Effect of Daratumumab on Kidney Diseases Related to Monoclonal Gammopathy

Daratumumab in Monoclonal Gammopathy of Renal Significance in Finland

This study is testing whether daratumumab can help improve kidney function and overall health in people with kidney diseases linked to monoclonal gammopathy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Helsinki University Central Hospital (Academic / other)
• Drugs / interventions: daratumumab, rituximab, Cyclophosphamide, prednisone
• Locations: 1 site (Helsinki)
• Trial ID: NCT06889948 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the efficacy of daratumumab in treating kidney diseases categorized under monoclonal gammopathy of renal significance (MGRS) in Finland. The study aims to assess the drug's impact on renal function, proteinuria levels, and hematological endpoints, including minimal residual disease and free light chain levels. Additionally, it evaluates changes in patients' quality of life and the activation of the complement system. The trial will also monitor the rate of hematological remission and any adverse events associated with daratumumab.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with a renal biopsy confirming MGRS and specific levels of proteinuria or eGFR.

Not a fit: Patients with myeloma or systemic AL amyloidosis are unlikely to benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve kidney function and quality of life for patients with MGRS.

How similar studies have performed: While similar approaches have been explored, this specific application of daratumumab for MGRS is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. Males or females ≥ 18 years of age
2. Subject has provided informed consent prior to initiation of the study or subject's legally acceptable representative has provided informed consent prior to the study when the subject has any kind of condition that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent.
3. Renal biopsy confirmed MGRS-disease

   * Renal biopsy must not be older than 3 months before informed consent. However, if renal biopsy is older than 3 mo and the study team is convinced that major histological changes have not occurred, a biopsy older than that can exceptionally be accepted.
   * Renal transplant patients are allowed
4. Amount of proteinuria ≥ 500 mg/24 h OR eGFR ≥ 20 ml/min prior to the study
5. Previous anticlonal treatment is allowed if deemed ineffective

Exclusion Criteria:

1. Myeloma or systemic AL amyloidosis (smoldering myeloma sized plasma cell clone is allowed when in association with a documented MGRS condition and AHL amyloidosis and AH amyloidosis are included)
2. Cancer that requires treatment,
3. MGRS related to B-cell malignant disorders,
4. Known HIV infection, active hepatitis C infection (subjects with hepatitis C that achieve a sustained virologic response after antiviral therapy are allowed), or hepatitis B infection (subjects with hepatitis B surface antigen or core antibody that achieve sustained virologic response (PCR negativity in HBVNh) with antiviral therapy are permitted with a requirement for regular monitoring for reactivation for the duration of treatment on the study),
5. Pregnancy or breastfeeding,
6. Cyclophosphamide within 6 months of enrollment, or oral high-dose prednisone or equivalent within 6 weeks of enrollment;

   * prednisone or its equivalent at a dosage of ≤10 mg daily for a condition unrelated to MGRS (e.g. asthma or gout) allowed.
   * mycophenolate mofetil (MMF), calcineurin inhibitors (CNI) or azathioprine treated patients are eligible if proteinuria is not improving or if kidney function is declining despite treatment with these medications. Once therapy with daratumumab started, these medications need to be discontinued unless they are used as immunosuppressive medication due to renal transplantation.
7. In patients who previously received rituximab, reconstitution of B cells (CD19 normalized, Ly-B-CD19 lab.code 8329) required.
8. Inability to use daratumumab and to comply with the study protocol as assessed by treating nephrologist and/or hematologist (e.g. severe psychiatric illness, severe lung disease, known allergy to daratumumab)

Where this trial is running

Helsinki

• Helsinki University Hospital — Helsinki, Finland (Recruiting)

Study contacts

• Study coordinator: Minna Seppälä, MD

Conditions Kidney Failure; Paraproteinemias; Glomerulonephritis; Monoclonal gammopathy of renal significance; daratumumab