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

Primary Purpose

Hematological Malignancy

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Isatuximab SAR650984
Dexamethasone
Dexamethasone
Sponsored by
Sanofi
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hematological Malignancy focused on measuring Anti-CD38 monoclonal antibody

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Investigational Site Number 840003
  • Investigational Site Number 840005
  • Investigational Site Number 840009
  • Investigational Site Number 840010
  • Investigational Site Number 840022
  • Investigational Site Number 840027
  • Investigational Site Number 840018
  • Investigational Site Number 840013
  • Investigational Site Number 840011
  • Investigational Site Number 840014
  • Investigational Site Number 840016
  • Investigational Site Number 840004
  • Investigational Site Number 840001
  • Investigational Site Number 840002
  • Investigational Site Number 840012
  • Investigational Site Number 840017
  • Investigational Site Number 032002
  • Investigational Site Number 032003
  • Investigational Site Number 032001
  • Investigational Site Number 056001
  • Investigational Site Number 076001
  • Investigational Site Number 076003
  • Investigational Site Number 076004
  • Investigational Site Number 076002
  • Investigational Site Number 152001
  • Investigational Site Number 246001
  • Investigational Site Number 246002
  • Investigational Site Number 250003
  • Investigational Site Number 250004
  • Investigational Site Number 250001
  • Investigational Site Number 300001
  • Investigational Site Number 376004
  • Investigational Site Number 376002
  • Investigational Site Number 380001
  • Investigational Site Number 380002
  • Investigational Site Number 484001
  • Investigational Site Number 484003
  • Investigational Site Number 604001
  • Investigational Site Number 604002
  • Investigational Site Number 643002
  • Investigational Site Number 643003
  • Investigational Site Number 643001
  • Investigational Site Number 643004
  • Investigational Site Number 724007
  • Investigational Site Number 724005
  • Investigational Site Number 724004
  • Investigational Site Number 724002
  • Investigational Site Number 724001
  • Investigational Site Number 724008
  • Investigational Site Number 724006
  • Investigational Site Number 792002
  • Investigational Site Number 792005
  • Investigational Site Number 792001
  • Investigational Site Number 792004
  • Investigational Site Number 804001
  • Investigational Site Number 804004
  • Investigational Site Number 804002
  • Investigational Site Number 826001
  • Investigational Site Number 826002

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm 13

Arm 14

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Phase 1:Isatuximab <=1 mg/kg Q2W

Phase 1: Isatuximab 3mg/kg Q2W

Phase 1: Isatuximab 5 mg/kg Q2W

Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma)

Phase 1:Isatuximab (CD38 + HM and High Risk Multiple Myeloma)

Phase 1: Isatuximab 10 mg/kg QW

Phase 1: Isatuximab 20 mg/kg Q2W

Phase 1: Isatuximab 20 mg/kg QW

Phase 2 Stage 1a: Isatuximab 3 mg/kg Q2W

Phase 2 Stage 1a: Isatuximab 10 mg/kg Q2W

Phase2 Stage1a:Isatuximab 10mg/kg Q2W; Then Q4W

Phase 2 Stage 1b: Isatuximab 20mg/kg QW and Then Q2W

Phase 2 Stage 2: Isatuximab Alone

Phase 2 Stage 2: Isatuximab + Dexamethasone

Arm Description

Participants with CD38+ hematological malignancies (HM), received Isatuximab at any one of the dose less than or equal to (<=) 1 milligram per kilogram (mg/kg) (i.e. either 0.0001 mg/kg or 0.001 mg/kg or 0.01 mg/kg or 0.03 mg/kg or 0.1 mg/kg or 0.3 mg/kg or 1 mg/kg) as intravenous (IV) infusion on Day 1 of each 14-day treatment cycle until occurrence of unacceptable toxicity, disease progression, death, consent withdrawal by participant, investigator's decision, and/or availability of study drug (maximum exposure: 120 weeks).

Participants with CD38+ HM, received Isatuximab 3 mg/kg, as IV infusion on Day 1 of each 14-day treatment cycle until occurrence of unacceptable toxicity, disease progression, death, consent withdrawal, investigator's decision, and/or availability of study drug (maximum exposure: 120 weeks).

Participants with CD38+ HM, received Isatuximab 5 mg/kg, as IV infusion on Day 1 of each 14-day treatment cycle until occurrence of unacceptable toxicity, disease progression, death, consent withdrawal, investigator's decision, and/or availability of study drug (maximum exposure: 120 weeks).

Participants with CD38+ HM along with participants with standard risk multiple myeloma were included this arm and, received Isatuximab 10 mg/kg, as IV infusion on Day 1 of each 14-day treatment cycle until occurrence of unacceptable toxicity, disease progression, death, consent withdrawal, investigator's decision, and/or availability of study drug (maximum exposure: 120 weeks).

Participants with CD38+ HM along with participants with high risk multiple myeloma, received Isatuximab 10 mg/kg, as IV infusion on Day 1 of each 14-day treatment cycle until occurrence of unacceptable toxicity, disease progression, death, consent withdrawal, investigator's decision, and/or availability of study drug (maximum exposure: 120 weeks).

Participants with CD38+ HM, received Isatuximab 10 mg/kg, as IV infusion QW, i.e. on Day 1 and 8 of each 14-day treatment cycle until occurrence of unacceptable toxicity, disease progression, death, consent withdrawal, investigator's decision, and/or availability of study drug (maximum exposure: 120 weeks).

Participants with CD38+ HM, received Isatuximab 20 mg/kg, as IV infusion on Day 1 of each 14-day treatment cycle until occurrence of unacceptable toxicity, disease progression, death, consent withdrawal, investigator's decision, and/or availability of study drug (maximum exposure: 120 weeks).

Participants with CD38+ HM, received Isatuximab 20 mg/kg, as IV infusion QW, i.e. on Day 1 and 8 of each 14-day treatment cycle until occurrence of unacceptable toxicity, disease progression, death, consent withdrawal, investigator's decision, and/or availability of study drug (maximum exposure: 120 weeks).

Participants with multiple Myeloma received Isatuximab 3 mg/kg, as IV infusion on Day 1 and Day 15 of each 28-day cycle until unacceptable adverse event (AE), disease progression, poor compliance to the study protocol, study termination or lost to follow up (maximum exposure: 77 weeks).

Participants with multiple Myeloma received Isatuximab 10 mg/kg, as IV infusion on Day 1 and Day 15 of each 28-day cycle until unacceptable AE, disease progression, poor compliance to the study protocol, study termination or lost to follow up (maximum exposure: 77 weeks).

Participants with multiple Myeloma received Isatuximab 10 mg/kg, as IV infusion Q2W, i.e. on Day 1 and Day 15 of Cycle 1 and 2 (each cycle 28 days), then every 4 week (Q4W), i.e. on Day 1 of each 28-days cycle until unacceptable AE, disease progression, poor compliance to the study protocol, study termination or lost to follow up (maximum exposure: 77 weeks).

Participants with multiple Myeloma received Isatuximab 20 mg/kg, as IV infusion QW, i.e. on Day 1, 8, 15 and 22 of Cycle 1 and 2 (each cycle 28 days), then Q2W, i.e. on Day 1 and Day 15 of each 28-days cycle until unacceptable AE, disease progression, poor compliance to the study protocol, study termination or lost to follow up (maximum exposure: 53 weeks).

Participants with relapsed or relapsed/refractory multiple myeloma (RRMM), received Isatuximab 20 mg/kg, as IV infusion on Day 1, 8, 15 and Day 22 of Cycle 1 (28 days) and then on Day 1 and 15 of each subsequent 28-day cycles until unacceptable AE, disease progression, poor compliance to the study protocol, study termination, lost to follow up or investigator's decision maximum exposure: 97 weeks).

Participants with relapsed or RRMM, received Isatuximab 20 mg/kg, as IV infusion on Day 1, 8, 15 and Day 22 of Cycle 1 (28 days) and then on Day 1 and 15 of each subsequent 28-day cycles along with dexamethasone: tablet or as IV infusion (40 mg/day for less than [<] 75 years of age; 20 mg/day [greater than or equal to [>=] for 75 years of age) on Days 1, 8, 15 and 22 of each 28 days cycle until unacceptable AE, disease progression, poor compliance to the study protocol, study termination, lost to follow up or investigator's decision (maximum exposure: 97 weeks).

