Isatuximab, Bendamustine, and Prednisone in Refractory Multiple Myeloma

March 17, 2024 updated by: Washington University School of Medicine

A Phase I/II Trial of Isatuximab, Bendamustine, and Prednisone in Refractory Multiple Myeloma

Isatuximab targets and kills CD38-positive myeloma cells in manner similar to rituximab's mechanism of action on CD20-positive lymphoma cells. Based on the synergy between rituximab and bendamustine, as well as the established clinical efficacy of bendamustine and isatuximab as single agents for multiple myeloma, the logical next step is to combine isatuximab with bendamustine and prednisone. Due to lack of effective therapies in refractory multiple myeloma, herein the investigators propose studying this novel combination in this population, in order to address a significant unmet need. The aim of the investigators is to first determine the maximal tolerated dose of the combination in participants with relapsed/refractory myeloma and then to establish the efficacy of this novel combination.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
15

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Ravi Vij, M.D.
  • Phone Number: 314-454-8304
  • Email: rvij@wustl.edu

Study Locations

  • United States
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Diagnosis of multiple myeloma with a measurable disease parameter at time of screening. A measurable disease parameter is defined as one or more of the following:

    • Serum monoclonal protein ≥ 0.5 g/dL
    • 24 hour urine monoclonal protein ≥ 200 mg/24 hour
    • Serum free light chain ratio > 5x normal ratio with an absolute difference of 10mg/dL between the involved and uninvolved free light chain
    • Soft tissue plasmacytoma ≥ 2 cm measurable by either physical examination and/or applicable radiographs (e.g. MRI, CT, etc.)
    • Bone marrow plasma cells ≥ 30%

  • Triple-class-refractory disease defined as both of the following:

    • Previously received treatment with a proteasome inhibitor, an immunomodulatory drug, and daratumumab, in combination or as single-agents.
    • Refractory (defined per IMWG Consensus Criteria as disease that is nonresponsive while on therapy, or progresses within 60 days of last dose) to most recent therapy.
  • At least 6 weeks from the last treatment with daratumumab to the first study treatment
  • At least 18 years of age.
  • Performance status of ECOG ≤ 2 Note: Participants with lower performance status based solely on bone pain secondary to multiple myeloma will be eligible.

  • Normal bone marrow and organ function as defined as ALL of the following:

    • Absolute neutrophil count ≥ 1500/mm3
    • Platelets ≥ 75,000/mm^3 (transfusions not permitted within 7 days of screening)
    • ALT (SGPT) and AST (SGOT) < 3.5 x the upper limit of the institutional normal value (ULN).
    • Total bilirubin ≤ 2.0 x mg/dL.
    • Creatinine clearance > 30 ml/min using Cockcroft-Gault formula
  • Females of childbearing potential (FCBP) must agree to refrain from becoming pregnant while on study drug and for 3 months after discontinuation from study drug, and must agree to use adequate contraception including hormonal contraception, (e.g. birth control pills, etc.), barrier method contraception (e.g. condoms), or abstinence during that time frame. Men engaging in sexual intercourse with a FCBP must agree to use adequate contraception including hormonal contraception, (e.g. birth control pills, etc), barrier method contraception (e.g. condoms), or abstinence while on study drug and for 3 months after discontinuation from study drug
  • Ability to understand and willing to sign a written informed consent document.

Exclusion Criteria:

