & 干预措施
Patients with multiple myeloma
Patients with multiple myeloma being newly initiated on daratumumab
干预措施: Daratumumab (Drug)
结局指标
主要结局
Plasma and Urine Biomarkers
时间窗: 30 days
The primary outcome(s) will be changes in plasma suPAR and urinary levels of DKK3 between treatment initiation of daratumumab (day 0, or up to 7 days prior) and day +30 (+/-7 days) from the time of treatment initiation.
次要结局
未报告次要终点
研究者
Shruti Gupta
Associate Physician, Director of Onconephrology
Brigham and Women's Hospital