Biomarkers of AKI in Patients Receiving Daratumumab

Trial Title: Biomarkers of AKI in Patients Receiving Daratumumab

NCT ID: NCT06549634

Condition: Acute Kidney Injury
Multiple Myeloma
Light Chain Nephropathy

Conditions: Official terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Acute Kidney Injury
Daratumumab

Study type: Observational

Overall status: Not yet recruiting

Study design:

Time perspective: Prospective

Intervention:

Intervention type: Drug
Intervention name: Daratumumab
Description: Daratumumab is not being administered as part of the study. Patients will receive daratumumab as part of their clinical care, and blood and urine will be collected in order to measure biomarkers pre- and post-daratumumab administration
Arm group label: Patients with multiple myeloma

Summary: 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.

Detailed description: 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.

Criteria for eligibility:

Study pop:
Patients with multiple myeloma

Sampling method: Non-Probability Sample
Criteria:
Inclusion Criteria: - 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 1. New diagnosis of systemic multiple myeloma defined as no documented history of prior multiple myeloma. 2. Further, no prior systemic treatment with anti-myeloma agent is permitted with the exception of corticosteroids for no more than 4 weeks. 3. 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 Exclusion Criteria: - 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)

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Start date: September 2024

Completion date: October 2026

Lead sponsor:
Agency: Brigham and Women's Hospital
Agency class: Other

Collaborator:
Agency: Janssen Pharmaceuticals
Agency class: Industry

Source: Brigham and Women's Hospital

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06549634