Trial Outcomes & Findings for Isatuximab in Combination With Chemotherapy in Pediatric Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia or Acute Myeloid Leukemia (NCT NCT03860844)

Last Updated: 2025-09-09

Results Overview

The complete response rate (CR + CRi \[complete response with incomplete peripheral recovery\]) was defined as the percentage of participants achieving complete response (CR + CRi) assessed by the investigator per National Comprehensive Cancer Network (NCCN) guidelines version 1.2018 criteria. CR was defined as \<5% blasts in a bone marrow aspirate (BMA) with spicules; no circulating blasts (ALL)/no blasts with Auer rods (AML) or extramedullary disease, no lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/central nervous system involvement (ALL), trilineage hematopoiesis (ALL); Absolute neutrophil count (ANC) \>=1000/microliter (mcL); platelets \>100000/mcL; red blood cell transfusion independence. If the physician documented transfusion dependency related to study treatment and not to the participant's underlying disease, CRi was reported. CRi met the same criteria as for CR, except neutrophils and/or platelets recovery (ANC \<1000/mcL or platelets \<100000/mcL).

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

67 participants

Primary outcome timeframe

From enrollment until the primary analysis completion date of 12 Sep 2022; the median duration of exposure was approximately 7 weeks

Results posted on

2025-09-09

Participant Flow

This Phase II, open-label, single-arm study was conducted in 3 separate cohorts at 41 investigational sites in 16 countries. A total of 67 participants were enrolled between 06 Aug 2019 and 08 Jun 2022.

The study consisted of a screening period (up to 3 weeks prior to the first study treatment administration), treatment period \[Day 1 to Day 57 for Acute Lymphoblastic Leukemia(ALL); Day 1 to Day 22 for Acute Myeloid Leukemia(AML)\],a period of aplasia followed by recovery period;an end of treatment (EOT) visit within 30 days after hematological recovery and a follow-up period.The study was prematurely stopped due to sponsor decision (stage 2 efficacy criteria not met);not due to safety concerns.

Participant milestones

Participant milestones
Measure	B-cell Acute Lymphoblastic Leukemia (B-ALL) Participants with B-ALL received isatuximab 20 milligram per kilogram (mg/kg) intravenous (IV) infusion once every week (QW) for 4 weeks during the induction period (i.e., on Days 1, 8, 15, and 22) and every 2 weeks (Q2W) during the consolidation period (i.e., on Days 29, 43, and 57. Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.	T-cell Acute Lymphoblastic Leukemia (T-ALL) Participants with T-ALL received isatuximab 20 mg/kg IV infusion QW for 4 weeks during the induction period (i.e., on Days 1, 8, 15, and 22) and Q2W during the consolidation period (i.e., on Days 29, 43, and 57. Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.	Acute Myeloid Leukemia (AML) Participants with AML received isatuximab 20 mg/kg IV infusion on Days 1, 8, and 15 of each Cycle (up to 2 treatment cycles, each cycle 28 days). Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.
Overall Study STARTED	27	13	27
Overall Study COMPLETED	19	7	20
Overall Study NOT COMPLETED	8	6	7

Reasons for withdrawal

Reasons for withdrawal
Measure	B-cell Acute Lymphoblastic Leukemia (B-ALL) Participants with B-ALL received isatuximab 20 milligram per kilogram (mg/kg) intravenous (IV) infusion once every week (QW) for 4 weeks during the induction period (i.e., on Days 1, 8, 15, and 22) and every 2 weeks (Q2W) during the consolidation period (i.e., on Days 29, 43, and 57. Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.	T-cell Acute Lymphoblastic Leukemia (T-ALL) Participants with T-ALL received isatuximab 20 mg/kg IV infusion QW for 4 weeks during the induction period (i.e., on Days 1, 8, 15, and 22) and Q2W during the consolidation period (i.e., on Days 29, 43, and 57. Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.	Acute Myeloid Leukemia (AML) Participants with AML received isatuximab 20 mg/kg IV infusion on Days 1, 8, and 15 of each Cycle (up to 2 treatment cycles, each cycle 28 days). Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.
Overall Study Adverse event, not related to Coronavirus Disease-2019 (COVID-19)	3	2	3
Overall Study Progressive disease	5	3	4
Overall Study Other, Not related to COVID-19	0	1	0