Outcomes

Primary Outcome Measures

Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs)
DLTs were assessed using the national cancer institute common terminology criteria for adverse events (NCI-CTCAE) version 4.03. DLTs were defined as any Grade 3 or higher non-hematological toxicity (with the exception of allergic reaction/hypersensitivity), Grade 4 neutropenia and/or Grade 4 thrombocytopenia lasting longer than 5 days, attributed to isatuximab. Any other toxicity that the Investigator and the Sponsor deemed to be dose-limiting, regardless of the grade, was also considered as DLT.
Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily have to have a causal relationship with the treatment. TEAEs were defined as AEs that developed or worsened during the on-treatment period which was defined as the period from the time of first dose of study treatment until 30 days after the last dose of study treatment.
Phase 2 Stage 1: Percentage of Participants With Overall Response (OR) According to International Myeloma Working Group (IMWG) Uniform Response Criteria
OR defined as participants with stringent complete response (sCR) or complete response (CR) or very good partial response (VGPR) or partial response (PR) . Based on IMWG, CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and <=5% plasma cells in bone marrow; sCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or >=90% reduction in serum M-protein and urine M-protein level <100 mg/24 hours; PR: >=50% reduction of serum M-Protein and reduction in urinary M-protein by >=90% or to <200 mg/24 hours; >=50% decrease in the difference between involved and uninvolved FLC levels in place of the M-protein criteria or a >=50% reduction in plasma cells in place of M-protein if present at baseline.
Phase 2 Stage 2: Percentage of Participants With Overall Response According to Updated IMWG Response Criteria
OR: participants with sCR or CR or VGPR or PR. As per updated IMWG, CR: Negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and <=5% plasma cells in bone marrow; normal FLC ratio of 0.26-1.65 in participants with only FLC disease; sCR: CR and normal FLC ratio and no clonal cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or >=90% reduction in serum M-protein and urine M-protein level <100 mg/24 hours, >90% decrease in the difference between involved and uninvolved FLC levels; PR: >=50% reduction of serum M-Protein and reduction in urinary M-protein by >=90% or to <200 mg/24 hours; >=50% decrease in the difference between involved and uninvolved FLC levels in place of M-protein criteria or >=50% reduction in plasma cells in place of M-protein if present at baseline.

