TriangleNCT03860844 · CITED IN SOURCE DOCUMENTS
Isatuximab in Combination With Chemotherapy in Pediatric Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia or Acute Myeloid Leukemia
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE2
- Status at capture
- TERMINATED
- Registry last update
- 2025-09-09
Primary Objective: Evaluate the anti-leukemic activity of isatuximab in combination with standard chemotherapies in pediatric participants of ages 28 days to less than 18 years with Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL) or Acute Myeloid Leukemia (AML) Secondary Objectives: * Safety and tolerability assessments * Assessment of infusion reactions (IRs) * Pharmacokinetics (PK) of isatuximab * Minimal residual disease * Overall response rate * Overall survival * Event free survival * Duration of response * Relationship between clinical effects and CD38 receptor density and occupancy
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What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Percentage of Participants With Complete Response (CR) Rate
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
Number of Participants With Infusion Reactions (IRs)
B-ALL and T-ALL: Area Under the Concentration Time Curve (AUC) of Isatuximab
AML: AUC of Isatuximab
B-ALL and T-ALL: Plasma Concentration Reached by Isatuximab Before Next Dose Administration (Ctrough)
AML: Plasma Concentration Reached by Isatuximab Before Next Dose Administration (Ctrough)
B-ALL and T-ALL: Concentrations at the End of Infusion (Ceoi) of Isatuximab
AML: Ceoi of Isatuximab
Number of Participants With Negative Minimal Residual Disease (MRD)
Overall Response Rate (ORR)
Overall Survival (OS)
Event-Free Survival (EFS)
Duration of Response (DoR)
Cluster of Differentiation (CD)38 Receptor Density
CD38 Receptor Occupancy
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- Inclusion criteria: * Participant 28 days to less than 18 years of age, at the time of signing the informed consent. * Participants must have had a confirmed diagnosis of relapsed Acute Lymphoblastic Leukemia (ALL) of T- or B-cell origin including T-lymphoblastic lymphoma (LBL), or relapsed Acute Myeloblastic Leukemia (AML) including participants with history of myelodysplasia. * Participants must have been previously treated for their disease and have relapsed or are refractory to most recent treatment. Participants in first or second relapse were eligible regardless of the remission duration. * Participants who had no more than 1 prior salvage therapy. * White Blood Cell (WBC) counts below 20 x10\^9/L on Day 1 before isatuximab administration Exclusion criteria: * Any serious active disease or co-morbid condition which, in the opinion of the Investigator, may interfere with the safety of the study treatment or the compliance with the study protocol. * Participants must have been off prior treatment with immunotherapy/investigational agents and chemotherapy for \>2 weeks and must have recovered from acute toxicity before the first study treatment administration. Exceptions were participants who needed to receive cytoreductive chemotherapy in order to decrease tumor burden (the study treatment may have started earlier if necessitated by the patient's medical condition (eg, rapidly progressive disease) following discussion with the Sponsor). * Prior stem cell transplant within 3 months and/or evidence of active systemic Graft versus Host Disease (GVHD) and/or immunosuppressive therapy for GVHD within 1 week before the first study treatment administration. * Participants with LBL with bone marrow blasts \<5%. * Participants with Burkitt-type ALL. * Acute leukemia with testicular or central nerve system involvement alone. * Participants who had developed therapy related acute leukemia. * Live vaccine(s) within 30 days prior to the first IMP administration or plans to receive such vaccines during the study until 90 days after the last IMP administration. * Participants with white blood cell count \> 50 x10\^9/L at the time of screening visit. * Participants who had been exposed to anti-CD38 therapies within 6 months prior to Day-1. The above information was not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
- healthy Volunteers
- false
- maximum Age
- 17 Years
- minimum Age
- 28 Days
- sex
- ALL
- std Ages
- CHILD
Treatment arms and interventions
- arm Groups
- description
- This arm includes participants from 3 cohorts: AML, T-ALL and B-ALL.; AML: Weekly dosing of isatuximab with induction chemotherapy. The therapy may be repeated one more cycle; ALL: (Includes T-ALL and B-ALL) Weekly dosing of isatuximab with induction chemotherapy, then biweekly dosing of isatuximab with consolidation chemotherapy.