Baseline Characteristics

Isatuximab in Combination With Chemotherapy in Pediatric Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia or Acute Myeloid Leukemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	B-cell Acute Lymphoblastic Leukemia (B-ALL) n=27 Participants Participants with B-ALL received isatuximab 20 mg/kg IV infusion QW for 4 weeks during the induction period (i.e., on Days 1, 8, 15, and 22) and Q2W during the consolidation period (i.e., on Days 29, 43, and 57. Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.	T-cell Acute Lymphoblastic Leukemia (T-ALL) n=13 Participants Participants with T-ALL received isatuximab 20 mg/kg IV infusion QW for 4 weeks during the induction period (i.e., on Days 1, 8, 15, and 22) and Q2W during the consolidation period (i.e., on Days 29, 43, and 57. Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.	Acute Myeloid Leukemia (AML) n=27 Participants Participants with AML received isatuximab 20 mg/kg IV infusion on Days 1, 8, and 15 of each Cycle (up to 2 treatment cycles, each cycle 28 days). Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.	Total n=67 Participants Total of all reporting groups
Age, Continuous	8.22 years STANDARD_DEVIATION 3.92 • n=39 Participants	8.72 years STANDARD_DEVIATION 4.15 • n=41 Participants	9.04 years STANDARD_DEVIATION 5.41 • n=35 Participants	8.65 years STANDARD_DEVIATION 4.56 • n=31 Participants
Sex: Female, Male Female	10 Participants n=39 Participants	4 Participants n=41 Participants	12 Participants n=35 Participants	26 Participants n=31 Participants
Sex: Female, Male Male	17 Participants n=39 Participants	9 Participants n=41 Participants	15 Participants n=35 Participants	41 Participants n=31 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants	3 Participants n=31 Participants
Race (NIH/OMB) Asian	1 Participants n=39 Participants	1 Participants n=41 Participants	4 Participants n=35 Participants	6 Participants n=31 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants	0 Participants n=31 Participants
Race (NIH/OMB) Black or African American	1 Participants n=39 Participants	1 Participants n=41 Participants	2 Participants n=35 Participants	4 Participants n=31 Participants
Race (NIH/OMB) White	17 Participants n=39 Participants	7 Participants n=41 Participants	15 Participants n=35 Participants	39 Participants n=31 Participants
Race (NIH/OMB) More than one race	1 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants	1 Participants n=31 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=39 Participants	4 Participants n=41 Participants	6 Participants n=35 Participants	14 Participants n=31 Participants

PRIMARY outcome

Timeframe: From enrollment until the primary analysis completion date of 12 Sep 2022; the median duration of exposure was approximately 7 weeks

Population: The evaluable population consisted of evaluable participants from the AT population who received at least 1 full dose of isatuximab in Cycle 1 and who had at least 1 valid response value that was evaluable.

Outcome measures

Outcome measures
Measure	B-cell Acute Lymphoblastic Leukemia (B-ALL) n=25 Participants Participants with B-ALL received isatuximab 20 mg/kg IV infusion QW for 4 weeks during the induction period (i.e., on Days 1, 8, 15, and 22) and Q2W during the consolidation period (i.e., on Days 29, 43, and 57. Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.	T-cell Acute Lymphoblastic Leukemia (T-ALL) n=11 Participants Participants with T-ALL received isatuximab 20 mg/kg IV infusion QW for 4 weeks during the induction period (i.e., on Days 1, 8, 15, and 22) and Q2W during the consolidation period (i.e., on Days 29, 43, and 57. Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.	Acute Myeloid Leukemia (AML) n=23 Participants Participants with AML received isatuximab 20 mg/kg IV infusion on Days 1, 8, and 15 of each Cycle (up to 2 treatment cycles, each cycle 28 days). Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.
Percentage of Participants With Complete Response (CR) Rate	52.0 percentage of participants	45.5 percentage of participants	60.9 percentage of participants

SECONDARY outcome

Timeframe: From the time of the first treatment administration (Day 1) up to 30 days after the last treatment (maximum duration of exposure of 13.1 weeks for B-ALL cohort, 10.7 weeks for T-ALL cohort and 7.1 weeks for AML cohort)

Population: The AT population consisted of all participants who received at least 1 dose (even incomplete) of study treatment.

An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of study treatment, whether or not considered related to the study treatment. SAEs were any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were defined as an AE which occurred after the first dose of study treatment administration until the last dose plus 30 days, or until the start of hematological recovery period or a new anti-leukemia/lymphoma therapy, whichever occurred first.

Outcome measures

Outcome measures
Measure	B-cell Acute Lymphoblastic Leukemia (B-ALL) n=27 Participants Participants with B-ALL received isatuximab 20 mg/kg IV infusion QW for 4 weeks during the induction period (i.e., on Days 1, 8, 15, and 22) and Q2W during the consolidation period (i.e., on Days 29, 43, and 57. Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.	T-cell Acute Lymphoblastic Leukemia (T-ALL) n=13 Participants Participants with T-ALL received isatuximab 20 mg/kg IV infusion QW for 4 weeks during the induction period (i.e., on Days 1, 8, 15, and 22) and Q2W during the consolidation period (i.e., on Days 29, 43, and 57. Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.	Acute Myeloid Leukemia (AML) n=27 Participants Participants with AML received isatuximab 20 mg/kg IV infusion on Days 1, 8, and 15 of each Cycle (up to 2 treatment cycles, each cycle 28 days). Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) Any TEAE	27 Participants	13 Participants	26 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) Any TESAE	19 Participants	12 Participants	17 Participants

SECONDARY outcome

Population: The AT population consisted of all participants who received at least 1 dose (even incomplete) of study treatment.

