Isatuximab Single Agent Study in Japanese Relapsed AND Refractory Multiple Myeloma Patients

NCT ID: NCT02812706

Last Updated: 2024-04-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-05
• Study Completion Date: 2022-09-28

Brief Summary

Primary Objectives:

• Phase I: To evaluate safety and tolerability of isatuximab in Japanese participants with relapsed and refractory multiple myeloma.
• Phase II: To evaluate efficacy of isatuximab at recommended dose and to further evaluate the overall response rate (ORR) of isatuximab in Japanese participants with relapsed and refractory multiple myeloma.

Secondary Objectives:

• To evaluate the safety including immunogenicity of isatuximab. The severity, frequency and incidence of all adverse events were assessed.
• To evaluate the pharmacokinetic (PK) profile of isatuximab in the proposed dosing schedule.
• To assess the efficacy using International Myeloma Working Group (IMWG) uniform response criteria.
• To assess the relationship between Baseline cluster of differentiation 38 (CD38) receptor density on multiple myeloma cells and efficacy.

Detailed Description

The study duration for an individual participant included a screening period for inclusion of up to 21 days, the treatment period consisting of 28-day cycles and a follow-up period. Treatment with isatuximab might continue until disease progression, unacceptable adverse event, or other reason for discontinuation.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 1, Cohort 1: Isatuximab 10 mg/kg

Participants received Isatuximab 10 milligram per kilogram (mg/kg) intravenous (IV) infusion once every week (QW) for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then every 2 weeks (Q2W) (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable adverse events, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 112 weeks).

Group Type: EXPERIMENTAL

Isatuximab SAR650984

Intervention Type: DRUG

Pharmaceutical form: solution Route of administration: intravenous

Phase 1, Cohort 2: Isatuximab 20 mg/kg

Participants received Isatuximab 20 mg/kg IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable adverse events, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 137 weeks).

Group Type: EXPERIMENTAL

Isatuximab SAR650984

Intervention Type: DRUG

Pharmaceutical form: solution Route of administration: intravenous

Phase 2: Isatuximab 20 mg/kg

Participants received Isatuximab 20 mg/kg IV infusion, QW for 4 weeks (i.e., on Day 1, Day 8, Day 15 and Day 22 of Cycle 1), and then Q2W (i.e., on Day 1 and 15) for subsequent treatment cycles (each cycle of 28 days) until unacceptable adverse events, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 248 weeks).

Group Type: EXPERIMENTAL

Isatuximab SAR650984

Intervention Type: DRUG

Pharmaceutical form: solution Route of administration: intravenous

Interventions

Isatuximab SAR650984

Pharmaceutical form: solution Route of administration: intravenous

Intervention Type: DRUG

Other Intervention Names

Sarclisa

Eligibility Criteria

Inclusion Criteria

• Males or females, age 20 years or older.
• Participants had a known diagnosis of symptomatic multiple myeloma.
• Participants had received at least 3 prior lines of therapies OR participants whose disease was double refractory to an Immunomodulatory Drug (IMiD) and a Proteasome Inhibitor (PI).
• Participants had been responsive (i.e., minimal response [MR] or better) to at least one prior line of therapy.
• Refractory to the most recently received IMiD or PI included therapy.
• Participants with measurable disease defined as at least one of the following:
• Immunoglobulin G (IgG) Type: Serum M-protein >=1 gram per deciliter (g/dL) (>=10 g/L);
• Immunoglobulin A (IgA) and D Type: Serum M-protein, quantification should be performed;
• Urine M-protein ≥200 mg/24 hours.
• Participants with a Eastern Cooperative Oncology Group (ECOG) performance status <=2.