Secondary Outcome Measures

Pharmacokinetic (PK) Assessment: Phase 1: Plasma Concentration of Isatuximab Observed at the End of an Intravenous Infusion (Ceoi)
Ceoi was defined as the plasma concentration of Isatuximab at end of infusion. Data for this outcome measure was planned to be collected and analyzed separately for dose 0.3 mg/kg, 1 mg/kg and not for 0.0001, 0.001, 0.01, 0.03 and 0.1 dose levels (reported under one arm, i.e. Phase 1: Isatuximab <=1mg/kg in participant flow). Analysis was performed on PK population: participants who gave informed consent, received at least one dose (even if incomplete) of isatuximab, had an assessable PK parameter.
PK Assessment: Phase 1: Maximum Observed Plasma Concentration (Cmax) of Isatuximab
Data for this outcome measure was planned to be collected and analyzed separately for dose 0.3 mg/kg, 1 mg/kg and not for 0.0001, 0.001, 0.01, 0.03 and 0.1 dose levels (reported under one arm, i.e. Phase 1: Isatuximab <=1mg/kg in participant flow). Analysis was performed on PK population.
PK Assessment: Phase 1: Time to Reach Maximum Plasma Concentration Observed (Tmax) of Isatuximab
Data for this outcome measure was planned to be collected and analyzed separately for dose 0.3 mg/kg, 1 mg/kg and not for 0.0001, 0.001, 0.01, 0.03 and 0.1 dose levels (reported under one arm, i.e. Phase 1: Isatuximab <=1mg/kg in participant flow). Analysis was performed on PK population.
PK Assessment: Phase 1: Plasma Concentration of Isatuximab at Week 1, 2 and 3
Data for this outcome measure was planned to be collected and analyzed only for dose 1 mg/kg and not for 0.0001, 0.001, 0.01, 0.03, 0.1 and 0.3 mg/kg dose levels (reported under one arm, i.e. Phase 1: Isatuximab <=1mg/kg in participant flow).
PK Assessment: Phase 1: Predicted Cumulative Area Under the Plasma Concentration Curve (AUC) of Isatuximab Over the First Week (0-168 Hours) (AUC1W)
Data for this outcome measure was planned to be collected and analyzed only for dose 1 mg/kg and not for 0.0001, 0.001, 0.01, 0.03, 0.1 and 0.3 mg/kg dose levels (reported under one arm, i.e. Phase 1: Isatuximab <=1mg/kg in participant flow).
PK Assessment: Phase 1: Predicted Cumulative Area Under the Plasma Concentration Curve (AUC) of Isatuximab Over the First 2 Weeks (0-336 Hours) (AUC2W)
Data for this outcome measure was planned to be collected and analyzed only for dose 1 mg/kg and not for 0.0001, 0.001, 0.01, 0.03, 0.1 and 0.3 mg/kg dose levels (reported under one arm, i.e. Phase 1: Isatuximab <=1mg/kg in participant flow).
Pharmacodynamic (PD) Assessment: Phase 1: Change From Baseline in Serum/Plasma Markers
Serum/plasma markers included: tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1-β), interleukin 6 (IL-6) and interferon-gamma (IFN-Gamma). Due to change in planned analysis, data for high-sensitivity C-reactive protein (hs-CRP) and CD38 was not collected and analyzed.
Immunogenicity Assessment: Phase 1: Number of Participants With Treatment-Emergent And Treatment-Boosted Anti-drug Antibodies (ADA) Response
ADA response was categorized as: treatment induced and treatment boosted response. Treatment-induced ADA was defined as ADA that developed at any time during the ADA on-study observation period (defined as the time from the first isatuximab administration until end of Phase 1) in participants without preexisting ADA (defined as: ADA that were present in samples drawn before treatment), including participants without pre-treatment (before treatment) samples. Treatment boosted ADA was defined as pre-existing ADA that increased at least 2 titer steps between pre-treatment (before treatment) and post-treatment.
Clinical Assessment: Phase 1: Percentage of Participants With Overall Response and Clinical Benefit: Assessed Using European Society for Blood and Marrow Transplantation (EBMT) Criteria
OR defined as participants with complete response (CR) or partial response (PR) as best overall response (BOR). Clinical benefit: participants with minimal response (MR) or better as BOR. BOR: best sequential response from start of treatment through the entire study excluding any time point following start of other treatment. CR: negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas, <5% plasma cells in bone marrow aspirates, no increase in size or number of lytic bone lesions. PR: >=50% reduction of serum M-protein, reduction in 24 h urinary M-protein by >=90% or <200mg, >=50% reduction in size/number of soft tissue plasmacytomas, no increase in size or number of lytic bone lesions. MR: 25 to 49% reduction in serum M-protein, 50-89% reduction in 24h urine M-protein, 25-49% reduction in size of soft tissue plasmacytomas, no increase in size or number of lytic bone lesions.
Clinical Assessment: Phase 1: Duration of Response (DOR)
DOR: time from first response (PR or better) to first documented tumor progression/death. Progression as per EBMT: >25% increase in serum monoclonal paraprotein level, which must also be an absolute increase of >= 5 g/l: confirmed by >=1 repeated investigation; >25% increase in 24h urinary light chain excretion, which must also be an absolute increase of >=200 mg/24 h:confirmed by >=1 repeated investigation; >25% increase in plasma cells in a bone marrow aspirate/on trephine biopsy, which must also be an absolute increase of >= 10%; definite increase in size of existing bone lesions/soft tissue plasmacytomas; development of new bone lesions/soft tissue plasmacytomas; development of hypercalcemia (corrected serum calcium >11·5 mg/dl or 2·8 mmol/l) not attributable to any other cause. PR: >=50% reduction of serum M-protein, reduction in 24h urinary M-protein by >=90% or <200mg, >=50% reduction in size/number of soft tissue plasmacytomas, no increase in size/number of lytic bone lesions.
Clinical Assessment: Phase 1: Time to First Response (TTR)
TTR was defined as the time from first dose of isatuximab to first response (PR or better). PR: >=50% reduction of serum M-protein, reduction in 24 h urinary M-protein by >=90% or <200mg, >=50% reduction in size/number of soft tissue plasmacytomas, no increase in size or number of lytic bone lesions.
Clinical Assessment: Phase 1: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) (Karnofsky Performance Status)-Shift From Baseline Value to Best Value During Treatment
ECOG performance status was measured on a 4 point scale to assess participant's performance status. 0=Normal, fully functional; 1=Fatigue without significant decrease in daily activity; 2=Fatigue with significant impairment of daily activities or bed rest <50% of waking hours; 3=Bed rest/sitting >50% of waking hours; 4=Bedridden or unable to care for self, where lower score indicated good performance status. Number of participants with Baseline ECOG PS score and corresponding changes to the best values (categorized as: Baseline ECOG 1, During Treatment ECOG 0; Baseline ECOG 2, During Treatment ECOG 0; Baseline ECOG 2, During Treatment ECOG 1) are reported.
Clinical Assessment: Phase 1: Number of Participants With Eastern Cooperative Oncology Group Performance Status (Karnofsky Performance Status)-Shift From Baseline Value to Worst Value During Treatment
ECOG performance status was measured on a 4 point scale to assess participant's performance status. 0=Normal, fully functional; 1=Fatigue without significant decrease in daily activity; 2=Fatigue with significant impairment of daily activities or bed rest <50% of waking hours; 3=Bed rest/sitting>50% of waking hours; 4=Bedridden or unable to care for self, where higher score indicated worst performance status. Number of participants with Baseline ECOG PS score and corresponding changes to the worst values (categorized as: Baseline ECOG 0, During Treatment ECOG 1; Baseline ECOG 2, During Treatment ECOG 1; Baseline ECOG 0, During Treatment ECOG 2; Baseline ECOG 1, During Treatment ECOG 2; Baseline ECOG 0, During Treatment ECOG 3; Baseline ECOG 1, During Treatment ECOG 3; Baseline ECOG 2, During Treatment ECOG 3) are reported.
Phase 2 Stage 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily have to have a causal relationship with the treatment. TEAEs were defined as AEs that developed or worsened during the on-treatment period which was defined as the period from the time of first dose of study treatment until 30 days after the last dose of study treatment.
Phase 2 Stage 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily have to have a causal relationship with the treatment. TEAEs were defined as AEs that developed or worsened during the on-treatment period which was defined as the period from the time of first dose of study treatment until 30 days after the last dose of study treatment.
Phase 2 Stage 1: Duration of Response
DOR:Time from date of 1st IAC determined response (>= PR) that was subsequently confirmed, to date of first IAC determined PD/death, whichever happened earlier. updated IMWG criteria- PR:>=50% decrease in difference between involved and uninvolved FLC levels in place of M-protein criteria or a >=50% reduction in plasma cells in place of M-protein if baseline was ≥30%. If present at baseline a >=50% reduction in size of soft tissue plasmacytomas; PD: Increase of 25% from lowest response value in any of following: Serum M-protein >=0.5 g/dL absolute increase and/or urine M-protein >=200 mg/24 hours absolute increase and/or >10 mg/dL absolute increase in difference between involved and uninvolved FLC levels, >=10% bone marrow plasma cells (PCs), development of new bone lesions/soft tissue plasmacytomas or definite increase in size of existing bone lesions/soft tissue plasmacytomas, development of hypercalcemia (corrected serum calcium >11·5 mg/dl) attributed to PC proliferation disorder.