An IR was an AE related to isatuximab typically with onset within 24 hours from the start of the isatuximab infusion and was reported by the investigator.

Outcome measures

Outcome measures
Measure	B-cell Acute Lymphoblastic Leukemia (B-ALL) n=27 Participants Participants with B-ALL received isatuximab 20 mg/kg IV infusion QW for 4 weeks during the induction period (i.e., on Days 1, 8, 15, and 22) and Q2W during the consolidation period (i.e., on Days 29, 43, and 57. Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.	T-cell Acute Lymphoblastic Leukemia (T-ALL) n=13 Participants Participants with T-ALL received isatuximab 20 mg/kg IV infusion QW for 4 weeks during the induction period (i.e., on Days 1, 8, 15, and 22) and Q2W during the consolidation period (i.e., on Days 29, 43, and 57. Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.	Acute Myeloid Leukemia (AML) n=27 Participants Participants with AML received isatuximab 20 mg/kg IV infusion on Days 1, 8, and 15 of each Cycle (up to 2 treatment cycles, each cycle 28 days). Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.
Number of Participants With Infusion Reactions (IRs)	9 Participants	5 Participants	15 Participants

SECONDARY outcome

Timeframe: From Week 0 to Week 1, Week 0 to Week 5, and Week 0 to Week 10

Population: The Pharmacokinetic (PK) population consisted of all participants from the AT population with at least 1 PK parameter available (isatuximab concentration). Only those participants with data available at specified timepoints were analyzed.

Plasma samples were collected at specified timepoints to determine the AUC of isatuximab.

Outcome measures

Outcome measures
Measure	B-cell Acute Lymphoblastic Leukemia (B-ALL) n=27 Participants Participants with B-ALL received isatuximab 20 mg/kg IV infusion QW for 4 weeks during the induction period (i.e., on Days 1, 8, 15, and 22) and Q2W during the consolidation period (i.e., on Days 29, 43, and 57. Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.	T-cell Acute Lymphoblastic Leukemia (T-ALL) n=12 Participants Participants with T-ALL received isatuximab 20 mg/kg IV infusion QW for 4 weeks during the induction period (i.e., on Days 1, 8, 15, and 22) and Q2W during the consolidation period (i.e., on Days 29, 43, and 57. Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.	Acute Myeloid Leukemia (AML) Participants with AML received isatuximab 20 mg/kg IV infusion on Days 1, 8, and 15 of each Cycle (up to 2 treatment cycles, each cycle 28 days). Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.
B-ALL and T-ALL: Area Under the Concentration Time Curve (AUC) of Isatuximab Week 0 to Week 1	31703 mg*hour (h)/Liter (L) Standard Deviation 10048	29057 mg*hour (h)/Liter (L) Standard Deviation 8294	—
B-ALL and T-ALL: Area Under the Concentration Time Curve (AUC) of Isatuximab Week 0 to Week 5	299071 mg*hour (h)/Liter (L) Standard Deviation 127581	289167 mg*hour (h)/Liter (L) Standard Deviation 93095	—
B-ALL and T-ALL: Area Under the Concentration Time Curve (AUC) of Isatuximab Week 0 to Week 10	582686 mg*hour (h)/Liter (L) Standard Deviation 316749	540375 mg*hour (h)/Liter (L) Standard Deviation 233411	—

SECONDARY outcome

Timeframe: From Week 0 to Week 1, Week 0 to Week 3, and Week 0 to Week 8

Population: The PK population consisted of all participants from the AT population with at least 1 PK parameter available (isatuximab concentration). Only those participants with data available at specified timepoints were analyzed.

Plasma samples were collected at specified timepoints to determine the AUC of isatuximab.

Outcome measures

Outcome measures
Measure	B-cell Acute Lymphoblastic Leukemia (B-ALL) n=26 Participants Participants with B-ALL received isatuximab 20 mg/kg IV infusion QW for 4 weeks during the induction period (i.e., on Days 1, 8, 15, and 22) and Q2W during the consolidation period (i.e., on Days 29, 43, and 57. Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.	T-cell Acute Lymphoblastic Leukemia (T-ALL) Participants with T-ALL received isatuximab 20 mg/kg IV infusion QW for 4 weeks during the induction period (i.e., on Days 1, 8, 15, and 22) and Q2W during the consolidation period (i.e., on Days 29, 43, and 57. Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.	Acute Myeloid Leukemia (AML) Participants with AML received isatuximab 20 mg/kg IV infusion on Days 1, 8, and 15 of each Cycle (up to 2 treatment cycles, each cycle 28 days). Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.
AML: AUC of Isatuximab Week 0 to Week 1	28592 mg*h/L Standard Deviation 6858	—	—
AML: AUC of Isatuximab Week 0 to Week 3	130862 mg*h/L Standard Deviation 40827	—	—
AML: AUC of Isatuximab Week 0 to Week 8	291962 mg*h/L Standard Deviation 112222	—	—

