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Isatuximab in Patients With Monoclonal Gammopathy of Renal Significance

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ClinicalTrials.gov Identifier: NCT04614558
Recruitment Status : Not yet recruiting
First Posted : November 4, 2020
Last Update Posted : July 27, 2021
Sponsor:
Collaborator:
Genzyme, a Sanofi Company
Information provided by (Responsible Party):
Divaya Bhutani, Columbia University

Brief Summary:
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'.

Condition or disease Intervention/treatment Phase
Monoclonal Gammopathy Drug: Isatuximab Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 27 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: The study will be a single arm, prospective, multi-center, phase II, open- label study including 27 subjects in total. The study will consist of a screening phase, treatment phase, post-treatment observation phase and follow-up phase
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Single Arm, Multicenter, Phase II, Open-Label Trial to Evaluate Efficacy of Isatuximab in Patients With Monoclonal Gammopathy of Renal Significance
Estimated Study Start Date : November 2021
Estimated Primary Completion Date : April 2023
Estimated Study Completion Date : June 2023


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 Name: Sarclisa




Primary Outcome Measures :
  1. Overall Renal Response Rate [ Time Frame: Up to 6 months ]
    Renal response defined as a decrease in 24-hour proteinuria by >50% at any point post therapy.


Secondary Outcome Measures :
  1. Number of Adverse Events [ Time Frame: Up to 12 months ]
    The number of adverse events recorded for participants using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  2. Percentage of Participants with Immunoglobulin Gene Mutations [ Time Frame: Baseline, up to 4 weeks prior to treatment ]
    The percentage of participants with immunoglobulin gene mutations as determined by next generation sequencing.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04614558


Contacts
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Contact: Research Nurse Navigator 212-342-5162 cancerclinicaltrials@cumc.columbia.edu

Locations
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United States, New York
Columbia University Irving Medical Center
New York, New York, United States, 10032
Contact: Research Nurse Navigator    212-342-5162    cancerclinicaltrials@cumc.columbia.edu   
Principal Investigator: Divaya Bhutani, MD         
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Contact: Jonathan Hogan, MD    215-662-2638    Jonathan.Hogan2@pennmedicine.upenn.edu   
Principal Investigator: Jonathan Hogan, MD         
Sponsors and Collaborators
Columbia University
Genzyme, a Sanofi Company
Investigators
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Principal Investigator: Divaya Bhutani, MD Assistant Professor of Medicine at the Columbia University
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Responsible Party: Divaya Bhutani, Assistant Professor of Medicine, Columbia University
ClinicalTrials.gov Identifier: NCT04614558    
Other Study ID Numbers: AAAT0761
First Posted: November 4, 2020    Key Record Dates
Last Update Posted: July 27, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Paraproteinemias
Monoclonal Gammopathy of Undetermined Significance
Blood Protein Disorders
Hematologic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hypergammaglobulinemia