Phase 2 Stage 2: Duration of Response
DOR: Time from date of 1st IAC determined response (>= PR) that was subsequently confirmed, to date of 1st IAC determined PD or death, whichever happened earlier. As per updated IMWG criteria-PR: ≥50% reduction of serum M-Protein and reduction in urinary M-protein by ≥90% or to <200 mg/24 hours. ≥50% decrease in difference between involved and uninvolved FLC levels in place of M-protein criteria or ≥50% reduction in plasma cells in place of M-protein if baseline was ≥30%. If present at baseline ≥50% reduction in size of soft tissue plasmacytomas; PD: Increase of >25% from lowest response value in any one of following: Serum M-component (absolute increase must be >0.5 g/dL)4 and/or Urine M-component (absolute increase must be >200 mg/24 h) and/or >10 mg/dL absolute increase in difference between involved and uninvolved FLC levels, >=10% bone marrow plasma cell, development of hypercalcemia (corrected serum calcium >11.5 mg/dL) attributed solely to plasma cell proliferative disorder.
Phase 2 Stage 1: Percentage of Participants With Clinical Benefit
Clinical benefit: participants with sCR, CR, VGPR, PR or MR as per IMWG criteria, determined by IAC. CR: negative immunofixation on serum & urine, disappearance of any soft tissue plasmacytomas,<5% PCs in bone marrow aspirates. sCR: CR + normal FLC ratio (0.26-1.65), absence of clonal cells in bone marrow biopsy. VGPR: serum & urine M-component detectable by immunofixation, not on electrophoresis/,>=90% reduction in serum M-component plus urine M-component level <100mg/24hours; PR: ≥50% reduction of serum M-Protein and reduction in urinary M-protein by ≥90% or to <200 mg/24 hours, ≥50% decrease in the difference between involved and uninvolved FLC levels in place of the M-protein criteria or a ≥50% reduction in plasma cells in place of M-protein if baseline was ≥30%. If present at baseline, ≥50% size reduction in soft tissue plasmacytomas. MR:>=25 but <49% reduction in serum M-protein, reduction in 24h urine M-protein by 50-89%, 25-49% size reduction in soft tissue plasmacytomas.
Phase 2 Stage 2: Percentage of Participants With Clinical Benefit
Clinical benefit:participants with sCR, CR, VGPR, PR or MR, per IMWG criteria, determined by IAC. CR:negative immunofixation on serum & urine, disappearance of any soft tissue plasmacytomas,<5% plasma cells in bone marrow aspirates,normal FLC ratio(0.26-1.65) in participants with only FLC disease.sCR:CR+normal FLC ratio, absence of clonal cells in bone marrow biopsy.VGPR:serum & urine M-component detectable by immunofixation, not on electrophoresis/,>=90% reduction in serum M-component plus urine M-component level <100mg/24h/,>=90% decrease in difference between involved and uninvolved FLC levels; PR:>=50% reduction of serum M-protein, reduction in 24h urinary M-protein by >=90%/<200mg/24h,>50% decrease in difference between involved and uninvolved FLC in place of M-protein criteria, >=50% reduction in size/number of soft tissue plasmacytomas. MR:>=25 but <49% reduction in serum M-protein,reduction in 24h urine M-protein by 50-89%, 25-49% reduction in size of soft tissue plasmacytomas
Phase 2 Stage 1: Progression Free Survival (PFS)
PFS was defined as the time interval from the date of first isatuximab administration to the date of the first IAC-confirmed disease progression (PD) or date of death due to any cause, whichever came first. As per IMWG criteria, PD: Increase of > 25% from lowest response value in any one or more of the following: Serum M-component and/or (the absolute increase must be > 0.5 g/dL), Urine M-component and/or (the absolute increase must be > 200 mg/24 h), > 10mg/dL decrease in the difference between involved and uninvolved FLC levels in place of the M-protein criteria, >10% absolute percentage of bone marrow plasma cell, definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas, development of hypercalcemia (corrected serum calcium > 11.5 mg/dL or 2.65 mmol/L) that attributed solely to the plasma cell proliferative disorder. Analysis was performed by Kaplan-Meier method.
Phase 2 Stage 2: Progression Free Survival
PFS was defined as the time interval from the date of first isatuximab administration to the date of the first IAC-confirmed disease progression or the date of death due to any cause, whichever came first. As per IMWG criteria, PD: Increase of >25% from lowest response value in any one of the following: Serum M-component (the absolute increase must be >0.5 g/dL)4 and/or Urine M-component (the absolute increase must be >200 mg/24 h) and/or >10 mg/dL decrease in the difference between involved and uninvolved FLC levels in place of the M-protein criteria, ≥10% bone marrow plasma cell, development of hypercalcemia (corrected serum calcium >11.5 mg/dL) attributed solely to the plasma cell proliferative disorder. Analysis was performed by Kaplan-Meier method.
Phase 2 Stage 1: Overall Survival (OS)
OS was defined as the time interval from the date of first Isatuximab administration to death from any cause. Analysis was performed by Kaplan-Meier method.
Phase 2 Stage 2: Overall Survival
OS was defined as the time interval from the date of first Isatuximab administration to death from any cause. Analysis was performed by Kaplan-Meier method.
Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status
EORTC-QLQ-C30 is a cancer-specific instrument with 30 questions for evaluation of new chemotherapy and provides an assessment of participant reported outcome dimensions. First 28 questions used 4-point scale (1=not at all,2=a little,3=quite a bit,4=very much) for evaluating 5 functional scales (physical, role, emotional, cognitive, social), 3 symptom scales (fatigue, nausea/vomiting, pain) & other single items. For each item, high score = high level of symptomatology/problem. Last 2 questions represented participant's assessment of overall health & quality of life, coded on 7-point scale (1=very poor to 7=excellent). EORTC QLQ-C30 observed values and change from baseline for global health status (scoring of questions 29 & 30) and 5 functional scales, 3 symptom scales and other single items (scoring of questions 1 to 28). Answers were converted into grading scale, with values between 0 and 100. A high score represented a favorable outcome with a best quality of life for participant.
Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score
EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in participants with MM. It has 4 subscales: body image, future perspective), and 2 symptoms scales (disease symptoms and side-effects of treatment). Disease symptoms subscale used 4-point scale ranged from 1= 'Not at All' to 4= 'Very Much'. Scores were averaged, and transformed to 0 -100 scale, where higher scores = more symptoms and lower health-related quality of life (HRQL) and lower score = less symptoms and more HRQL.
Phase 2 Stage 1: Change From Baseline in Euro Quality of Life 5 Dimension (EQ-5D) Generic Health Status - Visual Analogue Scale Scores
EQ-5D was a standardized HRQL questionnaire consisting of EQ-5D descriptive system and Visual Analogue Scale (VAS). EQ-5D VAS was used to record a participant's rating for his/her current health-related quality of life state and captured on a vertical VAS (0-100), where 0 = worst imaginable health state and 100 = best imaginable health state.
Pharmacokinetic Assessment: Phase 2 Stage 2: Area Under the Plasma Concentration Versus Time Curve of Isatuximab Over 1 Week Interval
Pharmacokinetic Assessment: Phase 2 Stage 2: Area Under the Plasma Concentration Versus Time Curve of Isatuximab Over 2 Weeks Interval
Pharmacokinetic Assessment: Phase 2 Stage 2: Area Under the Plasma Concentration Versus Time Curve of Isatuximab Over 4 Weeks Interval
Pharmacokinetic Assessment: Phase 2 Stage 2: Plasma Concentration of Isatuximab Before Treatment Administration (Ctrough)
Pharmacokinetic Assessment: Phase 2 Stage 2: Accumulation Ratio of Isatuximab Based on Ctrough
Ctrough is the plasma concentration observed before treatment administration. For 1st category, the accumulation ratio was calculated by dividing Ctrough value of Cycle 2 Day 1 by Cycle 1 Day 8 and for second category, accumulation ratio was calculated by dividing Ctrough value of Cycle 4 Day 1 by Cycle 1 Day 8.
Immunogenicity Assessment: Phase 2 Stage 2: Number of Participants With Anti-drug Antibodies to Isatuximab
ADA response was categorized as: treatment induced and treatment boosted response. Treatment-induced ADA was defined as ADA that developed at any time during the ADA on-study observation period (defined as the time from the first isatuximab administration until end of Phase 2 Stage 2) in participants without preexisting ADA (defined as: ADA that were present in samples drawn before treatment), including participants without pre-treatment (before treatment) samples. Treatment boosted ADA was defined as pre-existing ADA that increased at least 2 titer steps between pre-treatment (before treatment) and post-treatment.