Exclusion Criteria

• Participants treated with any anti-CD38 agent.
• Diagnosed or treated for another malignancy within 5 years prior to enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in-situ malignancy, or low-risk prostate cancer after curative therapy.
• Prior anticancer therapy (chemotherapy, targeted agents, immunotherapy) within 21 days prior to the first drug infusion unless otherwise specified below:
• Alkylating agents (e.g., Melphalan) within 28 days prior to the first dose of study treatment.
• Steroids treatment (e.g., prednisone greater than (>)10 mg/day orally or equivalent except patients being treated for adrenal insufficiency/replacement therapy or treated for inhalation corticosteroids) within 14 days prior to the first dose of study treatment.
• Participated in another clinical trial within 30 days prior to the first dose of study treatment.
• Participants treated with systemic radiation therapy within 4 weeks prior to the first dose of study treatment OR Localized radiation therapy within 1 week prior to the first dose of study treatment.
• Major surgical procedure within 4 weeks prior to the first dose of study treatment.
• Any toxicity Grade >=2 (excluding alopecia, neutropenia or neuropathy) related to any prior anti-cancer therapy according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.
• Neuropathy Grade >=3 or painful peripheral neuropathy Grade >=2.
• History of significant cardiovascular disease unless the disease within the past 6 months was well-controlled.
• Previously received an allogenic stem cell transplant.
• Diagnosed Crow-Fukase (POEMS) syndrome OR plasma cell leukemia.
• Participants with known or suspected amyloidosis.
• Participants with Waldenstrom's macroglobulinemia OR Multiple myeloma IgM subtype.
• Participants with active infection.
• Known human immunodeficiency virus (HIV) or active hepatitis B or C viral infection.
• Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse follow-up evaluation.
• Any severe underlying medical conditions including presence of laboratory abnormalities, which could impair the ability to participate in the study or the interpretation of its results.
• Hypersensitivity or history of intolerance to boron or mannitol, sucrose, histidine (as base and hydrochloride salt) and polysorbate 80 or any of the components of study therapy that are not amenable to pre-medication with steroids and H2 blockers or would prohibit further treatment with these agents.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number :392001

Nagoya, Aichi-ken, Japan

Investigational Site Number :392005

Shibukawa-shi, Gunma, Japan

Investigational Site Number :392010

Hiroshima, Hiroshima, Japan

Investigational Site Number :392015

Kanazawa, Ishikawa-ken, Japan

Investigational Site Number :392016

Kyoto, Kyoto, Japan

Investigational Site Number :392008

Suwa-shi, Nagano, Japan

Investigational Site Number :392003

Okayama, Okayama-ken, Japan

Investigational Site Number :392009

Osaka, Osaka, Japan

Investigational Site Number :392013

Suita-shi, Osaka, Japan

Investigational Site Number :392017

Sunto-gun, Shizuoka, Japan

Investigational Site Number :392012

Chuo-ku, Tokyo, Japan

Investigational Site Number :392002

Shibuya-ku, Tokyo, Japan

Investigational Site Number :392011

Yamagata, , Japan

Countries

Japan

References

Sunami K, Fuchida SI, Suzuki K, Ri M, Matsumoto M, Shimazaki C, Asaoku H, Shibayama H, Ishizawa K, Takamatsu H, Ikeda T, Maruyama D, Imada K, Uchiyama M, Kiguchi T, Iyama S, Murakami H, Onishi R, Tada K, Iida S. Anti-CD38 antibody isatuximab monotherapy for Japanese individuals with relapsed/refractory multiple myeloma: An update of the phase 1/2 ISLANDs study. Hematol Oncol. 2023 Aug;41(3):442-452. doi: 10.1002/hon.3105. Epub 2022 Dec 15.

Reference Type: RESULT

PMID: 36433829 (View on PubMed)

Sunami K, Suzuki K, Ri M, Matsumoto M, Shimazaki C, Asaoku H, Shibayama H, Ishizawa K, Takamatsu H, Ikeda T, Maruyama D, Kaneko H, Uchiyama M, Kiguchi T, Iyama S, Murakami H, Takahashi K, Tada K, Mace S, Guillemin-Paveau H, Iida S. Isatuximab monotherapy in relapsed/refractory multiple myeloma: A Japanese, multicenter, phase 1/2, safety and efficacy study. Cancer Sci. 2020 Dec;111(12):4526-4539. doi: 10.1111/cas.14657. Epub 2020 Oct 15.

Reference Type: RESULT

PMID: 32975869 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U1111-1175-0679

Identifier Type: OTHER

Identifier Source: secondary_id

TED14095

Identifier Type: -

Identifier Source: org_study_id