SECONDARY outcome

Timeframe: Cycle 1 Day 8, Cycle 1 Day 15, Cycle 1 Day 22, Cycle 1 Day 29, Cycle 2 Day 43, Cycle 2 Day 57

Plasma samples were collected at specified timepoints to determine the Ctrough of isatuximab.

Outcome measures

Outcome measures
Measure	B-cell Acute Lymphoblastic Leukemia (B-ALL) n=27 Participants Participants with B-ALL received isatuximab 20 mg/kg IV infusion QW for 4 weeks during the induction period (i.e., on Days 1, 8, 15, and 22) and Q2W during the consolidation period (i.e., on Days 29, 43, and 57. Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.	T-cell Acute Lymphoblastic Leukemia (T-ALL) n=13 Participants Participants with T-ALL received isatuximab 20 mg/kg IV infusion QW for 4 weeks during the induction period (i.e., on Days 1, 8, 15, and 22) and Q2W during the consolidation period (i.e., on Days 29, 43, and 57. Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.	Acute Myeloid Leukemia (AML) Participants with AML received isatuximab 20 mg/kg IV infusion on Days 1, 8, and 15 of each Cycle (up to 2 treatment cycles, each cycle 28 days). Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.
B-ALL and T-ALL: Plasma Concentration Reached by Isatuximab Before Next Dose Administration (Ctrough) Cycle 1: Day 8	114 microgram/milliliter (mcg/mL) Standard Deviation 45.7	127 microgram/milliliter (mcg/mL) Standard Deviation 49.9	—
B-ALL and T-ALL: Plasma Concentration Reached by Isatuximab Before Next Dose Administration (Ctrough) Cycle 1: Day 15	272 microgram/milliliter (mcg/mL) Standard Deviation 118	263 microgram/milliliter (mcg/mL) Standard Deviation 103	—
B-ALL and T-ALL: Plasma Concentration Reached by Isatuximab Before Next Dose Administration (Ctrough) Cycle 1: Day 22	388 microgram/milliliter (mcg/mL) Standard Deviation 163	323 microgram/milliliter (mcg/mL) Standard Deviation 206	—
B-ALL and T-ALL: Plasma Concentration Reached by Isatuximab Before Next Dose Administration (Ctrough) Cycle 1: Day 29	475 microgram/milliliter (mcg/mL) Standard Deviation 174	426 microgram/milliliter (mcg/mL) Standard Deviation 209	—
B-ALL and T-ALL: Plasma Concentration Reached by Isatuximab Before Next Dose Administration (Ctrough) Cycle 2: Day 43	504 microgram/milliliter (mcg/mL) Standard Deviation 296	357 microgram/milliliter (mcg/mL) Standard Deviation NA Standard deviation (SD) could not be calculated for a single participant.	—
B-ALL and T-ALL: Plasma Concentration Reached by Isatuximab Before Next Dose Administration (Ctrough) Cycle 2: Day 57	531 microgram/milliliter (mcg/mL) Standard Deviation 224	478 microgram/milliliter (mcg/mL) Standard Deviation 261	—

SECONDARY outcome

Timeframe: Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1 and Cycle 2 Day 15

Plasma samples were collected at specified timepoints to determine the Ctrough of isatuximab.

Outcome measures

Outcome measures
Measure	B-cell Acute Lymphoblastic Leukemia (B-ALL) n=27 Participants Participants with B-ALL received isatuximab 20 mg/kg IV infusion QW for 4 weeks during the induction period (i.e., on Days 1, 8, 15, and 22) and Q2W during the consolidation period (i.e., on Days 29, 43, and 57. Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.	T-cell Acute Lymphoblastic Leukemia (T-ALL) Participants with T-ALL received isatuximab 20 mg/kg IV infusion QW for 4 weeks during the induction period (i.e., on Days 1, 8, 15, and 22) and Q2W during the consolidation period (i.e., on Days 29, 43, and 57. Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.	Acute Myeloid Leukemia (AML) Participants with AML received isatuximab 20 mg/kg IV infusion on Days 1, 8, and 15 of each Cycle (up to 2 treatment cycles, each cycle 28 days). Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.
AML: Plasma Concentration Reached by Isatuximab Before Next Dose Administration (Ctrough) Cycle 1: Day 8	126 mcg/mL Standard Deviation 41.0	—	—
AML: Plasma Concentration Reached by Isatuximab Before Next Dose Administration (Ctrough) Cycle 1: Day 15	217 mcg/mL Standard Deviation 60.6	—	—
AML: Plasma Concentration Reached by Isatuximab Before Next Dose Administration (Ctrough) Cycle 2: Day 1	115 mcg/mL Standard Deviation 94.2	—	—
AML: Plasma Concentration Reached by Isatuximab Before Next Dose Administration (Ctrough) Cycle 2: Day 15	420 mcg/mL Standard Deviation 205	—	—

