Clinical trial NCT06483139: Novel Treatments in Improving Renal Outcomes in Light Chain Cast Nephropathy
Official title: The Effect of Novel Treatments in Improving Renal Outcomes Among Patients With Light Chain Cast Nephropathy
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Multiple Myeloma
Light Chain Nephropathy
Acute Kidney Injury
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: Janssen, LP
name: Baystate Health
name: Boston Medical Center
name: Dana-Farber Cancer Institute
name: Massachusetts General Hospital
name: Mayo Clinic
name: M.D. Anderson Cancer Center
name: Medical University of South Carolina
name: H. Lee Moffitt Cancer Center and Research Institute
name: Icahn School of Medicine at Mount Sinai
name: Northwell Health
name: Ochsner Health System
name: Ohio State University
name: Stanford University
name: Texas Medical Center
name: Thomas Jefferson University
name: University of Alabama at Birmingham
name: University of California, Los Angeles
name: University of Chicago
name: University of Colorado Health
name: University of Minnesota
name: University of New Mexico
name: University of Pennsylvania
name: University of Pittsburgh
name: University of Virginia
name: University of Washington
First posted: 2024-07-03
Enrollment: 450
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with multiple myeloma and clinically-suspected or biopsy-proven light chain cast nephropathy

Brief summary: Objective 1: To test whether treatment with plasma exchange improves renal recovery in patients with light chain cast nephropathy Objective 2: To compare renal outcomes among patients treated with plasma exchange versus daratumumab-based regimens versus non-daratumumab based-regimens.

Detailed description: Objective 1:

We will collect data from patients treated with plasma exchange from major centers across the United States to investigate whether plasma exchange improves renal outcomes.

Specifically, we will collect data on at least 150 patients treated with plasma exchange along with 300 control patients not treated with plasma exchange.

Objective 2:

We will compare renal outcomes among patients with light chain cast nephropathy and AKI treated with plasma exchange (n=150) versus daratumumab based regimen (eg Dara-CyborD) (n=150) versus other novel regimens (e.g., CyborD or another non-daratumumab-based regimen) (n=150). We will examine whether patients who receive dara-based regimens are more likely to have renal recovery compared to patients who do not receive dara-based regimens and to patients who receive plasma exchange. Given the infrequency with which plasma exchange is performed on a single-center level, we will compare outcomes among patients treated with plasma exchange, utilizing data from the multicenter study to those patients who were treated with daratumumab-based regimens without plasma exchange versus non- daratumumab-based regimen.

Eligibility criteria: Inclusion Criteria for Plasma Exchange-Treated Patients:

1. Adult (≥18 years old)
2. Either a new diagnosis of multiple myeloma confirmed by bone marrow plasmayctosis \>10% or acute relapse of multiple myeloma
3. Light chain cast nephropathy, with involved light chain \>500 mg/L
4. Acute kidney injury, defined as ≥1.5-fold rise in SCr from baseline (as defined in study outcomes) or the need for renal replacement therapy (RRT).
5. Treated with at least 1 round of plasma exchange within 30 days of diagnosis of cast nephropathy
6. Treated with plasma exchange in 2010 or later

Inclusion Criteria for Control Patients:

1. Adult (≥18 years old)
2. Either a new diagnosis of multiple myeloma confirmed by bone marrow plasmayctosis \>10% or acute relapse of multiple myeloma
3. Light chain cast nephropathy, with involved light chain \>500 mg/L
4. Acute kidney injury, defined as ≥1.5-fold rise in SCr from baseline or the need for renal replacement therapy (RRT)

Exclusion Criteria for Both Plasma Exchange-Treated Patients and Control Patients:

1. Patients with end stage kidney disease
2. Patients with amyloidosis or monoclonal immunoglobulin deposition disease
3. Patients with chronic lymphocytic leukemia, plasma cell leukemia, or Waldenstrom's
4. Moribund condition (e.g., patients who died within 48 hours of initiation of plasma exchange)
5. Active urinary tract obstruction on renal imaging
6. Patients with significant albuminuria (≥2+ on urinary dipstick or \>10% fraction on UPEP)
7. Patients with other biopsy-proven causes of AKI (non-cast nephropathy lesions)
8. Patients who did not receive clone-directed therapy for myeloma
9. Patients who received plasma exchange \>30 days from the time of diagnosis of cast nephropathy

Primary outcomes:
measure: The primary composite outcome is the rate of survival with renal recovery within 90 days from the diagnosis of light chain cast nephropathy.
timeFrame: 90 days
Secondary outcomes:
measure: The proportion of patients with Receipt of RRT within 30 days, 60 days, and 90 days following diagnosis of light chain cast nephropathy
timeFrame: 30, 60, 90 days
measure: The proportion of patients with Progressive AKI
timeFrame: 30, 60, 90 days
measure: Survival to hospital discharge
timeFrame: 30 days
measure: Renal function (SCr) at hospital discharge
timeFrame: 30 days
measure: Time to first renal recovery
timeFrame: 180 days
measure: Kidney recovery
timeFrame: 30 (+/-15), 60 (+/-15), 90 (+/-30) days, and 180 days (+/-60 days)
measure: Overall survival at day 90, 180, 360, with day 0 defined as date of LCCN diagnosis. Patients who die within 48 hours of the diagnosis will be excluded.
timeFrame: 90, 180, 360 days
measure: Adverse events
timeFrame: 60 days
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Shruti Gupta, MD
role: PRINCIPAL_INVESTIGATOR
References: