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

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)

An AE was defined as any untoward medical occurrence in a participant 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.

Time frame: 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)

Number of Participants With Infusion Reactions (IRs)

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.

Time frame: 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)

B-ALL and T-ALL: Area Under the Concentration Time Curve (AUC) of Isatuximab

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

Time frame: From Week 0 to Week 1, Week 0 to Week 5, and Week 0 to Week 10

AML: AUC of Isatuximab

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

Time frame: From Week 0 to Week 1, Week 0 to Week 3, and Week 0 to Week 8

B-ALL and T-ALL: Plasma Concentration Reached by Isatuximab Before Next Dose Administration (Ctrough)

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

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

AML: Plasma Concentration Reached by Isatuximab Before Next Dose Administration (Ctrough)

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

Time frame: Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1 and Cycle 2 Day 15

B-ALL and T-ALL: Concentrations at the End of Infusion (Ceoi) of Isatuximab

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

Time frame: At end of infusion on Cycle 1 Days 1 and 29

AML: Ceoi of Isatuximab

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

Time frame: At end of infusion on Cycle 1 Days 1 and 15

Number of Participants With Negative Minimal Residual Disease (MRD)

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.

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

Overall Response Rate (ORR)

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.

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

Overall Survival (OS)

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.

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

Event-Free Survival (EFS)

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.

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

Duration of Response (DoR)

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.

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

Cluster of Differentiation (CD)38 Receptor Density

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.

Time frame: Pre-dose on Day 1

CD38 Receptor Occupancy

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.

Time frame: Pre-dose on Day 15