Clinical Trials /

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

NCT03860844

Description:

Primary Objective: To 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

Related Conditions:
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
  • T-Cell Lymphoblastic Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Isatuximab in Combination With Chemotherapy in Pediatric Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia or Acute Myeloid Leukemia
  • Official Title: Open-label, Single-arm Trial to Evaluate Antitumor Activity, Safety, and Pharmacokinetics of Isatuximab Used in Combination With Chemotherapy in Pediatric Patients From 28 Days to Less Than 18 Years of Age With Relapsed/Refractory B or T Acute Lymphoblastic Leukemia or Acute Myeloid Leukemia in First or Second Relapse

Clinical Trial IDs

  • ORG STUDY ID: ACT15378
  • SECONDARY ID: PIP - 2018-002697-45
  • SECONDARY ID: U1111-1202-1096
  • NCT ID: NCT03860844

Conditions

  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
MontelukastAcute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
IsatuximabSAR650984, SarclisaAcute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
DexamethasoneAcute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
FludarabineAcute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
CytarabineAcute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
Liposomal daunorubicinAcute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
DaunorubicinAcute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
IdarubicinAcute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
FilgrastimAcute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
MitoxantroneAcute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
DoxorubicinAcute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
VincristineAcute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
PEG AsparaginaseAcute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
CyclophosphamideAcute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
EtoposideAcute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
MethotrexateAcute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
L - AsparginaseAcute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
HydroxyureaAcute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
L - Asparaginase (Erwinase)Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
TocilizumabAcute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia

Purpose

Primary Objective: To 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 will include a screening period of up to 21 days (Day -21 to -1), a study treatment
      period [Day 1 to Day 57 for Acute Lymphoblastic Leukemia (ALL); Day 1 to Day 22 for Acute
      Myeloid Leukemia (AML)], a recovery period (until an end of treatment visit [within 30 days
      after hematological recovery]) and a follow-up period (until final analysis cut off date).
    

Trial Arms

NameTypeDescriptionInterventions
Acute Myeloid Leukemia (AML) and Acute Lymphoblastic LeukemiaExperimentalThis 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.
  • Montelukast
  • Isatuximab
  • Dexamethasone
  • Fludarabine
  • Cytarabine
  • Liposomal daunorubicin
  • Daunorubicin
  • Idarubicin
  • Filgrastim
  • Mitoxantrone
  • Doxorubicin
  • Vincristine
  • PEG Asparaginase
  • Cyclophosphamide
  • Etoposide
  • Methotrexate
  • L - Asparginase
  • Hydroxyurea
  • L - Asparaginase (Erwinase)
  • Tocilizumab

Eligibility Criteria

        Inclusion criteria:

          -  Participant must be 28 days to less than 18 years of age, at the time of signing the
             informed consent.

          -  Participants must have 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 be previously treated for their disease and have relapsed or are
             refractory to most recent treatment. Participants in first or second relapse will be
             eligible regardless of the remission duration.

          -  Participants with no more than 1 prior salvage therapy.

          -  WBC counts below 20 x109/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 are participants who need
             to receive cytoreductive chemotherapy in order to decrease tumor burden (the study
             treatment may start 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 have 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 x109/L at the time of screening visit.

          -  Participants who have been exposed to anti-CD38 therapies within 6 months prior to
             Day-1.

        The above information is not intended to contain all considerations relevant to a patient's
        potential participation in a clinical trial.
      
Maximum Eligible Age:17 Years
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Complete Response (CR) rate in acute myeloid leukemia (AML) cohort
Time Frame:Baseline to Day 22
Safety Issue:
Description:CR rate is defined as the proportion of participants with CR or CRi, in AML

Secondary Outcome Measures

Measure:Safety and tolerability assessments
Time Frame:Baseline to approximately 3 months
Safety Issue:
Description:Number of adverse events and serious adverse events
Measure:Assessment of infusion reactions
Time Frame:Time from isatuximab infusion to resolution (approximately 2 days)
Safety Issue:
Description:Incidence and severity of infusion reactions
Measure:Pharmacokinetics of isatuximab: Cmax
Time Frame:Day 1 to 30 days after hematological recovery
Safety Issue:
Description:Maximum observed concentration (Cmax)
Measure:Pharmacokinetics of isatuximab: Ctrough
Time Frame:Day 1 to 30 days after hematological recovery
Safety Issue:
Description:Concentration observed just before treatment administration during repeated dosing (Ctrough)
Measure:Pharmacokinetics of isatuximab: AUC
Time Frame:Day 1 to 30 days after hematological recovery
Safety Issue:
Description:Partial area under the serum concentration time curve: AUC
Measure:Minimal residual disease
Time Frame:On day 43
Safety Issue:
Description:Estimation of minimal residual disease in participants achieving CR or CRi
Measure:Overall response rate
Time Frame:On day 43
Safety Issue:
Description:The overall response rate is defined as the proportion of participants with CR or CRi for blood and bone marrow disease; Partial response (PR) based on the National Comprehensive Cancer Network (NCCN) guideline will be considered
Measure:Overall survival
Time Frame:Baseline to approximately 3 months
Safety Issue:
Description:Overall survival is defined as the time interval from the date of first study treatment administration to death from any cause
Measure:Event free survival
Time Frame:Baseline to approximately 3 months
Safety Issue:
Description:Event free survival is 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
Measure:Duration of response
Time Frame:Time from the first response to the first disease progression or death
Safety Issue:
Description:Duration of response is 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
Measure:Change in CD38 receptor density and occupancy
Time Frame:Baseline to Day 15
Safety Issue:
Description:CD38 receptor density will be assessed at baseline and CD38 receptor occupancy at Day 15 and correlated with clinical endpoints.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sanofi

Trial Keywords

  • Anti-CD38 monoclonal antibody

Last Updated

April 8, 2021