Novel Treatments in Improving Renal Outcomes in Light Chain Cast Nephropathy

NCT06483139 | Recruiting FDA Drug

• 1 other identifier: 2021P002205
• Study Type: observational
• Target: 450
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Myeloma; Light Chain Nephropathy; Acute Kidney Injury

Outcome Measures

Primary Outcomes (1)

• The primary composite outcome is the rate of survival with renal recovery within 90 days from the diagnosis of light chain cast nephropathy.

  To meet the primary outcome, patients must be alive, not RRT-dependent (e.g., were never on dialysis/no longer on dialysis), and have a decline of at least one stage of AKI severity compared to their highest AKI stage achieved at the time of light chain cast nephropathy-associated AKI. AKI staging will be based on the Kidney Disease Improving Global Outcomes (KDIGO) criteria, where stage 1 is a 1.5-1.9-fold rise in SCr from baseline; stage 2 is a 2-2.9-fold rise from baseline; and stage 3 is a 3-fold rise in SCr from baseline or initiation of RRT. Baseline SCr is defined as the lowest SCr in the 365 days preceding the diagnosis of light chain cast nephropathy.

  90 days

Secondary Outcomes (8)

• The proportion of patients with Receipt of RRT within 30 days, 60 days, and 90 days following diagnosis of light chain cast nephropathy

  30, 60, 90 days

• The proportion of patients with Progressive AKI

  30, 60, 90 days

• Survival to hospital discharge

  30 days

• Renal function (SCr) at hospital discharge

  30 days

• Time to first renal recovery

  180 days

Study Arms (4)

Patients treated with plasma exchange

Treated with plasma exchange ithin 30 days of diagnosis of light chain cast nephropathy

Procedure: Plasma exchange

Patients not treated with plasma exchange

Patients not treated with plasma exchange within 30 days of diagnosis of light chain cast nephropathy

Patients treated with daratumumab

Patients treated with daratumumab within 30 days of diagnosis of light chain cast nephropathy

Drug: Daratumumab

Patients not treated with daratumumab

Patients treated with daratumumab within 30 days of diagnosis of light chain cast nephropathy

Interventions

Plasma exchange PROCEDURE

Patients treated with plasma exchange within 30 days of diagnosis of light chain cast nephropathy Patients not treated with daratumumab within 30 days of diagnosis of light chain cast nephropathy

Patients treated with plasma exchange

Daratumumab DRUG

Patients treated with daratumumab within 30 days of diagnosis of light chain cast nephropathy

Patients treated with daratumumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with multiple myeloma and clinically-suspected or biopsy-proven light chain cast nephropathy

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Janssen, LP: collaborator
• Baystate Health: collaborator
• Boston Medical Center: collaborator
• Dana-Farber Cancer Institute: collaborator
• Massachusetts General Hospital: collaborator
• Mayo Clinic: collaborator
• M.D. Anderson Cancer Center: collaborator
• Medical University of South Carolina: collaborator
• H. Lee Moffitt Cancer Center and Research Institute: collaborator
• Icahn School of Medicine at Mount Sinai: collaborator
• Northwell Health: collaborator
• Ochsner Health System: collaborator
• Ohio State University: collaborator
• Stanford University: collaborator
• Texas Medical Center: collaborator
• Thomas Jefferson University: collaborator
• University of Alabama at Birmingham: collaborator
• University of California, Los Angeles: collaborator
• University of Chicago: collaborator
• University of Colorado Health: collaborator
• University of Minnesota: collaborator
• University of New Mexico: collaborator
• University of Pennsylvania: collaborator
• University of Pittsburgh: collaborator
• University of Virginia: collaborator
• University of Washington: collaborator

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02130, United States

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma; Acute Kidney Injury

Interventions

Plasma Exchange; daratumumab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Blood Transfusion; Biological Therapy; Therapeutics; Plasmapheresis; Blood Component Removal; Sorption Detoxification; Extracorporeal Circulation; Surgical Procedures, Operative

Study Officials

• Shruti Gupta, MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shruti Gupta, MD

CONTACT

5712366626; sgupta21@bwh.harvard.edu

Christina Shincovich, MD

CONTACT

cshincovich@mgh.harvard.edu

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Physician, Director of Onconephrology

Study Record Dates

• First Submitted: June 26, 2024
• First Posted: July 3, 2024
• Study Start: June 1, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: November 19, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)