  • Prior exposure to isatuximab or bendamustine
  • History of plasma cell leukemia or MM CNS involvement.
  • Receiving renal replacement therapy, hemodialysis, or peritoneal dialysis.
  • Diagnosed with another concurrent malignancy requiring treatment.
  • Active hepatitis A, B, or C.
  • Known intolerance to infused protein products, sucrose, histidine, polysorbate 80 or known hypersensitivity to any of the components of study therapy.
  • Receiving any other investigational agents within 14 days prior to enrollment.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
  • Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.
  • Patients with HIV are eligible unless their CD4+ T-cell counts are < 350 cells/mcL or they have a history of AIDS-defining opportunistic infection within the 12 months prior to registration. Concurrent treatment with effective ART according to DHHS treatment guidelines is recommended.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Phase I Dose Level 1: Isatuximab + Bendamustine + Prednisone
-Isatuximab (10 mg/kg) on Days 1, 8, 15, and 22 during Cycle 1 and on Days 1 and 15 of subsequent cycles. Bendamustine (50 mg/m^2) will be administered on Days 1 and 2 and prednisone (60 mg) will be administered on Days 1 through 4 of each cycle.
Biological: Isatuximab
Isatuximab will be administered on a 28-day cycle
Drug: Bendamustine
Bendamustine will be administered on a 28-day cycle as follows
Other Names:
  • Treanda
  • Bendeka
Drug: Prednisone
Prednisone will be administered on a 28-day cycle as follows
Other Names:
  • Deltasone
  • Prednisone Intensol
  • Rayos
Experimental: Phase I Dose Level 2: Isatuximab + Bendamustine + Prednisone
-Isatuximab (10 mg/kg) on Days 1, 8, 15, and 22 during Cycle 1 and on Days 1 and 15 of subsequent cycles. Bendamustine (75 mg/m^2) will be administered on Days 1 and 2 and prednisone (60 mg) will be administered on Days 1 through 4 of each cycle.
Biological: Isatuximab
Isatuximab will be administered on a 28-day cycle
Drug: Bendamustine
Bendamustine will be administered on a 28-day cycle as follows
Other Names:
  • Treanda
  • Bendeka
Drug: Prednisone
Prednisone will be administered on a 28-day cycle as follows
Other Names:
  • Deltasone
  • Prednisone Intensol
  • Rayos
Experimental: Phase I Dose Level 3: Isatuximab + Bendamustine + Prednisone
-Isatuximab (10 mg/kg) on Days 1, 8, 15, and 22 during Cycle 1 and on Days 1 and 15 of subsequent cycles. Bendamustine (100 mg/m^2) will be administered on Days 1 and 2 and prednisone (60 mg) will be administered on Days 1 through 4 of each cycle.
Biological: Isatuximab
Isatuximab will be administered on a 28-day cycle
Drug: Bendamustine
Bendamustine will be administered on a 28-day cycle as follows
Other Names:
  • Treanda
  • Bendeka
Drug: Prednisone
Prednisone will be administered on a 28-day cycle as follows
Other Names:
  • Deltasone
  • Prednisone Intensol
  • Rayos
Experimental: Phase II: Isatuximab + Bendamustine + Prednisone
-Isatuximab (10 mg/kg) on Days 1, 8, 15, and 22 during Cycle 1 and on Days 1 and 15 of subsequent cycles. Bendamustine (dose determined in Phase I portion of study) will be administered on Days 1 and 2 and prednisone (60 mg) will be administered on Days 1 through 4 of each cycle.
Biological: Isatuximab
Isatuximab will be administered on a 28-day cycle
Drug: Bendamustine
Bendamustine will be administered on a 28-day cycle as follows
Other Names:
  • Treanda
  • Bendeka
Drug: Prednisone
Prednisone will be administered on a 28-day cycle as follows
Other Names:
  • Deltasone
  • Prednisone Intensol
  • Rayos

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of regimen (Phase I only)
Time Frame: Completion of first cycle of treatment for all participants enrolled in Phase I portion (estimated to be 9 months)
The maximum tolerated dose (MTD) is defined as the dose level immediately below the dose level at which 2 participants of a cohort (of 2 to 6 participants) experience dose limiting toxicity (DLT) during the first cycle of treatment. Dose escalation will proceed until the MTD has been reached or until the maximum dose of each drug is tested (Dose Level 3). If no more than 1 DLT is observed at dose levels 1, 2 and 3, level 3 will be declared the recommended phase II dose (RP2D) and the MTD will remain undefined.
Completion of first cycle of treatment for all participants enrolled in Phase I portion (estimated to be 9 months)
Overall response rate (ORR) (Phase II only)
Time Frame: 6 months
-ORR defined as the proportion of patients meeting the criteria for partial response, very good partial response, complete response, or stringent complete response per IMWG 2016 response criteria.
6 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of adverse events experienced by participants (Phase I and Phase II)
Time Frame: From start of treatment through 30 days after completion of treatment or initiation of new anti-myeloma therapy, whichever occurs first (estimated to be 7 months)
Participants will be evaluated for toxicity according to the Common Terminology Criteria for Adverse Events (CTCAE) of the National Cancer Institute (NCI) version 5.0.
From start of treatment through 30 days after completion of treatment or initiation of new anti-myeloma therapy, whichever occurs first (estimated to be 7 months)
Progression-free survival (PFS) (Phase II only)
Time Frame: Up to 5 years after removal from study (estimated to be 5 years and 6 months)
Progression-free survival (PFS) will be defined as time from Cycle 1 Day 1 to disease progression or relapse. Any patient who expires, withdraws, or is lost to follow-up prior to disease progression or relapse will be censored at last follow-up. Patients who are removed from study therapy prior to progression or relapse will be censored at the time of initiation of subsequent anti-myeloma treatment.
Up to 5 years after removal from study (estimated to be 5 years and 6 months)
Overall survival (OS) (Phase II only)
Time Frame: Up to 5 years after removal from study (estimated to be 5 years and 6 months)
Overall survival (OS) will be defined as time from Cycle 1 Day 1 to death due to any causes. Patients who are alive at the time of data analyses will be censored on the last known alive date. Patients who are removed from study therapy prior death will be censored at the time of initiation of subsequent anti-myeloma treatment.
Up to 5 years after removal from study (estimated to be 5 years and 6 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Washington University School of Medicine

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Sanofi

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Ravi Vij, M.D., Washington University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 3, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 13, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 7, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 6, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 6, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 10, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 19, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 17, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 201910194

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

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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