- intervention Names
- Drug: Isatuximab
- Drug: Dexamethasone or equivalent
- Drug: Fludarabine
- Drug: Cytarabine
- Drug: Liposomal daunorubicin
- Drug: Daunorubicin (nonliposomal)
- Drug: Idarubicin
- Drug: Filgrastim or equivalent
- Drug: Mitoxantrone
- Drug: Doxorubicin
- Drug: Vincristine
- Drug: Pegaspargase (PEG) Asparaginase
- label
- Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
- description
- Pharmaceutical form: Concentrate for solution for intravenous infusion Route of administration: Intravenous
- name
- Isatuximab
- other Names
- SAR650984
- Sarclisa
- type
- DRUG
- arm Group Labels
- Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
- description
- Pharmaceutical form: Solution for injection or tablet Route of administration: Intravenous or oral
- name
- Dexamethasone or equivalent
- type
- DRUG
- arm Group Labels
- Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
- description
- Pharmaceutical form: Solution for injection Route of administration: Intravenous
- name
- Fludarabine
- type
- DRUG
- arm Group Labels
- Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
- description
- Pharmaceutical form: Solution for injection Route of administration: Intravenous
- name
- Cytarabine
- type
- DRUG
- arm Group Labels
- Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
- description
- Pharmaceutical form: Solution for injection Route of administration: Intravenous
- name
- Liposomal daunorubicin
- type
- DRUG
- arm Group Labels
- Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
- description
- Pharmaceutical form: Solution for injection Route of administration: Intravenous infusion
- name
- Daunorubicin (nonliposomal)
- type
- DRUG
- arm Group Labels
- Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
- description
- Pharmaceutical form: Solution for injection Route of administration: Intravenous
- name
- Idarubicin
- type
- DRUG
- arm Group Labels
- Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
- description
- Pharmaceutical form: Solution for injection Route of administration: Intravenous
- name
- Filgrastim or equivalent
- type
- DRUG
- arm Group Labels
- Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
- description
- Pharmaceutical form: Solution for injection Route of administration: Intravenous
- name
- Mitoxantrone
- type
- DRUG
- arm Group Labels
- Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
- description
- Pharmaceutical form: Solution for injection Route of administration: Intravenous
- name
- Doxorubicin
- type
- DRUG
- arm Group Labels
- Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
- description
- Pharmaceutical form: Solution for injection Route of administration: Intravenous
- name
- Vincristine
- type
- DRUG
- arm Group Labels
- Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
- description
- Pharmaceutical form: Solution for injection Route of administration: Intravenous infusion
- name
- Pegaspargase (PEG) Asparaginase
- type
- DRUG
Study design
- allocation
- NA
- intervention Model
- SINGLE_GROUP
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 67
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- 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).
- measure
- Percentage of Participants With Complete Response (CR) Rate
- time Frame
- From enrollment until the primary analysis completion date of 12 Sep 2022; the median duration of exposure was approximately 7 weeks
- secondary Outcomes
- description
- 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.
- measure
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
- 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)
- description
- 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.
- measure
- Number of Participants With Infusion Reactions (IRs)
- 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)
- description
- Plasma samples were collected at specified timepoints to determine the AUC of isatuximab.
- measure
- B-ALL and T-ALL: Area Under the Concentration Time Curve (AUC) of Isatuximab
- time Frame
- From Week 0 to Week 1, Week 0 to Week 5, and Week 0 to Week 10
- description
- Plasma samples were collected at specified timepoints to determine the AUC of isatuximab.
- measure
- AML: AUC of Isatuximab
- time Frame
- From Week 0 to Week 1, Week 0 to Week 3, and Week 0 to Week 8
- description
- Plasma samples were collected at specified timepoints to determine the Ctrough of isatuximab.
- measure
- B-ALL and T-ALL: Plasma Concentration Reached by Isatuximab Before Next Dose Administration (Ctrough)
- 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
- description
- Plasma samples were collected at specified timepoints to determine the Ctrough of isatuximab.
- measure
- AML: Plasma Concentration Reached by Isatuximab Before Next Dose Administration (Ctrough)
- time Frame
- Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1 and Cycle 2 Day 15
- description
- Ceoi is the plasma concentration observed at the end of intravenous infusion of isatuximab.
- measure
- B-ALL and T-ALL: Concentrations at the End of Infusion (Ceoi) of Isatuximab
- time Frame
- At end of infusion on Cycle 1 Days 1 and 29
- description
- Ceoi is the plasma concentration observed at the end of intravenous infusion of isatuximab.
- measure
- AML: Ceoi of Isatuximab
- time Frame
- At end of infusion on Cycle 1 Days 1 and 15
- description
- 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.
- measure
- Number of Participants With Negative Minimal Residual Disease (MRD)
- time Frame
- From screening until the study completion date, approximately 45 months
- description
- 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.
- measure
- Overall Response Rate (ORR)
- time Frame
- From enrollment until the primary analysis completion date of 12 Sep 2022; the median duration of exposure was approximately 7 weeks
- description
- 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.
- measure
- Overall Survival (OS)
- time Frame
- From first study treatment administration up to death due to any cause, a maximum of 45 months
- description
- 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.
- measure
- Event-Free Survival (EFS)
- 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
Full study description
- brief Summary
- Primary Objective: Evaluate the anti-leukemic activity of isatuximab in combination with standard chemotherapies in pediatric participants of ages 28 days to less than 18 years with Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL) or Acute Myeloid Leukemia (AML) Secondary Objectives: * Safety and tolerability assessments * Assessment of infusion reactions (IRs) * Pharmacokinetics (PK) of isatuximab * Minimal residual disease * Overall response rate * Overall survival * Event free survival * Duration of response * Relationship between clinical effects and CD38 receptor density and occupancy
- detailed Description
- The study included: * a screening period of up to (up to 3 weeks prior to the first study treatment administration); * a study treatment period \[Day 1 to Day 57 for Acute Lymphoblastic Leukemia (ALL); Day 1 to Day 22 for Acute Myeloid Leukemia (AML)\]; * the period of aplasia followed by a recovery period; * an end of treatment (EOT) visit \[within 30 days after hematological recovery; * a follow-up period (until final analysis cut off date).
Source references
Source notices and limitations
Discovery and provenance
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Preserved source evidence · Not medical advice