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

NCT02812706 | Completed Phase 1 Results

• 2 other identifiers: TED14095U1111-1175-0679
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 13

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.

Conditions

Multiple Myeloma

Keywords

Anti-CD38 monoclonal antibody

Outcome Measures

Primary Outcomes (2)

• Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs)

  DLTs: AEs occurring during 1st treatment cycle, assessed per national cancer institute (NCI) common terminology criteria for adverse events (CTCAE) version 4.03. DLTs included: Hematologic DLTs: Grade(G) 4 neutropenia(N) lasting greater than or equal to (\>=) 5 days; G3 to G4 N with fever or microbiologically or radiographically documented infection; G4 thrombocytopenia lasting for \>=5 days; thrombocytopenia, treatment delay greater than (\>)14 days due to hematologic toxicity. Non-hematologic DLTs: G\>=3 non-hematological AE, excluding G3 fatigue, G 3 to 4 electrolyte abnormalities, G3 nausea/vomiting/diarrhea if responsive to optimal medical management within 48 hours or allergic reaction/ hypersensitivity attributed to isatuximab; AE that required treatment delay for \>14 days. Any other toxicity deemed by Investigator or sponsor to be dose-limiting, regardless of the grade, was also considered DLT.

  Cycle 1 (28 days)

• Phase 2: Percentage of Participants With Overall Response (OR)

  Percentage of participants with stringent complete response (sCR), complete response (CR), very good partial response (VGPR), and partial response (PR) assessed by International Myeloma Working Group (IMWG) uniform response criteria. sCR: CR as defined plus normal FLC ratio \& absence of clonal cells in bone marrow. CR: negative immunofixation on serum \& urine; disappearance of any soft tissue plasmacytomas; \<5% plasma cells in bone marrow; normal FLC ratio of 0.26-1.65. VGPR: serum \& urine M-protein detectable by immunofixation; \>=90% reduction in serum M-protein plus urine M-protein level \<100 mg/24 h; \>90% decrease in difference between involved \& uninvolved FLC levels required. PR: \>=50% reduction of serum M-protein \& reduction in 24h urinary M protein by \>=90%/\<200 mg/24 h; if serum \& urine M-protein unmeasurable:\>=50% decrease in difference between involved \& uninvolved FLC; if serum \& urine M-protein not measurable:\>=50% reduction in plasma cells required, in place of M-protein.

  From the date of the first response until the primary analysis data cut-off date of 31 July 2018 (median duration of follow-up was 24.14 weeks)

Secondary Outcomes (20)

• Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

  From first dose of study drug up to 30 days after the last dose of study drug administration (maximum duration of exposure: up to 112 weeks for Cohort 1 and 137 weeks for Cohort 2)

• Phase 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

  From first dose of study drug up to 30 days after the last dose of study drug administration (maximum duration of exposure: up to 248 weeks)

• Phase 1: Percentage of Participants With Overall Response (OR)

  From the date of the first response until disease progression, or death due to any cause, whichever comes first (maximum duration of exposure: up to 112 weeks for Cohort 1 and 137 weeks for Cohort 2)

• Phase 1: Duration of Response (DOR)

  From the date of the first response until disease progression, or death due to any cause, whichever comes first (maximum duration of exposure: up to 112 weeks for Cohort 1 and 137 weeks for Cohort 2)

• Phase 2: Percentage of Participants With Clinical Benefit (CB)

  From date of first study treatment administration until first documented response, or death due to any cause, whichever comes first (maximum duration of exposure: up to 248 weeks)

Study Arms (3)

Phase 1, Cohort 1: Isatuximab 10 mg/kg

EXPERIMENTAL

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).

Drug: Isatuximab SAR650984

Phase 1, Cohort 2: Isatuximab 20 mg/kg

EXPERIMENTAL

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).

Drug: Isatuximab SAR650984

Phase 2: Isatuximab 20 mg/kg

EXPERIMENTAL

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).

Drug: Isatuximab SAR650984

Interventions

Isatuximab SAR650984 DRUG

Pharmaceutical form: solution Route of administration: intravenous

Also known as: Sarclisa

Phase 1, Cohort 1: Isatuximab 10 mg/kg; Phase 1, Cohort 2: Isatuximab 20 mg/kg; Phase 2: Isatuximab 20 mg/kg

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (13)

Investigational Site Number :392001

Nagoya, Aichi-ken, 467-8602, Japan

Location

Investigational Site Number :392005

Shibukawa-shi, Gunma, 377-0280, Japan

Location

Investigational Site Number :392010

Hiroshima, Hiroshima, 730-8619, Japan

Location

Investigational Site Number :392015

Kanazawa, Ishikawa-ken, 920-8641, Japan

Location

Investigational Site Number :392016

Kyoto, Kyoto, 603-8151, Japan

Location

Investigational Site Number :392008

Suwa-shi, Nagano, 392-8510, Japan

Location

Investigational Site Number :392003

Okayama, Okayama-ken, 701-1192, Japan

Location

Investigational Site Number :392009

Osaka, Osaka, 543-8555, Japan

Location

Investigational Site Number :392013

Suita-shi, Osaka, 565-0871, Japan

Location

Investigational Site Number :392017

Sunto-gun, Shizuoka, 411-8777, Japan

Location

Investigational Site Number :392012

Chuo-ku, Tokyo, 104-0045, Japan

Location

Investigational Site Number :392002

Shibuya-ku, Tokyo, 150-8935, Japan

Location

Investigational Site Number :392011

Yamagata, 990-9585, Japan

Location

Related Publications (2)

• 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.

  PMID: 36433829 RESULT

• 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.

  PMID: 32975869 RESULT

MeSH Terms

Conditions

Multiple Myeloma

Interventions

isatuximab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2016
• First Posted: June 24, 2016
• Study Start: September 5, 2016
• Primary Completion: July 31, 2018
• Study Completion: September 28, 2022
• Last Updated: April 1, 2024
• Results First Posted: April 1, 2024

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will share

Locations

JP (13)