Overview

The purpose of this study is to see whether Isatuximab can help improve kidney function of participants with MGRS. Isatuximab is approved by the Food and Drug Administration (FDA) for the treatment of adult patients with multiple myeloma, but it is not approved by the FDA to treat MGRS. This means that the use of isatuximab in this study is considered 'investigational'.

Eligibility

Inclusion Criteria:

1. Renal biopsy proven diagnosis of an MGRS disorder including the following:
   1. Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID)
   2. C3 glomerulopathy associated with monoclonal gammopathy
   3. Non-Amyloid Fibrillary Glomerulonephritis
   4. Light chain Proximal Tubulopathy
   5. Immunotactoid Glomerulopathy

             A concurrent diagnosis of Monoclonal gammopathy (with +ve Serum and/or Urine protein
             electrophoresis or Bone marrow biopsy) is required in patients with C3 glomerulopathy
             but not for other disorders. Patients with concurrent MGUS, non-high risk smoldering
             myeloma are eligible for enrollment.
          2. Measurable Proteinuria ≥1gram over 24 hours.
          3. Prior Therapy: Newly diagnosed as well as patients with previous therapy but
             persistent renal dysfunction and persistent proteinuria ≥1gram over 24 hours are
             eligible for enrollment. Patients who received a prior cluster of differentiation 38
             (CD38) antibody therapy are not eligible for study. In patients who have received
             prior therapy a wash out period of 12 weeks for chemotherapy based therapies and 24
             weeks for Rituximab based therapies is required between completion of prior therapy
             and cycle 1 Day1 of study therapy.
          4. Age ≥18 years.
          5. Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
          6. Life expectancy of greater than 6 months
          7. Participants must have normal organ and marrow function as defined below:
        Leukocytes ≥3,000/microliters (mcL)
          1. absolute neutrophil count ≥1,500/mcL
          2. platelets ≥100,000/mcL
          3. total bilirubin within normal institutional limits
          4. Aspartate aminotransferase (AST) (SGOT)/alanine transaminase (ALT)(SGPT) ≤2.5 ×
             institutional upper limit of normal
          5. Estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2.
        Exclusion Criteria:
          1. Participants who have had chemotherapy based therapy within 12 weeks or Rituximab
             based therapy within prior 24 weeks prior to starting the cycle 1 Day 1 of trial
             therapy
          2. Participants who are receiving any other investigational agents concurrently.
          3. History of severe allergic reactions or anaphylaxis attributed to compounds of similar
             chemical or biologic composition to Isatuximab.
          4. Diagnosis of Multiple Myeloma or High risk smoldering Multiple Myeloma or a B cell
             lymphoma meeting criteria for therapy.
          5. Renal Biopsy showing the coexistence of other significant diagnosis e.g. diabetic
             nephropathy.
          6. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.
          7. Pregnant and Lactating women are excluded from this study because there is an unknown
             but potential risk for adverse events in nursing infants secondary to treatment of the
             mother with Isatuximab.
          8. HIV-positive Participants are ineligible because of increased risk of lethal
             infections when treated with immunosuppressive therapy.