Full Information

First Posted
March 9, 2010
Last Updated
October 5, 2023
Sponsor
Sanofi
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1. Study Identification

Unique Protocol Identification Number
NCT01084252
Brief Title
Phase 1/2 Dose Escalation and Efficacy Study of Anti-CD38 Monoclonal Antibody in Patients With Selected CD38+ Hematological Malignancies
Official Title
A Phase I/2 Dose Escalation Safety, Pharmacokinetic and Efficacy Study of Multiple Intravenous Administrations of a Humanized Monoclonal Antibody (SAR650984) Against CD38 in Patients With Selected CD38+ Hematological Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Completed
Study Start Date
June 10, 2010 (Actual)
Primary Completion Date
December 21, 2018 (Actual)
Study Completion Date
July 13, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Primary Objective: Phase 1: To determine the maximum tolerated dose (MTD)/maximum administered dose (MAD) of SAR650984 (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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematological Malignancy
Keywords
Anti-CD38 monoclonal antibody

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
351 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Phase 1:Isatuximab <=1 mg/kg Q2W
Arm Type
Experimental
Arm Description
Participants with CD38+ hematological malignancies (HM), received Isatuximab at any one of the dose less than or equal to (<=) 1 milligram per kilogram (mg/kg) (i.e. either 0.0001 mg/kg or 0.001 mg/kg or 0.01 mg/kg or 0.03 mg/kg or 0.1 mg/kg or 0.3 mg/kg or 1 mg/kg) as intravenous (IV) infusion on Day 1 of each 14-day treatment cycle until occurrence of unacceptable toxicity, disease progression, death, consent withdrawal by participant, investigator's decision, and/or availability of study drug (maximum exposure: 120 weeks).
Arm Title
Phase 1: Isatuximab 3mg/kg Q2W
Arm Type
Experimental
Arm Description
Participants with CD38+ HM, received Isatuximab 3 mg/kg, as IV infusion on Day 1 of each 14-day treatment cycle until occurrence of unacceptable toxicity, disease progression, death, consent withdrawal, investigator's decision, and/or availability of study drug (maximum exposure: 120 weeks).
Arm Title
Phase 1: Isatuximab 5 mg/kg Q2W
Arm Type
Experimental
Arm Description
Participants with CD38+ HM, received Isatuximab 5 mg/kg, as IV infusion on Day 1 of each 14-day treatment cycle until occurrence of unacceptable toxicity, disease progression, death, consent withdrawal, investigator's decision, and/or availability of study drug (maximum exposure: 120 weeks).
Arm Title
Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma)
Arm Type
Experimental
Arm Description
Participants with CD38+ HM along with participants with standard risk multiple myeloma were included this arm and, received Isatuximab 10 mg/kg, as IV infusion on Day 1 of each 14-day treatment cycle until occurrence of unacceptable toxicity, disease progression, death, consent withdrawal, investigator's decision, and/or availability of study drug (maximum exposure: 120 weeks).
Arm Title
Phase 1:Isatuximab (CD38 + HM and High Risk Multiple Myeloma)
Arm Type
Experimental
Arm Description
Participants with CD38+ HM along with participants with high risk multiple myeloma, received Isatuximab 10 mg/kg, as IV infusion on Day 1 of each 14-day treatment cycle until occurrence of unacceptable toxicity, disease progression, death, consent withdrawal, investigator's decision, and/or availability of study drug (maximum exposure: 120 weeks).
Arm Title
Phase 1: Isatuximab 10 mg/kg QW
Arm Type
Experimental
Arm Description
Participants with CD38+ HM, received Isatuximab 10 mg/kg, as IV infusion QW, i.e. on Day 1 and 8 of each 14-day treatment cycle until occurrence of unacceptable toxicity, disease progression, death, consent withdrawal, investigator's decision, and/or availability of study drug (maximum exposure: 120 weeks).
Arm Title
Phase 1: Isatuximab 20 mg/kg Q2W
Arm Type
Experimental
Arm Description
Participants with CD38+ HM, received Isatuximab 20 mg/kg, as IV infusion on Day 1 of each 14-day treatment cycle until occurrence of unacceptable toxicity, disease progression, death, consent withdrawal, investigator's decision, and/or availability of study drug (maximum exposure: 120 weeks).
Arm Title
Phase 1: Isatuximab 20 mg/kg QW
Arm Type
Experimental
Arm Description
Participants with CD38+ HM, received Isatuximab 20 mg/kg, as IV infusion QW, i.e. on Day 1 and 8 of each 14-day treatment cycle until occurrence of unacceptable toxicity, disease progression, death, consent withdrawal, investigator's decision, and/or availability of study drug (maximum exposure: 120 weeks).
Arm Title
Phase 2 Stage 1a: Isatuximab 3 mg/kg Q2W
Arm Type
Experimental
Arm Description
Participants with multiple Myeloma received Isatuximab 3 mg/kg, as IV infusion on Day 1 and Day 15 of each 28-day cycle until unacceptable adverse event (AE), disease progression, poor compliance to the study protocol, study termination or lost to follow up (maximum exposure: 77 weeks).
Arm Title
Phase 2 Stage 1a: Isatuximab 10 mg/kg Q2W
Arm Type
Experimental
Arm Description
Participants with multiple Myeloma received Isatuximab 10 mg/kg, as IV infusion on Day 1 and Day 15 of each 28-day cycle until unacceptable AE, disease progression, poor compliance to the study protocol, study termination or lost to follow up (maximum exposure: 77 weeks).
Arm Title
Phase2 Stage1a:Isatuximab 10mg/kg Q2W; Then Q4W
Arm Type
Experimental
Arm Description
Participants with multiple Myeloma received Isatuximab 10 mg/kg, as IV infusion Q2W, i.e. on Day 1 and Day 15 of Cycle 1 and 2 (each cycle 28 days), then every 4 week (Q4W), i.e. on Day 1 of each 28-days cycle until unacceptable AE, disease progression, poor compliance to the study protocol, study termination or lost to follow up (maximum exposure: 77 weeks).
Arm Title
Phase 2 Stage 1b: Isatuximab 20mg/kg QW and Then Q2W
Arm Type
Experimental
Arm Description
Participants with multiple Myeloma received Isatuximab 20 mg/kg, as IV infusion QW, i.e. on Day 1, 8, 15 and 22 of Cycle 1 and 2 (each cycle 28 days), then Q2W, i.e. on Day 1 and Day 15 of each 28-days cycle until unacceptable AE, disease progression, poor compliance to the study protocol, study termination or lost to follow up (maximum exposure: 53 weeks).
Arm Title
Phase 2 Stage 2: Isatuximab Alone
Arm Type
Experimental
Arm Description
Participants with relapsed or relapsed/refractory multiple myeloma (RRMM), received Isatuximab 20 mg/kg, as IV infusion on Day 1, 8, 15 and Day 22 of Cycle 1 (28 days) and then on Day 1 and 15 of each subsequent 28-day cycles until unacceptable AE, disease progression, poor compliance to the study protocol, study termination, lost to follow up or investigator's decision maximum exposure: 97 weeks).
Arm Title
Phase 2 Stage 2: Isatuximab + Dexamethasone
Arm Type
Experimental
Arm Description
Participants with relapsed or RRMM, received Isatuximab 20 mg/kg, as IV infusion on Day 1, 8, 15 and Day 22 of Cycle 1 (28 days) and then on Day 1 and 15 of each subsequent 28-day cycles along with dexamethasone: tablet or as IV infusion (40 mg/day for less than [<] 75 years of age; 20 mg/day [greater than or equal to [>=] for 75 years of age) on Days 1, 8, 15 and 22 of each 28 days cycle until unacceptable AE, disease progression, poor compliance to the study protocol, study termination, lost to follow up or investigator's decision (maximum exposure: 97 weeks).
Intervention Type
Drug
Intervention Name(s)
Isatuximab SAR650984
Other Intervention Name(s)
Sarclisa
Intervention Description
Pharmaceutical form: solution for infusion Route of administration: intravenous
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
Pharmaceutical form: solution for infusion Route of administration: intravenous
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
Pharmaceutical form: tablet Route of administration: oral
Primary Outcome Measure Information:
Title
Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs)
Description
DLTs were assessed using the national cancer institute common terminology criteria for adverse events (NCI-CTCAE) version 4.03. DLTs were defined as any Grade 3 or higher non-hematological toxicity (with the exception of allergic reaction/hypersensitivity), Grade 4 neutropenia and/or Grade 4 thrombocytopenia lasting longer than 5 days, attributed to isatuximab. Any other toxicity that the Investigator and the Sponsor deemed to be dose-limiting, regardless of the grade, was also considered as DLT.
Time Frame
Day 1 of Cycle 1 up to Day 14 of Cycle 2
Title
Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Description
Adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily have to have a causal relationship with the treatment. TEAEs were defined as AEs that developed or worsened during the on-treatment period which was defined as the period from the time of first dose of study treatment until 30 days after the last dose of study treatment.
Time Frame
From Baseline up to 30 days after the last dose (maximum duration: 120 weeks )
Title
Phase 2 Stage 1: Percentage of Participants With Overall Response (OR) According to International Myeloma Working Group (IMWG) Uniform Response Criteria
Description
OR defined as participants with stringent complete response (sCR) or complete response (CR) or very good partial response (VGPR) or partial response (PR) . Based on IMWG, CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and <=5% plasma cells in bone marrow; sCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or >=90% reduction in serum M-protein and urine M-protein level <100 mg/24 hours; PR: >=50% reduction of serum M-Protein and reduction in urinary M-protein by >=90% or to <200 mg/24 hours; >=50% decrease in the difference between involved and uninvolved FLC levels in place of the M-protein criteria or a >=50% reduction in plasma cells in place of M-protein if present at baseline.
Time Frame
From the date of randomization until disease progression or death or data cut-off (maximum duration: 77 weeks )
Title
Phase 2 Stage 2: Percentage of Participants With Overall Response According to Updated IMWG Response Criteria
Description
OR: participants with sCR or CR or VGPR or PR. As per updated IMWG, CR: Negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and <=5% plasma cells in bone marrow; normal FLC ratio of 0.26-1.65 in participants with only FLC disease; sCR: CR and normal FLC ratio and no clonal cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or >=90% reduction in serum M-protein and urine M-protein level <100 mg/24 hours, >90% decrease in the difference between involved and uninvolved FLC levels; PR: >=50% reduction of serum M-Protein and reduction in urinary M-protein by >=90% or to <200 mg/24 hours; >=50% decrease in the difference between involved and uninvolved FLC levels in place of M-protein criteria or >=50% reduction in plasma cells in place of M-protein if present at baseline.
Time Frame
From the date of randomization to date of death from any cause (maximum duration: 97 weeks)
Secondary Outcome Measure Information:
Title
Pharmacokinetic (PK) Assessment: Phase 1: Plasma Concentration of Isatuximab Observed at the End of an Intravenous Infusion (Ceoi)
Description
Ceoi was defined as the plasma concentration of Isatuximab at end of infusion. Data for this outcome measure was planned to be collected and analyzed separately for dose 0.3 mg/kg, 1 mg/kg and not for 0.0001, 0.001, 0.01, 0.03 and 0.1 dose levels (reported under one arm, i.e. Phase 1: Isatuximab <=1mg/kg in participant flow). Analysis was performed on PK population: participants who gave informed consent, received at least one dose (even if incomplete) of isatuximab, had an assessable PK parameter.
Time Frame
Cycle 1 Day 1 and Cycle 3 Day 1: At the end of infusion
Title
PK Assessment: Phase 1: Maximum Observed Plasma Concentration (Cmax) of Isatuximab
Description
Data for this outcome measure was planned to be collected and analyzed separately for dose 0.3 mg/kg, 1 mg/kg and not for 0.0001, 0.001, 0.01, 0.03 and 0.1 dose levels (reported under one arm, i.e. Phase 1: Isatuximab <=1mg/kg in participant flow). Analysis was performed on PK population.
Time Frame
For Q2W:Cycle 1,Day 1: pre-dose, 15 min after start of infusion, at the end of infusion, 3, 7, 24, 48 and 168 hr post-infusion; For QW: Cycle 1,Day 1: pre-dose, 15 min after start of infusion, at the end of infusion, 4, 24, 48, 72 and 168 hr post-infusion
Title
PK Assessment: Phase 1: Time to Reach Maximum Plasma Concentration Observed (Tmax) of Isatuximab
Description
Data for this outcome measure was planned to be collected and analyzed separately for dose 0.3 mg/kg, 1 mg/kg and not for 0.0001, 0.001, 0.01, 0.03 and 0.1 dose levels (reported under one arm, i.e. Phase 1: Isatuximab <=1mg/kg in participant flow). Analysis was performed on PK population.
Time Frame
For Q2W:Cycle 1,Day 1: pre-dose, 15 min after start of infusion, at the end of infusion, 3, 7, 24, 48 and 168 hr post-infusion; For QW: Cycle 1,Day 1: pre-dose, 15 min after start of infusion, at the end of infusion, 4, 24, 48, 72 and 168 hr post-infusion
Title
PK Assessment: Phase 1: Plasma Concentration of Isatuximab at Week 1, 2 and 3
Description
Data for this outcome measure was planned to be collected and analyzed only for dose 1 mg/kg and not for 0.0001, 0.001, 0.01, 0.03, 0.1 and 0.3 mg/kg dose levels (reported under one arm, i.e. Phase 1: Isatuximab <=1mg/kg in participant flow).
Time Frame
Week 1, 2 and 3
Title
PK Assessment: Phase 1: Predicted Cumulative Area Under the Plasma Concentration Curve (AUC) of Isatuximab Over the First Week (0-168 Hours) (AUC1W)
Description
Data for this outcome measure was planned to be collected and analyzed only for dose 1 mg/kg and not for 0.0001, 0.001, 0.01, 0.03, 0.1 and 0.3 mg/kg dose levels (reported under one arm, i.e. Phase 1: Isatuximab <=1mg/kg in participant flow).
Time Frame
For Q2W:Cycle 1,Day 1: pre-dose, 15 min after start of infusion, at the end of infusion, 3, 7, 24, 48 and 168 hr post-infusion; For QW: Cycle 1,Day 1: pre-dose, 15 min after start of infusion, at the end of infusion, 4, 24, 48, 72 and 168 hr post-infusion
Title
PK Assessment: Phase 1: Predicted Cumulative Area Under the Plasma Concentration Curve (AUC) of Isatuximab Over the First 2 Weeks (0-336 Hours) (AUC2W)
Description
Data for this outcome measure was planned to be collected and analyzed only for dose 1 mg/kg and not for 0.0001, 0.001, 0.01, 0.03, 0.1 and 0.3 mg/kg dose levels (reported under one arm, i.e. Phase 1: Isatuximab <=1mg/kg in participant flow).
Time Frame
For Q2W:Cycle 1,Day 1: pre-dose, 15 min after start of infusion, at the end of infusion, 3, 7, 24, 48 and 336 hr post-infusion; For QW: Cycle 1,Day 1: pre-dose, 15 min after start of infusion, at the end of infusion, 4, 24, 48, 72 and 336 hr post-infusion
Title
Pharmacodynamic (PD) Assessment: Phase 1: Change From Baseline in Serum/Plasma Markers
Description
Serum/plasma markers included: tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1-β), interleukin 6 (IL-6) and interferon-gamma (IFN-Gamma). Due to change in planned analysis, data for high-sensitivity C-reactive protein (hs-CRP) and CD38 was not collected and analyzed.
Time Frame
Cycle 1 Day 1
Title
Immunogenicity Assessment: Phase 1: Number of Participants With Treatment-Emergent And Treatment-Boosted Anti-drug Antibodies (ADA) Response
Description
ADA response was categorized as: treatment induced and treatment boosted response. Treatment-induced ADA was defined as ADA that developed at any time during the ADA on-study observation period (defined as the time from the first isatuximab administration until end of Phase 1) in participants without preexisting ADA (defined as: ADA that were present in samples drawn before treatment), including participants without pre-treatment (before treatment) samples. Treatment boosted ADA was defined as pre-existing ADA that increased at least 2 titer steps between pre-treatment (before treatment) and post-treatment.
Time Frame
Up to 120 weeks
Title
Clinical Assessment: Phase 1: Percentage of Participants With Overall Response and Clinical Benefit: Assessed Using European Society for Blood and Marrow Transplantation (EBMT) Criteria
Description
OR defined as participants with complete response (CR) or partial response (PR) as best overall response (BOR). Clinical benefit: participants with minimal response (MR) or better as BOR. BOR: best sequential response from start of treatment through the entire study excluding any time point following start of other treatment. CR: negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas, <5% plasma cells in bone marrow aspirates, no increase in size or number of lytic bone lesions. PR: >=50% reduction of serum M-protein, reduction in 24 h urinary M-protein by >=90% or <200mg, >=50% reduction in size/number of soft tissue plasmacytomas, no increase in size or number of lytic bone lesions. MR: 25 to 49% reduction in serum M-protein, 50-89% reduction in 24h urine M-protein, 25-49% reduction in size of soft tissue plasmacytomas, no increase in size or number of lytic bone lesions.
Time Frame
From the date of randomization to the date of first documentation of progression or death (due to any cause) (maximum duration: 120 weeks)
Title
Clinical Assessment: Phase 1: Duration of Response (DOR)
Description
DOR: time from first response (PR or better) to first documented tumor progression/death. Progression as per EBMT: >25% increase in serum monoclonal paraprotein level, which must also be an absolute increase of >= 5 g/l: confirmed by >=1 repeated investigation; >25% increase in 24h urinary light chain excretion, which must also be an absolute increase of >=200 mg/24 h:confirmed by >=1 repeated investigation; >25% increase in plasma cells in a bone marrow aspirate/on trephine biopsy, which must also be an absolute increase of >= 10%; definite increase in size of existing bone lesions/soft tissue plasmacytomas; development of new bone lesions/soft tissue plasmacytomas; development of hypercalcemia (corrected serum calcium >11·5 mg/dl or 2·8 mmol/l) not attributable to any other cause. PR: >=50% reduction of serum M-protein, reduction in 24h urinary M-protein by >=90% or <200mg, >=50% reduction in size/number of soft tissue plasmacytomas, no increase in size/number of lytic bone lesions.
Time Frame
From the date of first response to the date of first documentation of progression or death (due to any cause) (maximum duration: 120 weeks)
Title
Clinical Assessment: Phase 1: Time to First Response (TTR)
Description
TTR was defined as the time from first dose of isatuximab to first response (PR or better). PR: >=50% reduction of serum M-protein, reduction in 24 h urinary M-protein by >=90% or <200mg, >=50% reduction in size/number of soft tissue plasmacytomas, no increase in size or number of lytic bone lesions.
Time Frame
From the date of first dose administration to the date of first response or death (due to any cause) (maximum duration: 120 weeks)
Title
Clinical Assessment: Phase 1: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) (Karnofsky Performance Status)-Shift From Baseline Value to Best Value During Treatment
Description
ECOG performance status was measured on a 4 point scale to assess participant's performance status. 0=Normal, fully functional; 1=Fatigue without significant decrease in daily activity; 2=Fatigue with significant impairment of daily activities or bed rest <50% of waking hours; 3=Bed rest/sitting >50% of waking hours; 4=Bedridden or unable to care for self, where lower score indicated good performance status. Number of participants with Baseline ECOG PS score and corresponding changes to the best values (categorized as: Baseline ECOG 1, During Treatment ECOG 0; Baseline ECOG 2, During Treatment ECOG 0; Baseline ECOG 2, During Treatment ECOG 1) are reported.
Time Frame
At baseline, during treatment (Day 1 up to 120 weeks)
Title
Clinical Assessment: Phase 1: Number of Participants With Eastern Cooperative Oncology Group Performance Status (Karnofsky Performance Status)-Shift From Baseline Value to Worst Value During Treatment
Description
ECOG performance status was measured on a 4 point scale to assess participant's performance status. 0=Normal, fully functional; 1=Fatigue without significant decrease in daily activity; 2=Fatigue with significant impairment of daily activities or bed rest <50% of waking hours; 3=Bed rest/sitting>50% of waking hours; 4=Bedridden or unable to care for self, where higher score indicated worst performance status. Number of participants with Baseline ECOG PS score and corresponding changes to the worst values (categorized as: Baseline ECOG 0, During Treatment ECOG 1; Baseline ECOG 2, During Treatment ECOG 1; Baseline ECOG 0, During Treatment ECOG 2; Baseline ECOG 1, During Treatment ECOG 2; Baseline ECOG 0, During Treatment ECOG 3; Baseline ECOG 1, During Treatment ECOG 3; Baseline ECOG 2, During Treatment ECOG 3) are reported.
