Daratumumab in Treatment of PGNMID and C3 GN

This study is an open-label phase 2 trial of the safety and efficacy of daratumumab, in the treatment of PGNMID and C3GN associated with monoclonal gammopathy. Subjects will be screened at outpatient Nephrology Clinic visit appointments and interested qualified subjects will be consented and offered participation in this trial. Once consent has been obtained baseline values will be established and subjects will begin treatment and follow-up for the next 12 months. Daratumumab will be administered once weekly for 8 weeks and then once every 2 weeks for 8 additional doses. Patients will be followed for a total of 12 months (6 months after the last infusion). A final visit for evaluation and collection of lab samples will be conducted at the end of the study.

Inclusion criteria

• Age ≥ 18 years of age
• Renal biopsy read at Mayo Clinic confirming the diagnosis of PGNMID or C3 GN
• In cases of C3GN serum electrophoresis with immunofixation should confirm presence of monoclonal gammopathy
• Proteinuria ≥ 1000 mg over 24 hours
• eGFR ≥ 20 mL/min/SA
• Subjects able and willing to give informed consent

Exclusion criteria

• Pregnancy
• Hepatitis B or C, HIV
• Multiple myeloma
• Anemia with Hgb < 8.5 g/dL
• Thrombocytopenia with platelet count < 100,000
• Leukopenia with WBC < 3.5
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complication
• Unable to provide consent
• Patients receiving therapy with oral prednisone or glucocorticoid equivalent in the last 6 weeks
• Patients who had received immunosuppressive therapy including cyclophosphamide, MMF, cyclosporine, tacrolimus or azathioprine in the last 3 months
• Patients who received rituximab previously with CD20 count of zero at the time of enrollment