SECONDARY outcome

Timeframe: At end of infusion on Cycle 1 Days 1 and 29

Ceoi is the plasma concentration observed at the end of intravenous infusion of isatuximab.

Outcome measures

Outcome measures
Measure	B-cell Acute Lymphoblastic Leukemia (B-ALL) n=27 Participants Participants with B-ALL received isatuximab 20 mg/kg IV infusion QW for 4 weeks during the induction period (i.e., on Days 1, 8, 15, and 22) and Q2W during the consolidation period (i.e., on Days 29, 43, and 57. Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.	T-cell Acute Lymphoblastic Leukemia (T-ALL) n=13 Participants Participants with T-ALL received isatuximab 20 mg/kg IV infusion QW for 4 weeks during the induction period (i.e., on Days 1, 8, 15, and 22) and Q2W during the consolidation period (i.e., on Days 29, 43, and 57. Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.	Acute Myeloid Leukemia (AML) Participants with AML received isatuximab 20 mg/kg IV infusion on Days 1, 8, and 15 of each Cycle (up to 2 treatment cycles, each cycle 28 days). Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.
B-ALL and T-ALL: Concentrations at the End of Infusion (Ceoi) of Isatuximab Cycle 1: Day 1	452 mcg/mL Standard Deviation 344	259 mcg/mL Standard Deviation 120	—
B-ALL and T-ALL: Concentrations at the End of Infusion (Ceoi) of Isatuximab Cycle 1: Day 29	835 mcg/mL Standard Deviation 366	745 mcg/mL Standard Deviation 330	—

SECONDARY outcome

Timeframe: At end of infusion on Cycle 1 Days 1 and 15

Ceoi is the plasma concentration observed at the end of intravenous infusion of isatuximab.

Outcome measures

Outcome measures
Measure	B-cell Acute Lymphoblastic Leukemia (B-ALL) n=27 Participants Participants with B-ALL received isatuximab 20 mg/kg IV infusion QW for 4 weeks during the induction period (i.e., on Days 1, 8, 15, and 22) and Q2W during the consolidation period (i.e., on Days 29, 43, and 57. Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.	T-cell Acute Lymphoblastic Leukemia (T-ALL) Participants with T-ALL received isatuximab 20 mg/kg IV infusion QW for 4 weeks during the induction period (i.e., on Days 1, 8, 15, and 22) and Q2W during the consolidation period (i.e., on Days 29, 43, and 57. Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.	Acute Myeloid Leukemia (AML) Participants with AML received isatuximab 20 mg/kg IV infusion on Days 1, 8, and 15 of each Cycle (up to 2 treatment cycles, each cycle 28 days). Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.
AML: Ceoi of Isatuximab Cycle 1: Day 1	363 mcg/mL Standard Deviation 110	—	—
AML: Ceoi of Isatuximab Cycle 1: Day 15	562 mcg/mL Standard Deviation 176	—	—

SECONDARY outcome

Timeframe: From screening until the study completion date, approximately 45 months

MRD assessment was performed centrally by next generation sequencing using clonoSEQ and T-cell receptor assays for B-ALL and T-ALL cohorts respectively. It was performed by flow cytometry for AML cohort. Number of participants with CR or CRi who achieved negative MRD in bone marrow and blood was analyzed. In AML indication, peripheral blood tissue is not representative of the tumor burden and cannot be used to assess MRD.

Outcome measures

Outcome measures
Measure	B-cell Acute Lymphoblastic Leukemia (B-ALL) n=13 Participants Participants with B-ALL received isatuximab 20 mg/kg IV infusion QW for 4 weeks during the induction period (i.e., on Days 1, 8, 15, and 22) and Q2W during the consolidation period (i.e., on Days 29, 43, and 57. Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.	T-cell Acute Lymphoblastic Leukemia (T-ALL) n=5 Participants Participants with T-ALL received isatuximab 20 mg/kg IV infusion QW for 4 weeks during the induction period (i.e., on Days 1, 8, 15, and 22) and Q2W during the consolidation period (i.e., on Days 29, 43, and 57. Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.	Acute Myeloid Leukemia (AML) n=14 Participants Participants with AML received isatuximab 20 mg/kg IV infusion on Days 1, 8, and 15 of each Cycle (up to 2 treatment cycles, each cycle 28 days). Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.
Number of Participants With Negative Minimal Residual Disease (MRD) Blood, 10^-6	3 Participants	1 Participants	—
Number of Participants With Negative Minimal Residual Disease (MRD) Bone marrow, 10^-6	0 Participants	2 Participants	0 Participants
Number of Participants With Negative Minimal Residual Disease (MRD) Bone marrow, 10^-3	—	—	0 Participants