Time Frame
At baseline, during treatment (up to 120 weeks)
Title
Phase 2 Stage 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Description
Adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily have to have a causal relationship with the treatment. TEAEs were defined as AEs that developed or worsened during the on-treatment period which was defined as the period from the time of first dose of study treatment until 30 days after the last dose of study treatment.
Time Frame
From Baseline up to 30 days after the last dose (maximum duration: 77 weeks for Stage 1a arms and 53 weeks for stage 1b arm)
Title
Phase 2 Stage 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Description
AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily have to have a causal relationship with the treatment. TEAEs were defined as AEs that developed or worsened during the on-treatment period which was defined as the period from the time of first dose of study treatment until 30 days after the last dose of study treatment.
Time Frame
From Baseline up to 30 days after the last dose (maximum duration: 97 weeks)
Title
Phase 2 Stage 1: Duration of Response
Description
DOR:Time from date of 1st IAC determined response (>= PR) that was subsequently confirmed, to date of first IAC determined PD/death, whichever happened earlier. updated IMWG criteria- PR:>=50% decrease in difference between involved and uninvolved FLC levels in place of M-protein criteria or a >=50% reduction in plasma cells in place of M-protein if baseline was ≥30%. If present at baseline a >=50% reduction in size of soft tissue plasmacytomas; PD: Increase of 25% from lowest response value in any of following: Serum M-protein >=0.5 g/dL absolute increase and/or urine M-protein >=200 mg/24 hours absolute increase and/or >10 mg/dL absolute increase in difference between involved and uninvolved FLC levels, >=10% bone marrow plasma cells (PCs), development of new bone lesions/soft tissue plasmacytomas or definite increase in size of existing bone lesions/soft tissue plasmacytomas, development of hypercalcemia (corrected serum calcium >11·5 mg/dl) attributed to PC proliferation disorder.
Time Frame
From the date of first response until disease progression or death or data cut-off (maximum duration: 77 weeks for Stage 1a arms and 53 weeks for stage 1b arm)
Title
Phase 2 Stage 2: Duration of Response
Description
DOR: Time from date of 1st IAC determined response (>= PR) that was subsequently confirmed, to date of 1st IAC determined PD or death, whichever happened earlier. As per updated IMWG criteria-PR: ≥50% reduction of serum M-Protein and reduction in urinary M-protein by ≥90% or to <200 mg/24 hours. ≥50% decrease in difference between involved and uninvolved FLC levels in place of M-protein criteria or ≥50% reduction in plasma cells in place of M-protein if baseline was ≥30%. If present at baseline ≥50% reduction in size of soft tissue plasmacytomas; PD: Increase of >25% from lowest response value in any one of following: Serum M-component (absolute increase must be >0.5 g/dL)4 and/or Urine M-component (absolute increase must be >200 mg/24 h) and/or >10 mg/dL absolute increase in difference between involved and uninvolved FLC levels, >=10% bone marrow plasma cell, development of hypercalcemia (corrected serum calcium >11.5 mg/dL) attributed solely to plasma cell proliferative disorder.
Time Frame
From the date of first response until disease progression or death or data cut-off (maximum duration: 97 weeks)
Title
Phase 2 Stage 1: Percentage of Participants With Clinical Benefit
Description
Clinical benefit: participants with sCR, CR, VGPR, PR or MR as per IMWG criteria, determined by IAC. CR: negative immunofixation on serum & urine, disappearance of any soft tissue plasmacytomas,<5% PCs in bone marrow aspirates. sCR: CR + normal FLC ratio (0.26-1.65), absence of clonal cells in bone marrow biopsy. VGPR: serum & urine M-component detectable by immunofixation, not on electrophoresis/,>=90% reduction in serum M-component plus urine M-component level <100mg/24hours; PR: ≥50% reduction of serum M-Protein and reduction in urinary M-protein by ≥90% or to <200 mg/24 hours, ≥50% decrease in the difference between involved and uninvolved FLC levels in place of the M-protein criteria or a ≥50% reduction in plasma cells in place of M-protein if baseline was ≥30%. If present at baseline, ≥50% size reduction in soft tissue plasmacytomas. MR:>=25 but <49% reduction in serum M-protein, reduction in 24h urine M-protein by 50-89%, 25-49% size reduction in soft tissue plasmacytomas.
Time Frame
From Baseline up to 30 days after the last dose (maximum duration: 77 weeks for Stage 1a arms and 53 weeks for stage 1b arm)
Title
Phase 2 Stage 2: Percentage of Participants With Clinical Benefit
Description
Clinical benefit:participants with sCR, CR, VGPR, PR or MR, per IMWG criteria, determined by IAC. CR:negative immunofixation on serum & urine, disappearance of any soft tissue plasmacytomas,<5% plasma cells in bone marrow aspirates,normal FLC ratio(0.26-1.65) in participants with only FLC disease.sCR:CR+normal FLC ratio, absence of clonal cells in bone marrow biopsy.VGPR:serum & urine M-component detectable by immunofixation, not on electrophoresis/,>=90% reduction in serum M-component plus urine M-component level <100mg/24h/,>=90% decrease in difference between involved and uninvolved FLC levels; PR:>=50% reduction of serum M-protein, reduction in 24h urinary M-protein by >=90%/<200mg/24h,>50% decrease in difference between involved and uninvolved FLC in place of M-protein criteria, >=50% reduction in size/number of soft tissue plasmacytomas. MR:>=25 but <49% reduction in serum M-protein,reduction in 24h urine M-protein by 50-89%, 25-49% reduction in size of soft tissue plasmacytomas
Time Frame
From the date of randomization to the date of first documentation of progression or death (maximum duration: 97 weeks )
Title
Phase 2 Stage 1: Progression Free Survival (PFS)
Description
PFS was defined as the time interval from the date of first isatuximab administration to the date of the first IAC-confirmed disease progression (PD) or date of death due to any cause, whichever came first. As per IMWG criteria, PD: Increase of > 25% from lowest response value in any one or more of the following: Serum M-component and/or (the absolute increase must be > 0.5 g/dL), Urine M-component and/or (the absolute increase must be > 200 mg/24 h), > 10mg/dL decrease in the difference between involved and uninvolved FLC levels in place of the M-protein criteria, >10% absolute percentage of bone marrow plasma cell, definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas, development of hypercalcemia (corrected serum calcium > 11.5 mg/dL or 2.65 mmol/L) that attributed solely to the plasma cell proliferative disorder. Analysis was performed by Kaplan-Meier method.
Time Frame
From the date of the first dose administration until progression or death, whichever occurred first (maximum duration: 77 weeks for Stage 1a arms and 53 weeks for stage 1b arm)
Title
Phase 2 Stage 2: Progression Free Survival
Description
PFS was defined as the time interval from the date of first isatuximab administration to the date of the first IAC-confirmed disease progression or the date of death due to any cause, whichever came first. As per IMWG criteria, PD: Increase of >25% from lowest response value in any one of the following: Serum M-component (the absolute increase must be >0.5 g/dL)4 and/or Urine M-component (the absolute increase must be >200 mg/24 h) and/or >10 mg/dL decrease in the difference between involved and uninvolved FLC levels in place of the M-protein criteria, ≥10% bone marrow plasma cell, development of hypercalcemia (corrected serum calcium >11.5 mg/dL) attributed solely to the plasma cell proliferative disorder. Analysis was performed by Kaplan-Meier method.
Time Frame
From the date of the first dose administration until progression or death, whichever occurred first (maximum duration: 97 weeks)
Title
Phase 2 Stage 1: Overall Survival (OS)
Description
OS was defined as the time interval from the date of first Isatuximab administration to death from any cause. Analysis was performed by Kaplan-Meier method.
Time Frame
From the date of randomization to date of death from any cause (maximum duration 77 weeks for Stage 1a arms and 53 weeks for stage 1b arm)
Title
Phase 2 Stage 2: Overall Survival
Description
OS was defined as the time interval from the date of first Isatuximab administration to death from any cause. Analysis was performed by Kaplan-Meier method.
Time Frame
From the date of randomization to date of death from any cause (maximum duration: 97 weeks)
Title
Phase 2 Stage 1: Change From Baseline in Health Related Quality of Life (HRQL) European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scores: Global Health Status
Description
EORTC-QLQ-C30 is a cancer-specific instrument with 30 questions for evaluation of new chemotherapy and provides an assessment of participant reported outcome dimensions. First 28 questions used 4-point scale (1=not at all,2=a little,3=quite a bit,4=very much) for evaluating 5 functional scales (physical, role, emotional, cognitive, social), 3 symptom scales (fatigue, nausea/vomiting, pain) & other single items. For each item, high score = high level of symptomatology/problem. Last 2 questions represented participant's assessment of overall health & quality of life, coded on 7-point scale (1=very poor to 7=excellent). EORTC QLQ-C30 observed values and change from baseline for global health status (scoring of questions 29 & 30) and 5 functional scales, 3 symptom scales and other single items (scoring of questions 1 to 28). Answers were converted into grading scale, with values between 0 and 100. A high score represented a favorable outcome with a best quality of life for participant.
Time Frame
Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10 and End of Treatment (EOT: anytime up to 77 weeks for Stage 1a arms and 53 weeks for stage 1b arm)
Title
Phase 2 Stage 1: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20) Scores: Disease Symptom Subscale Score
Description
EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in participants with MM. It has 4 subscales: body image, future perspective), and 2 symptoms scales (disease symptoms and side-effects of treatment). Disease symptoms subscale used 4-point scale ranged from 1= 'Not at All' to 4= 'Very Much'. Scores were averaged, and transformed to 0 -100 scale, where higher scores = more symptoms and lower health-related quality of life (HRQL) and lower score = less symptoms and more HRQL.
Time Frame
Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10 and EOT (anytime up to 77 weeks for Stage 1a arms and 53 weeks for stage 1b arm)
Title
Phase 2 Stage 1: Change From Baseline in Euro Quality of Life 5 Dimension (EQ-5D) Generic Health Status - Visual Analogue Scale Scores
Description
EQ-5D was a standardized HRQL questionnaire consisting of EQ-5D descriptive system and Visual Analogue Scale (VAS). EQ-5D VAS was used to record a participant's rating for his/her current health-related quality of life state and captured on a vertical VAS (0-100), where 0 = worst imaginable health state and 100 = best imaginable health state.
Time Frame
Baseline, Day 1 of Cycles 4, 7, 10, 13, 16, 19, and EOT (anytime up to 77 weeks for Stage 1a arms and 53 weeks for stage 1b arm)
Title
Pharmacokinetic Assessment: Phase 2 Stage 2: Area Under the Plasma Concentration Versus Time Curve of Isatuximab Over 1 Week Interval
Time Frame
Pre-dose, at the end of infusion, 1 hour and 168 hours post dose on Day 1 of Cycle 1
Title
Pharmacokinetic Assessment: Phase 2 Stage 2: Area Under the Plasma Concentration Versus Time Curve of Isatuximab Over 2 Weeks Interval
Time Frame
Cycle 1, Day 1: pre-dose, at the end of infusion, 168 and 336 hours post-infusion
Title
Pharmacokinetic Assessment: Phase 2 Stage 2: Area Under the Plasma Concentration Versus Time Curve of Isatuximab Over 4 Weeks Interval
Time Frame
Cycle 1, Day 1: pre-dose, at the end of infusion, 168, 336, and 672 hours post-infusion
Title
Pharmacokinetic Assessment: Phase 2 Stage 2: Plasma Concentration of Isatuximab Before Treatment Administration (Ctrough)
Time Frame
At Day 1, 8, and 22
Title
Pharmacokinetic Assessment: Phase 2 Stage 2: Accumulation Ratio of Isatuximab Based on Ctrough
Description
Ctrough is the plasma concentration observed before treatment administration. For 1st category, the accumulation ratio was calculated by dividing Ctrough value of Cycle 2 Day 1 by Cycle 1 Day 8 and for second category, accumulation ratio was calculated by dividing Ctrough value of Cycle 4 Day 1 by Cycle 1 Day 8.
Time Frame
Cycle 2, Day 1; Cycle 1, Day 8; Cycle 4, Day 1
Title
Immunogenicity Assessment: Phase 2 Stage 2: Number of Participants With Anti-drug Antibodies to Isatuximab
Description
ADA response was categorized as: treatment induced and treatment boosted response. Treatment-induced ADA was defined as ADA that developed at any time during the ADA on-study observation period (defined as the time from the first isatuximab administration until end of Phase 2 Stage 2) in participants without preexisting ADA (defined as: ADA that were present in samples drawn before treatment), including participants without pre-treatment (before treatment) samples. Treatment boosted ADA was defined as pre-existing ADA that increased at least 2 titer steps between pre-treatment (before treatment) and post-treatment.
Time Frame
Up to 97 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site Number 840003
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85054
Country
United States
Facility Name
Investigational Site Number 840005
City
San Francisco
State/Province
California
ZIP/Postal Code
94117
Country
United States
Facility Name
Investigational Site Number 840009
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Investigational Site Number 840010
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Investigational Site Number 840022
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109-0759
Country
United States
Facility Name
Investigational Site Number 840027
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Investigational Site Number 840018
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Investigational Site Number 840013
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Investigational Site Number 840011
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Investigational Site Number 840014
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Investigational Site Number 840016
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27707
Country
United States
Facility Name
Investigational Site Number 840004
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267-0542
Country
United States
Facility Name
Investigational Site Number 840001
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Investigational Site Number 840002
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112-5550
Country
United States
Facility Name
Investigational Site Number 840012
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
Investigational Site Number 840017
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Investigational Site Number 032002
City
Caba
ZIP/Postal Code
C1181ACH
Country
Argentina
Facility Name
Investigational Site Number 032003
City
Capital Federal
ZIP/Postal Code
C1425ASS
Country
Argentina
Facility Name
Investigational Site Number 032001
City
Ciudad De Buenos Aires
ZIP/Postal Code
C1426ANZ
Country
Argentina
Facility Name
Investigational Site Number 056001
City
Antwerpen
ZIP/Postal Code
2060
Country
Belgium
Facility Name
Investigational Site Number 076001
City
Barretos
ZIP/Postal Code
14784-400
Country
Brazil
Facility Name
Investigational Site Number 076003
City
Porto Alegre
ZIP/Postal Code
90470-340
Country
Brazil
Facility Name
Investigational Site Number 076004
City
Rio De Janeiro
ZIP/Postal Code
22793-080
Country
Brazil
Facility Name
Investigational Site Number 076002
City
Sao Paulo
ZIP/Postal Code
04537-081
Country
Brazil
Facility Name
Investigational Site Number 152001
City
Temuco
ZIP/Postal Code
4810469
Country
Chile
Facility Name
Investigational Site Number 246001
City
Helsinki
ZIP/Postal Code
00029
Country
Finland
Facility Name
Investigational Site Number 246002
City
Turku
ZIP/Postal Code
20521
Country
Finland
Facility Name
Investigational Site Number 250003
City
Nantes Cedex 01
ZIP/Postal Code
44093
Country
France
Facility Name
Investigational Site Number 250004
City
Pierre Benite
ZIP/Postal Code
69310
Country
France
Facility Name
Investigational Site Number 250001
City
Toulouse Cedex 9
ZIP/Postal Code
31059
Country
France
Facility Name
Investigational Site Number 300001
City
Athens
ZIP/Postal Code
11528
Country
Greece
Facility Name
Investigational Site Number 376004
City
Jerusalem
ZIP/Postal Code
91120
Country
Israel
Facility Name
Investigational Site Number 376002
City
Tel Hashomer
ZIP/Postal Code
52621
Country
Israel
Facility Name
Investigational Site Number 380001
City
Bologna
ZIP/Postal Code
40138
Country
Italy
Facility Name
Investigational Site Number 380002
City
Torino
ZIP/Postal Code
10126
Country
Italy
Facility Name
Investigational Site Number 484001
City
Monterrey
ZIP/Postal Code
64460
Country
Mexico
Facility Name
Investigational Site Number 484003
City
San Luis Potosi
ZIP/Postal Code
78419
Country
Mexico
Facility Name
Investigational Site Number 604001
City
Arequipa
Country
Peru
Facility Name
Investigational Site Number 604002
City
Lima
ZIP/Postal Code
LIMA 34
Country
Peru
Facility Name
Investigational Site Number 643002
City
Moscow
ZIP/Postal Code
125284
Country
Russian Federation
Facility Name
Investigational Site Number 643003
City
Novosibirsk
ZIP/Postal Code
630087
Country
Russian Federation
Facility Name
Investigational Site Number 643001
City
Petrozavodsk
ZIP/Postal Code
185019
Country
Russian Federation
Facility Name
Investigational Site Number 643004
City
Saint-Petersburg
ZIP/Postal Code
194291
Country
Russian Federation
Facility Name
Investigational Site Number 724007
City
Badalona
ZIP/Postal Code
08916
Country
Spain
Facility Name
Investigational Site Number 724005
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Investigational Site Number 724004
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Investigational Site Number 724002
City
Pamplona
ZIP/Postal Code
31008
Country
Spain
Facility Name
Investigational Site Number 724001
City
Salamanca
ZIP/Postal Code
37007
Country
Spain
Facility Name
Investigational Site Number 724008
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Facility Name
Investigational Site Number 724006
City
Valencia
ZIP/Postal Code
46017
Country
Spain
Facility Name
Investigational Site Number 792002
City
Ankara
ZIP/Postal Code
06200
Country
Turkey
Facility Name
Investigational Site Number 792005
City
Ankara
ZIP/Postal Code
06500
Country
Turkey
Facility Name
Investigational Site Number 792001
City
İstanbul
Country
Turkey
Facility Name
Investigational Site Number 792004
City
Samsun
ZIP/Postal Code
55139
Country
Turkey
Facility Name
Investigational Site Number 804001
City
Kyiv
ZIP/Postal Code
04112
Country
Ukraine
Facility Name
Investigational Site Number 804004
City
Vinnitsya
ZIP/Postal Code
21018
Country
Ukraine
Facility Name
Investigational Site Number 804002
City
Zaporizhzhya
ZIP/Postal Code
69600
Country
Ukraine
Facility Name
Investigational Site Number 826001
City
Nottingham
ZIP/Postal Code
NG5 1PB
Country
United Kingdom
Facility Name
Investigational Site Number 826002
City
Southampton
ZIP/Postal Code
SO16 6YD
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Citations:
PubMed Identifier
33080623
Citation
Dimopoulos M, Bringhen S, Anttila P, Capra M, Cavo M, Cole C, Gasparetto C, Hungria V, Jenner M, Vorobyev V, Ruiz EY, Yin JY, Saleem R, Hellet M, Mace S, Paiva B, Vij R. Isatuximab as monotherapy and combined with dexamethasone in patients with relapsed/refractory multiple myeloma. Blood. 2021 Mar 4;137(9):1154-1165. doi: 10.1182/blood.2020008209.
Results Reference
derived
PubMed Identifier
32409691
Citation
Mikhael J, Richter J, Vij R, Cole C, Zonder J, Kaufman JL, Bensinger W, Dimopoulos M, Lendvai N, Hari P, Ocio EM, Gasparetto C, Kumar S, Oprea C, Chiron M, Brillac C, Charpentier E, San-Miguel J, Martin T. A dose-finding Phase 2 study of single agent isatuximab (anti-CD38 mAb) in relapsed/refractory multiple myeloma. Leukemia. 2020 Dec;34(12):3298-3309. doi: 10.1038/s41375-020-0857-2. Epub 2020 May 14.
Results Reference
derived

Learn more about this trial

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

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