Multiple Myeloma Clinical Trial

Phase 1/2 Dose Escalation and Efficacy Study of Anti-CD38 Monoclonal Antibody in Patients With Selected CD38+ Hematological Malignancies

Summary

Primary Objective:

Phase 1:

To determine the maximum tolerated dose (MTD)/maximum administered dose (MAD) of SAR650984 (treatment-a-promising-new-option-for-relapsed-multiple-myeloma/" >Isatuximab).

Phase 2 (stage 1):

To evaluate the activity of single-agent Isatuximab at different doses/schedules and to select dose and regimen to further evaluate the overall response rate (ORR) of Isatuximab as single agent or in combination with dexamethasone.

Phase 2 (stage 2):

To evaluate the activity in terms of overall response rate (ORR) of Isatuximab at the selected dose/schedule from stage1, as single agent (ISA arm) and in combination with dexamethasone (ISAdex arm).

Secondary Objectives:

Phase 1:

To characterize the global safety profile including cumulative toxicities.
To evaluate the pharmacokinetic (PK) profile of Isatuximab in the proposed dosing schedule(s).
To assess the pharmacodynamics (PD), immune response, and preliminary disease response.

Phase 2 (stage 1): to evaluate the following objectives for Isatuximab as single agent:

Safety
Efficacy as measured by duration of response, clinical benefit rate, progression free survival, overall survival.

Phase 2 (stage 2): to evaluate the following objectives in each arm (ISA and ISAdex):

Safety
Efficacy as measured by duration of response, clinical benefit rate, progression free survival, overall survival.
Participant-reported changes in health-related quality of life, symptoms of multiple myeloma and generic health status.
Pharmacokinetic profile of Isatuximab.
Immunogenicity of Isatuximab.
Investigate the relationship between CD38 receptor density and CD38 receptor occupancy (Stage 1 only) on multiple myeloma cells and parameters of clinical response.

View Full Description

Full Description

The Phase 1 study duration for an individual participant included a screening period for inclusion of up to 2 weeks, treatment with Isatuximab QW (every week) or Q2W (every 2 weeks) unless discontinued earlier due to safety or disease progression. Participants were followed for a minimum of 30 days following the last use of study drug or more than 30 days in case of unresolved toxicity, or up to initiation of another anticancer treatment.

The Phase 2 study duration for an individual participant included a screening period for inclusion of up to 3 weeks, then a treatment period and a follow up period. Treatment was continued until disease progression, unacceptable adverse reactions or other reasons for discontinuation. Participants were followed every 3 months following the last use of study drug until death or study cutoff, whichever came first.

View Eligibility Criteria

Eligibility Criteria

Inclusion criteria:

Phase 1:

For dose escalation cohorts, participants with confirmed selected CD38+ hematological malignancies as specified below who had progressed on after standard therapy or for whom there was no effective standard therapy (refractory/relapsed participants). B-cell Non-Hodgkin-lymphoma/leukemia (NHL) participants with at least 1 measurable lesion. Multiple myeloma (MM) participants with measurable M-protein serum and/or 24-hour urine. Acute myeloid leukemia (AML) participants, all types except M3 based on French-American-British (FAB) classification. Acute Lymphoblastic Leukemia (B-cell ALL) participants. Chronic lymphocytic leukemia (CLL) participants.
For expansion cohorts, participants with relapsed/refractory MM with measurable M-protein (serum M-protein of >0.5 g/dL and/or urine M-protein of >200 mg (24-hr urine)) or elevated serum free light chains (FLC) >10 mg/dL with abnormal FLC ratio) who had progressed on or after standard therapy that included an Immunomodulatory drug (IMiD) and a proteasome inhibitor and who met the protocol defined criteria for standard risk or high risk.

Phase 2:

Participants had a known diagnosis of multiple myeloma with evidence of measurable disease, and have evidence of disease progression based on International Myeloma Working Group (IMWG) criteria: Serum M-protein ≥1 g/dL, or urine M-protein >=200 mg/24 hours or in the absence of measurable m-protein, serum FLC >=10 mg/dL, and abnormal serum immunoglobulin kappa lambda FLC ratio (<0.26 or >1.65).
Participants who received at least three prior lines of therapy for MM and had treatment with an IMiD (for >=2 cycles or >=2 months of treatment) and a proteasome inhibitor (PI) (for >=2 cycles or >=2 months of treatment) OR participants whose disease was double refractory to an IMiD and a PI. For participants who had received more than 1 type of IMiD and PI, their disease must be refractory to the most recent one.
Participants who had achieved a minimal response or better to at least one prior line of therapy.
Participants who had received an alkylating agent (>=2 cycles or >=2 months) either alone or in combination with other MM treatments.
Stage 2 only: Participants who had evidence of disease progression on or after the most recent prior regimen based on IMWG criteria.

