Using Isatuximab to Improve Kidney Function in Patients with Monoclonal Gammopathy of Renal Significance

A Single Arm, Multicenter, Phase II, Open-Label Trial to Evaluate Efficacy of Isatuximab in Patients With Monoclonal Gammopathy of Renal Significance

This study is testing if Isatuximab can help improve kidney function in people with Monoclonal Gammopathy of Renal Significance.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 27 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Columbia University (other)
• Drugs / interventions: Rituximab, Isatuximab, chemotherapy
• Locations: 2 sites (Boston, Massachusetts and 1 other locations)
• Trial ID: NCT04614558 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the effectiveness of Isatuximab, an FDA-approved treatment for multiple myeloma, in improving kidney function in patients diagnosed with Monoclonal Gammopathy of Renal Significance (MGRS). The study will prospectively assess renal outcomes and investigate the genetic abnormalities associated with immunoglobulin production that may lead to kidney damage. Participants will undergo renal biopsies and proteinuria measurements to determine eligibility and monitor treatment effects. The research is considered investigational as Isatuximab is not yet approved for treating MGRS.

Who should consider this trial

Good fit: Ideal candidates include individuals with a renal biopsy-proven diagnosis of MGRS disorders and measurable proteinuria.

Not a fit: Patients who have previously received CD38 antibody therapy or do not have a confirmed diagnosis of MGRS may not benefit from this study.

Why it matters

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

How similar studies have performed: While Isatuximab has shown success in treating multiple myeloma, its application in MGRS is novel and untested.

Eligibility criteria

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.

Where this trial is running

Boston, Massachusetts and 1 other locations

• Massachusetts General Hospital, Renal Associates Clinic — Boston, Massachusetts, United States (RECRUITING)
• Columbia University Irving Medical Center — New York, New York, United States (RECRUITING)

Study contacts

• Principal investigator: Divaya Bhutani, MD — Assistant Professor of Medicine at the Columbia University
• Study coordinator: Research Nurse Navigator

Conditions: Monoclonal Gammopathy