Rapid-infusion Isatuximab in Relapsed/Refractory Multiple Myeloma

Safety of Rapid-Infusion Isatuximab in Patients With Relapsed/Refractory Multiple Myeloma

This phase II trial studies the effects of isatuximab given as a rapid-infusion in treating multiple myeloma that has come back (recurrent) or has not responded to treatment (refractory). Isatuximab, also known as Sarclisa, is an antibody (proteins that can protect the body from foreign organisms, such as bacteria and viruses) directed against cluster of differentiation 38 (CD38), a receptor antigen (a receptor or protein on the outside of blood cells that can be used as a target). Isatuximab may stop the growth of some blood cancers. Normally, the fastest that intravenous isatuximab can be given - for patients who have not had any reactions to their first two doses - is over 1 hour and 15 minutes. This study is designed to test whether intravenous isatuximab can be given over 30 minutes ("rapid infusion") among patients who have not developed any reactions to at least 2 prior doses of intravenous isatuximab at normal speeds. If shown to be safe, "rapid infusion" isatuximab may ultimately improve the patient experience while reducing the overall cost of the infusion.

Study Overview

• Status: Withdrawn
• Conditions: Refractory Multiple Myeloma; Relapsed Multiple Myeloma
• Intervention / Treatment: Biological: Rapid Infusion Isatuximab

Detailed Description

PRIMARY OBJECTIVE:

I. To evaluate the incidence of grade 2 or higher (Gr2+) infusion-related reactions (IRRs) with rapid-infusion (RI) isatuximab across 6 doses.

SECONDARY OBJECTIVE:

I. To estimate time savings with RI isatuximab (versus estimated standard of care [SOC] isatuximab duration lengths) across 6 doses of isatuximab.

OUTLINE:

Patients must have received standard of care isatuximab IV over for at least 2 doses without any Gr2+ IRRs reported. Patients will then receive a rapid infusion of isatuximab IV over 30 minutes. If a >=Grade 2 iRR occurs, then participants will revert to a SOC infusion time and be taken off the study. If a Grade 1 or no IRR occurs, then participants will receive another rapid infusion of 30 minutes and assessed again for IRRs. Rapid infusions and IRR assessment after each RI will continue for up to at least 6 doses or until the patient experiences an Grade 2 or higher IRR.

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Histologically confirmed diagnosis of multiple myeloma (International Classification of Disease (ICD-10) code: C90.0)
• Previous exposure to at least one proteasome inhibitors (PI) and lenalidomide (or candidacy for isatuximab as per updated Food and Drug Administration (FDA) package insert information in the future)

• Planned or current isatuximab-containing therapy. Patients receiving isatuximab as part of a clinical trial are eligible for this study if allowed by the trial sponsor.

  • For ease of registration, patients will be allowed to enroll at any point after the decision is made to initiate isatuximab (with the understanding that their initial doses will be standard of care (SOC), including the first 2 doses for all patients). However, rapid infusion (RI) isatuximab will only be administered to participants who have not had infusion-related reactions (iRRs) during >= 2 consecutive prior doses of SOC isatuximab
• Ability to understand a written informed consent form (ICF) document, and the willingness to sign the ICF document

Exclusion Criteria:

• Age < 18
• Body weight > 70 kilograms (kg) at the time of any RI isatuximab dose
• Current pregnancy or (if of reproductive age) unwillingness to follow contraception requirements as per the FDA package insert
• New York Heart Association Stage IV heart disease, i.e. unable to carry on any physical activity without discomfort or symptoms of heart failure (as per study investigator)
• Any medical condition, including mental illness or substance abuse, deemed by the principal investigator to interfere with the ability to provide consent or cooperate with study procedures

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: Treatment (isatuximab); Participants receive their first rapid infusion of isatuximab IV over 30 minutes. If a >=Grade 2 iRR occurs, then participants will revert to a SOC infusion time and be removed from the study. If a Grade 1 or no IRR occurs, then participants will receive another rapid infusion of 30 minutes. Participants will continue to receive RI and IRR assessment after each dose up to at least 6 doses or until a grade 2 or higher IRR occurs.

Biological: Rapid Infusion Isatuximab; Given IV; Other Names: Hu 38SB19; SAR 650984; SAR650984; Sarclisa; Isatuximab-irfc; ISATUXIMAB

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with reported grade 2 or higher infusion-related reactions (IRR)	The per-patient incidence of Grade 2 or higher IRRs with rapid infusion (RI) isatuximab will be calculated as the number of patients who developed >= 1 Grade 2+ IRR with RI isatuximab divided by the total number of patients who receive >= 1 dose of RI isatuximab.	Up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean per-participant infusion duration	Descriptive statistics for total infusion durations in minutes including mean, standard deviation, and 95% confidence interval will be reported across the first 6 doses of RI isatuximab.	9-12 weeks depending on isatuximab dosing interval

Collaborators and Investigators

• Sponsor: Thomas Martin, MD

Study record dates

Study Major Dates

• Study Start (Actual): May 28, 2021
• Primary Completion (Anticipated): November 30, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: March 13, 2021
• First Submitted That Met QC Criteria: March 13, 2021
• First Posted (Actual): March 17, 2021

Study Record Updates

• Last Update Posted (Actual): July 7, 2022
• Last Update Submitted That Met QC Criteria: July 3, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Isatuximab Infusion
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: 202530; NCI-2021-01226 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

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.: No