Exclusion criteria:

Phase 1:

Karnofsky performance status <60
Poor bone marrow reserve
Poor organ function
Known intolerance to infused protein products, sucrose, histidine, polysorbate 80 or known hypersensitivity to any of the components of the study therapy that was not amenable to pre-medication with steroids and H2 blockers
Any serious active disease (including clinically significant infection that was chronic, recurrent, or active) or co-morbid condition, which, in the opinion of the investigator, interfered with the safety, the compliance with the study or with the interpretation of the results
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

Phase 2:

Participants with multiple myeloma immunoglobulin M (IgM) subtype
Previous treatment with any anti-CD38 therapy
Participants with concurrent plasma cell leukemia
Participants with known or suspected amyloidosis
Karnofsky performance status <60 (stage 1)/Eastern Cooperative Oncology Group (ECOG) Performance status >2 (stage 2).
Poor bone marrow reserve
Poor organ function
Known intolerance to infused protein products, sucrose, histidine, polysorbate 80 or known hypersensitivity to any of the components of the study therapy that was not amenable to pre-medication with steroids and H2 blockers
Any serious active disease (including clinically significant infection that was chronic, recurrent, or active) or co-morbid condition, which, in the opinion of the investigator, interfered with the safety, the compliance with the study or with the interpretation of the results
Any severe underlying medical conditions including presence of laboratory abnormalities, which impaired the ability to participate in the study or the interpretation of its results

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

Study is for people with:

Multiple Myeloma

Phase:

Phase 1

Estimated Enrollment:

351

Study ID:

NCT01084252

Recruitment Status:

Active, not recruiting

Sponsor:

Sanofi

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There are 57 Locations for this study

See Locations Near You

Investigational Site Number 840003
Scottsdale Arizona, 85054, United States
Investigational Site Number 840005
San Francisco California, 94117, United States
Investigational Site Number 840009
Atlanta Georgia, 30322, United States
Investigational Site Number 840010
Chicago Illinois, 60637, United States
Investigational Site Number 840022
Ann Arbor Michigan, 48109, United States
Investigational Site Number 840027
Detroit Michigan, 48201, United States
Investigational Site Number 840018
Rochester Minnesota, 55905, United States
Investigational Site Number 840013
Saint Louis Missouri, 63110, United States
Investigational Site Number 840011
Hackensack New Jersey, 07601, United States
Investigational Site Number 840014
New York New York, 10021, United States
Investigational Site Number 840016
Durham North Carolina, 27707, United States
Investigational Site Number 840004
Cincinnati Ohio, 45267, United States
Investigational Site Number 840001
Nashville Tennessee, 37232, United States
Investigational Site Number 840002
Salt Lake City Utah, 84112, United States
Investigational Site Number 840012
Seattle Washington, 98109, United States
Investigational Site Number 840017
Milwaukee Wisconsin, 53226, United States
Investigational Site Number 032002
Caba , C1181, Argentina
Investigational Site Number 032003
Capital Federal , C1425, Argentina
Investigational Site Number 032001
Ciudad De Buenos Aires , C1426, Argentina
Investigational Site Number 056001
Antwerpen , 2060, Belgium
Investigational Site Number 076001
Barretos , 14784, Brazil
Investigational Site Number 076003
Porto Alegre , 90470, Brazil
Investigational Site Number 076004
Rio De Janeiro , 22793, Brazil
Investigational Site Number 076002
Sao Paulo , 04537, Brazil
Investigational Site Number 152001
Temuco , 48104, Chile
Investigational Site Number 246001
Helsinki , 00029, Finland
Investigational Site Number 246002
Turku , 20521, Finland
Investigational Site Number 250003
Nantes Cedex 01 , 44093, France
Investigational Site Number 250004
Pierre Benite , 69310, France
Investigational Site Number 250001
Toulouse Cedex 9 , 31059, France
Investigational Site Number 300001
Athens , 11528, Greece
Investigational Site Number 376004
Jerusalem , 91120, Israel
Investigational Site Number 376002
Tel Hashomer , 52621, Israel
Investigational Site Number 380001
Bologna , 40138, Italy
Investigational Site Number 380002
Torino , 10126, Italy
Investigational Site Number 484001
Monterrey , 64460, Mexico
Investigational Site Number 484003
San Luis Potosi , 78419, Mexico
Investigational Site Number 604001
Arequipa , , Peru
Investigational Site Number 604002
Lima , LIMA , Peru
Investigational Site Number 643002
Moscow , 12528, Russian Federation
Investigational Site Number 643003
Novosibirsk , 63008, Russian Federation
Investigational Site Number 643001
Petrozavodsk , 18501, Russian Federation
Investigational Site Number 643004
Saint-Petersburg , 19429, Russian Federation
Investigational Site Number 724007
Badalona , 08916, Spain
Investigational Site Number 724005
Barcelona , 08036, Spain
Investigational Site Number 724004
Madrid , 28041, Spain
Investigational Site Number 724002
Pamplona , 31008, Spain
Investigational Site Number 724001
Salamanca , 37007, Spain
Investigational Site Number 724008
Sevilla , 41013, Spain
Investigational Site Number 724006
Valencia , 46017, Spain
Investigational Site Number 792002
Ankara , 06200, Turkey
Investigational Site Number 792005
Ankara , 06500, Turkey
Investigational Site Number 792001
İstanbul , , Turkey
Investigational Site Number 792004
Samsun , 55139, Turkey
Investigational Site Number 804001
Kyiv , 04112, Ukraine
Investigational Site Number 804004
Vinnitsya , 21018, Ukraine
Investigational Site Number 804002
Zaporizhzhya , 69600, Ukraine
Investigational Site Number 826001
Nottingham , NG5 1, United Kingdom
Investigational Site Number 826002
Southampton , SO16 , United Kingdom

How clear is this clinincal trial information?

Study is for people with:

Multiple Myeloma

Phase:

Phase 1

Estimated Enrollment:

351

Study ID:

NCT01084252

Recruitment Status:

Active, not recruiting

Sponsor:


Sanofi

How clear is this clinincal trial information?

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