Isatuximab in Combination With Chemotherapy in Pediatric Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia or Acute Myeloid Leukemia
Condition: Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
Intervention: Isatuximab; Dexamethasone or equivalent; Fludarabine; Cytarabine; Liposomal daunorubicin; Daunorubicin (nonliposomal); Idarubicin; Filgrastim or equivalent; Mitoxantrone; Doxorubicin; Vincristine; Pegaspargase (PEG) Asparaginase; Cyclophosphamide; Etoposide; Methotrexate; L - Asparginase; Hydroxyurea; L - Asparaginase (Erwinase)
Intervention description: Pharmaceutical form: Concentrate for solution for intravenous infusion Route of administration: Intravenous; Pharmaceutical form: Solution for injection or tablet Route of administration: Intravenous or oral; Pharmaceutical form: Solution for injection Route of administration: Intravenous; Pharmaceutical form: Solution for injection Route of administration: Intravenous; Pharmaceutical form: Solution for injection Route of administration: Intravenous; Pharmaceutical form: Solution for injection Route of administration: Intravenous infusion; Pharmaceutical form: Solution for injection Route of administration: Intravenous; Pharmaceutical form: Solution for injection Route of administration: Intravenous; Pharmaceutical form: Solution for injection Route of administration: Intravenous; Pharmaceutical form: Solution for injection Route of administration: Intravenous; Pharmaceutical form: Solution for injection Route of administration: Intravenous; Pharmaceutical form: Solution for injection Route of administration: Intravenous infusion; Pharmaceutical form: Solution for injection Route of administration: Intravenous; Pharmaceutical form: Solution for injection Route of administration: Intravenous infusion; Pharmaceutical form: Solution for injection Route of administration: Intravenous infusion; Pharmaceutical form: Solution for injection Route of administration: Intramuscular; Pharmaceutical form: Solution for injection Route of administration: PO; Pharmaceutical form: Solution for injection Route of administration: Intramuscular
Intervention MeSH terms: Cytarabine; Dexamethasone; Cyclophosphamide; Doxorubicin; Methotrexate; Fludarabine; Etoposide; Vincristine; Daunorubicin; Asparaginase; Mitoxantrone; Idarubicin; Hydroxyurea; Pegaspargase
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 67.0
Sex: All
Minimum age: 28 Days
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Anti-CD38 monoclonal antibody

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
    

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.