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 MedDRA version: 21.0 Level: PT Classification code 10000846 Term: Acute lymphocytic leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cyst
Conditions
Sponsors
Sanofi-aventis recherche & developpement
Eligibility
Sex/Gender
All
Inclusion 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. Are the trial subjects under 18? yes Number of subjects for this age range: 128 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main 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 Objective: - 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;Primary end point(s): 1) Complete Response (CR) rate in Acute myeloid leukemia (AML) cohort: CR rate is defined as the proportion of participants with CR or CRi, in AML 2) Complete Response (CR) rate in B-cell Acute lymphoblastic leukemia (B-ALL) cohort: Morphological CR rate defined as the proportion of participants with CR or CRi 3) Complete Response (CR) rate in T-cell Acute lymphoblastic leukemia (T-ALL) cohort: Morphological CR rate defined as the proportion of participants with CR or CRi;Timepoint(s) of evaluation of this end point: 1) Baseline to Day 22 2) and 3) Baseline to Day 57 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Safety and tolerability assessments: Number of adverse events and serious adverse events 2) Assessment of infusion reactions: Incidence and severity of infusion reactions 3) Pharmacokinetics of isatuximab (Cmax) : Maximum observed concentration (Cmax) 4) Pharmacokinetics of isatuximab (Ctrough): Concentration observed just before treatment administration during repeated dosing (Ctrough) 5) Pharmacokinetics of isatuximab (AUC): Partial area under the serum concentration time curve (AUC) 6) Minimal residual disease: Estimation of minimal residual disease in participants achieving CR or CRi 7) Overall response rate: 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 in case of lymphomatous extramedullary disease for T ALL participants 8) Overall survival: Overall survival defined as the time interval from the date of first study treatment administration to death from any cause 9) Event free survival: 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 10) Duration of Response: 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 11) Change in CD38 receptor density and occupancy: CD38 receptor density will be assessed at baseline and CD38 receptor occupancy at Day 15 and correlated with clinical endpoints.;Timepoint(s) of evaluation of this end point: 1), 8) and 9) Baseline to approximately 3 months 2) Time from isatuximab infusion to resolution (approximately 2 days) 3) to 5) Day 1 to 30 days after hematological recovery 6), 7) On day 43 10) Time from | — |
Countries
Argentina, Belgium, Brazil, Canada, Czechia, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Italy, Korea, Republic of, Mexico, Netherlands, Norway, Portugal, Sweden, United States
Contacts
Public ContactClinical Study Unit
Sanofi AB
Outcome results
None listed