SECONDARY outcome

Timeframe: From enrollment until the primary analysis completion date of 12 Sep 2022; the median duration of exposure was approximately 7 weeks

ORR:Percentage of participants with CR/CRi or partial response (PR) for blood and bone marrow disease based on NCCN guideline. CR: \<5% blasts in BMA with spicules; no circulating blasts (ALL)/no blasts with Auer rods (AML) or extramedullary disease, no lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/central nervous system involvement (ALL), trilineage hematopoiesis (ALL);ANC \>=1000/mcL; platelets \>100000/mcL; RBC transfusion independence. If the physician documented transfusion dependency related to study treatment;not to participant's underlying disease, CRi was reported. CRi met the same criteria as CR, except neutrophils and/or platelets recovery (ANC \<1000/mcL or platelets \<100000/mcL). PR: \>50% decrease in the sum of the product of the greatest perpendicular diameters of the mediastinal enlargement. For participants with a previous positive positron emission tomography (PET) scan, a post-treatment PET was to be positive in at least 1 previously involved site.

Outcome measures

Outcome measures
Measure	B-cell Acute Lymphoblastic Leukemia (B-ALL) n=25 Participants Participants with B-ALL received isatuximab 20 mg/kg IV infusion QW for 4 weeks during the induction period (i.e., on Days 1, 8, 15, and 22) and Q2W during the consolidation period (i.e., on Days 29, 43, and 57. Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.	T-cell Acute Lymphoblastic Leukemia (T-ALL) n=11 Participants Participants with T-ALL received isatuximab 20 mg/kg IV infusion QW for 4 weeks during the induction period (i.e., on Days 1, 8, 15, and 22) and Q2W during the consolidation period (i.e., on Days 29, 43, and 57. Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.	Acute Myeloid Leukemia (AML) n=23 Participants Participants with AML received isatuximab 20 mg/kg IV infusion on Days 1, 8, and 15 of each Cycle (up to 2 treatment cycles, each cycle 28 days). Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.
Overall Response Rate (ORR)	52.0 percentage of participants Interval 37.5 to 66.2	54.5 percentage of participants Interval 31.8 to 75.9	65.2 percentage of participants Interval 49.7 to 78.6

SECONDARY outcome

Timeframe: From first study treatment administration up to death due to any cause, a maximum of 45 months

Overall survival was defined as the time interval from the date of first study treatment administration to death from any cause. It was estimated using the Kaplan-Meier method. Confidence interval (CI) for Kaplan-Meier estimates were calculated with log-log transformation of survival function and methods of Brookmeyer and Crowley.

Outcome measures

Outcome measures
Measure	B-cell Acute Lymphoblastic Leukemia (B-ALL) n=25 Participants Participants with B-ALL received isatuximab 20 mg/kg IV infusion QW for 4 weeks during the induction period (i.e., on Days 1, 8, 15, and 22) and Q2W during the consolidation period (i.e., on Days 29, 43, and 57. Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.	T-cell Acute Lymphoblastic Leukemia (T-ALL) n=11 Participants Participants with T-ALL received isatuximab 20 mg/kg IV infusion QW for 4 weeks during the induction period (i.e., on Days 1, 8, 15, and 22) and Q2W during the consolidation period (i.e., on Days 29, 43, and 57. Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.	Acute Myeloid Leukemia (AML) n=23 Participants Participants with AML received isatuximab 20 mg/kg IV infusion on Days 1, 8, and 15 of each Cycle (up to 2 treatment cycles, each cycle 28 days). Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.
Overall Survival (OS)	12.09 months Interval 3.975 to NA indicates that the upper limit of CI was not estimable due to insufficient number of participants with events at study closure.	6.85 months Interval 2.201 to NA indicates that the upper limit of CI was not estimable due to insufficient number of participants with events at study closure.	9.40 months Interval 5.947 to NA indicates that the upper limit of CI was not estimable due to insufficient number of participants with events at study closure.

SECONDARY outcome

Timeframe: From study treatment administration up to the date of first documented disease progression or death due to any cause, a maximum of 45 months

EFS was defined as the time interval from the date of first study treatment administration to the date of the first of: completion or going off protocol induction/consolidation therapy without CR, relapse from CR, or death due to any cause, whichever occurred first. It was estimated using the Kaplan-Meier method. CI for Kaplan-Meier estimates are calculated with log-log transformation of survival function and methods of Brookmeyer and Crowley.

