Isatuximab 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

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'.

Study Overview

• Status: Recruiting
• Conditions: Monoclonal Gammopathy
• Intervention / Treatment: Drug: Isatuximab

Detailed Description

Monoclonal gammopathy is a common disorder but only a small fraction of patients with monoclonal gammopathy of undetermined significance (MGUS) develop renal disease and the reason for abnormal deposition of immunoglobulin in renal parenchyma remains unclear in these disorders. The proposed research will be conducted as a part of clinical trial which intends to prospectively evaluate the effect of anti-plasma cell therapy on renal outcomes in patients with monoclonal gammopathy of renal significance (MGRS). The study specifically intends to sequence the immunoglobulin heavy and light chain genes to determine any abnormalities that could lead to production of a misfolded immunoglobulin thus leading to deposition in renal parenchyma.

• Study Type: Interventional
• Enrollment (Estimated): 27
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Research Nurse Navigator; Phone Number: 212-342-5162; Email: cancerclinicaltrials@cumc.columbia.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital, Renal Associates Clinic
      • Contact: Meghan Sise, MD; Email: msise@partners.org
      • Principal Investigator: Meghan Sise, MD
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Irving Medical Center
      • Principal Investigator: Divaya Bhutani, MD
      • Contact: Research Nurse Navigator; Phone Number: 212-342-5162; Email: cancerclinicaltrials@cumc.columbia.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Isatuximab for MGRS; Subjects will receive Isatuximab for 6 months and will be followed for an additional one year post therapy for outcome follow-up.	Drug: Isatuximab; Isatuximab in IV form (10mg/kg q weekly x 4 doses followed by 10mg/kg q 2 weeks) for a total of 6 month duration. Doses should be initiated at 175 mg/hour up to a maximum of 400 mg/hour. Isatuximab (SAR) is monoclonal antibody (mAb).; Other Names: Sarclisa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Renal Response Rate	Renal response defined as a decrease in 24-hour proteinuria by >50% at any point post therapy.	Up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Adverse Events	The number of adverse events recorded for participants using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.	Up to 12 months
Percentage of Participants with Immunoglobulin Gene Mutations	The percentage of participants with immunoglobulin gene mutations as determined by next generation sequencing.	Baseline, up to 4 weeks prior to treatment

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: Genzyme, a Sanofi Company
• Investigators: Principal Investigator: Divaya Bhutani, MD, Assistant Professor of Medicine at the Columbia University

Study record dates

Study Major Dates

• Study Start (Actual): June 8, 2021
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: October 29, 2020
• First Submitted That Met QC Criteria: October 29, 2020
• First Posted (Actual): November 4, 2020

Study Record Updates

• Last Update Posted (Estimated): March 6, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Immunoproliferative Disorders; Hematologic Diseases; Blood Protein Disorders; Hypergammaglobulinemia; Paraproteinemias; Monoclonal Gammopathy of Undetermined Significance
• Other Study ID Numbers: AAAT0761

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No