Isatuximab Single Agent Study in Japanese Relapsed AND Re... | NCT02812706

NCT02812706

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
U1111-1175-0679	Other Identifier	UTN

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
Isatuximab SAR650984	Drug	Pharmaceutical form: solution Route of administration: intravenous	Phase 1, Cohort 1: Isatuximab 10 mg/kg Phase 1, Cohort 2: Isatuximab 20 mg/kg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

Measure	Description	Time Frame
Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)	An AE was defined as any untoward medical occurrence in a participant or clinical investigation patient administered with a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. TESAEs was defined as any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were defined as AEs that develop, worsened or became serious during the on-treatment period (time from first dose of study drug up to 30 days after the last dose of study drug administration).

Eligibility Module

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.

Name	Affiliation	Role
Clinical Sciences & Operations	Sanofi	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Investigational Site Number :392001		Nagoya	Aichi-ken	467-8602	Japan
Investigational Site Number :392005

PubMed Identifier	Type	Citation	Retractions
36433829	Result	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.
32975869

IPD Sharing Statement Module

Arm/Group Information

ID	Title	Description
FG000	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 (AEs), disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 112 weeks).
FG001	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 AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 137 weeks).
FG002	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 AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 248 weeks).

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Phase 1, Cohort 1: Isatuximab 10 mg/kg	Participants received Isatuximab 10 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 AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 112 weeks).

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type	Title	Description	Population Description	Reporting Status	Anticipated Posting Date	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Time Frame	Units Analyzed	Denominator Units Selected	Arm/Group Information	Denominators	Classes	Analyses
Primary	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.	Analysis was performed on DLT evaluable population that included subset of participants who completed the first Cycle which consisted of 4 isatuximab administrations of the study drug or they discontinued study drug before completion of first cycle for a DLT. .	Posted		Count of Participants		Participants		Cycle 1 (28 days)

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Phase 1, Cohort 1: Isatuximab 10 mg/kg	Participants received Isatuximab 10 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 AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 112 weeks).

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Disseminated Intravascular Coagulation	Blood and lymphatic system disorders	MedDRA 22.0	Systematic Assessment

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Bronchitis	Infections and infestations	MedDRA 22.0	Systematic Assessment

Title	Organization	Phone	Extension	Email
Trial Transparency Team	Sanofi aventis recherche & développement	800-633-1610	6#	Contact-US@sanofi.com

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jul 15, 2020	Aug 31, 2023	Prot_000.pdf
SAP	No	Yes	No	Statistical Analysis Plan	Aug 30, 2018	Aug 31, 2023	SAP_001.pdf

ID	Term
D009101	Multiple Myeloma

ID	Term
D054219	Neoplasms, Plasma Cell
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D020141	Hemostatic Disorders

ID	Term
C000599209	isatuximab

ID	Title	Description
OG000	Phase 1, Cohort 1: Isatuximab 10 mg/kg	Participants received Isatuximab 10 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 AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 112 weeks).
OG001	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 AEs, disease progression, or any other reason for discontinuation whichever occurs first (maximum duration of exposure: 137 weeks).