Outcome measures

Outcome measures
Measure	B-cell Acute Lymphoblastic Leukemia (B-ALL) n=25 Participants Participants with B-ALL received isatuximab 20 mg/kg IV infusion QW for 4 weeks during the induction period (i.e., on Days 1, 8, 15, and 22) and Q2W during the consolidation period (i.e., on Days 29, 43, and 57. Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.	T-cell Acute Lymphoblastic Leukemia (T-ALL) n=11 Participants Participants with T-ALL received isatuximab 20 mg/kg IV infusion QW for 4 weeks during the induction period (i.e., on Days 1, 8, 15, and 22) and Q2W during the consolidation period (i.e., on Days 29, 43, and 57. Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.	Acute Myeloid Leukemia (AML) n=23 Participants Participants with AML received isatuximab 20 mg/kg IV infusion on Days 1, 8, and 15 of each Cycle (up to 2 treatment cycles, each cycle 28 days). Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.
Event-Free Survival (EFS)	2.23 months Interval 1.413 to NA indicates that upper limit of CI was not estimable due to insufficient number of participants with events at study closure.	2.14 months Interval 1.347 to NA indicates that upper limit of CI was not estimable due to insufficient number of participants with events at study closure.	5.65 months Interval 1.347 to NA indicates that upper limit of CI was not estimable due to insufficient number of participants with events at study closure.

SECONDARY outcome

Timeframe: From first documented response up to the date of first documented disease progression or death due to any cause, a maximum of 45 months

Duration of response was defined as the time from the date of the first response to the date of first disease progression or death from any cause, whichever happens first. It was estimated using the Kaplan-Meier method. CI for Kaplan-Meier estimates are calculated with log-log transformation of survival function and methods of Brookmeyer and Crowley.

Outcome measures

Outcome measures
Measure	B-cell Acute Lymphoblastic Leukemia (B-ALL) n=13 Participants Participants with B-ALL received isatuximab 20 mg/kg IV infusion QW for 4 weeks during the induction period (i.e., on Days 1, 8, 15, and 22) and Q2W during the consolidation period (i.e., on Days 29, 43, and 57. Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.	T-cell Acute Lymphoblastic Leukemia (T-ALL) n=5 Participants Participants with T-ALL received isatuximab 20 mg/kg IV infusion QW for 4 weeks during the induction period (i.e., on Days 1, 8, 15, and 22) and Q2W during the consolidation period (i.e., on Days 29, 43, and 57. Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.	Acute Myeloid Leukemia (AML) n=14 Participants Participants with AML received isatuximab 20 mg/kg IV infusion on Days 1, 8, and 15 of each Cycle (up to 2 treatment cycles, each cycle 28 days). Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.
Duration of Response (DoR)	7.26 months Lower and upper limits of CI not estimable due to insufficient number of participants with events at study closure	1.18 months Interval 0.887 to Upper limit of CI not estimable due to insufficient number of participants with events at study closure	4.40 months Lower and upper limits of CI not estimable due to insufficient number of participants with events at study closure

SECONDARY outcome

Timeframe: Pre-dose on Day 1

Blood samples were collected to assess CD38 receptor density as a predictive biomarker. It was assessed across complete responders and non-complete responders. The Antibody Binding Capacity (ABC) was calculated using the following equation: ABC = 10\^(Logarithm(Mean Fluorescence Intensity)\*a+b) where "a" was the slope and "b" was the Y-intercept of the calibration curve equation. Specific and absolute quantitative values (specific antibody-binding capacity \[sABC\]) of binding of the selected antibodies were calculated after subtraction of the negative isotypic immunoglobulin G (IgG) control.

Outcome measures

Outcome measures
Measure	B-cell Acute Lymphoblastic Leukemia (B-ALL) n=25 Participants Participants with B-ALL received isatuximab 20 mg/kg IV infusion QW for 4 weeks during the induction period (i.e., on Days 1, 8, 15, and 22) and Q2W during the consolidation period (i.e., on Days 29, 43, and 57. Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.	T-cell Acute Lymphoblastic Leukemia (T-ALL) n=11 Participants Participants with T-ALL received isatuximab 20 mg/kg IV infusion QW for 4 weeks during the induction period (i.e., on Days 1, 8, 15, and 22) and Q2W during the consolidation period (i.e., on Days 29, 43, and 57. Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.	Acute Myeloid Leukemia (AML) n=23 Participants Participants with AML received isatuximab 20 mg/kg IV infusion on Days 1, 8, and 15 of each Cycle (up to 2 treatment cycles, each cycle 28 days). Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.
Cluster of Differentiation (CD)38 Receptor Density Blood immune cells (Natural Killer [NK] cells): CR/CRi	13506.2 sABC Standard Deviation 3018.6	22639.0 sABC Standard Deviation 1796.1	11220.3 sABC Standard Deviation 3764.6
Cluster of Differentiation (CD)38 Receptor Density Blood immune cells (NK cells): Non CR/CRi	16650.0 sABC Standard Deviation 851.4	33859.0 sABC Standard Deviation NA SD cannot be calculated for a single participant.	22530.0 sABC Standard Deviation 685.9
Cluster of Differentiation (CD)38 Receptor Density Blood blast cells: CR/CRi	20345.6 sABC Standard Deviation 23439.7	12780.0 sABC Standard Deviation 15559.2	19502.0 sABC Standard Deviation 20919.7
Cluster of Differentiation (CD)38 Receptor Density Blood blast cells: Non CR/CRi;	31080.0 sABC Standard Deviation 2397.1	22952.0 sABC Standard Deviation NA SD cannot be calculated for a single participant.	9815.0 sABC Standard Deviation 4203.0

SECONDARY outcome

Timeframe: Pre-dose on Day 15

Blood samples were collected to assess CD38 receptor occupancy as a pharmacodynamics marker. It was assessed across complete responders and non-complete responders. Multicolor flow cytometry assay was validated for CD38 receptor occupancy (CD38RO) quantification, based on the use of two murine monoclonal antibodies (MAbs), one competing with SAR650984 to determine the number of free CD38 receptors (MAb1) and one recognizing a different binding epitope on CD38 to measure the total number of receptors (MAb2) at the cell surface of the cancer cells. Cells were tagged with either MAb1 (Tube #1) or MAb2 (Tube #2). The percentage RO was calculated using the following equation: % CD38RO = \[(sABC MAb2 - sABC MAb1)/sABC MAb2\] X 100.

Outcome measures

Outcome measures
Measure	B-cell Acute Lymphoblastic Leukemia (B-ALL) n=25 Participants Participants with B-ALL received isatuximab 20 mg/kg IV infusion QW for 4 weeks during the induction period (i.e., on Days 1, 8, 15, and 22) and Q2W during the consolidation period (i.e., on Days 29, 43, and 57. Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.	T-cell Acute Lymphoblastic Leukemia (T-ALL) n=11 Participants Participants with T-ALL received isatuximab 20 mg/kg IV infusion QW for 4 weeks during the induction period (i.e., on Days 1, 8, 15, and 22) and Q2W during the consolidation period (i.e., on Days 29, 43, and 57. Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.	Acute Myeloid Leukemia (AML) n=23 Participants Participants with AML received isatuximab 20 mg/kg IV infusion on Days 1, 8, and 15 of each Cycle (up to 2 treatment cycles, each cycle 28 days). Participants received recommended isatuximab premedication as per protocol. Starting on Day 8, combination chemotherapies were added. Participants without documented disease progression at EOT visit who had not started treatment with another anticancer therapy received follow-up visits every 2 months until initiation of another anticancer therapy, disease progression, death, or final analysis cut-off date, whichever occurred first. Participants with documented disease progression/initiation of new anticancer treatment were followed for survival every 4 months until death or final analysis cut-off date, whichever occurred first.
CD38 Receptor Occupancy Blood plasma cells: CR/CRi	—	40.5 percent receptor occupancy Standard Deviation 30.4	—
CD38 Receptor Occupancy Blood plasma cells: Non CR/CRi;	44.0 percent receptor occupancy Standard Deviation NA SD cannot be calculated for a single participant.	55.0 percent receptor occupancy Standard Deviation NA SD cannot be calculated for a single participant.	—
CD38 Receptor Occupancy Blood NK cells: CR/CRi	55.6 percent receptor occupancy Standard Deviation 6.9	66.7 percent receptor occupancy Standard Deviation 2.1	—
CD38 Receptor Occupancy Blood NK cells: Non CR/CRi	61.3 percent receptor occupancy Standard Deviation 3.5	70.0 percent receptor occupancy Standard Deviation NA SD cannot be calculated for a single participant.	—

Adverse Events

B-cell Acute Lymphoblastic Leukemia (B-ALL)

Serious events: 19 serious events

Other events: 26 other events

Deaths: 17 deaths

T-cell Acute Lymphoblastic Leukemia (T-ALL)

Serious events: 12 serious events

Other events: 12 other events

Deaths: 8 deaths

Acute Myeloid Leukemia (AML)

Serious events: 17 serious events

Other events: 24 other events

Deaths: 18 deaths

All Participants

Serious events: 48 serious events

Other events: 62 other events

Deaths: 43 deaths

Serious adverse events

Other adverse events

Additional Information

Trial Transparency Team

Sanofi aventis recherche & développement

Phone: 800-633-1610

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
Publication restrictions are in place

Restriction type: OTHER