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

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ClinicalTrials.gov Identifier: NCT03860844
Recruitment Status : Recruiting
First Posted : March 4, 2019
Last Update Posted : June 8, 2021
Sponsor:
Information provided by (Responsible Party):
Sanofi

Tracking Information
First Submitted Date  ICMJE February 21, 2019
First Posted Date  ICMJE March 4, 2019
Last Update Posted Date June 8, 2021
Actual Study Start Date  ICMJE August 6, 2019
Estimated Primary Completion Date August 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 14, 2020)
  • Complete Response (CR) rate in acute myeloid leukemia (AML) cohort [ Time Frame: Baseline to Day 22 ]
    CR rate is defined as the proportion of participants with CR or CRi, in AML
  • Complete Response (CR) rate in B-cell acute lymphoblastic leukemia (B-ALL) cohort [ Time Frame: Baseline to Day 57 ]
    Morphological CR rate defined as the proportion of participants with CR or CRi
  • Complete Response (CR) rate in T-cell acute lymphoblastic leukemia (T-ALL) cohort [ Time Frame: Baseline to Day 57 ]
    Morphological CR rate defined as the proportion of participants with CR or CRi
Original Primary Outcome Measures  ICMJE
 (submitted: February 28, 2019)
  • Complete Response (CR) rate in acute myeloid leukemia (AML) cohort [ Time Frame: Baseline to Day 22 ]
    Morphological CR rate defined as the proportion of participants with CR or CRi (CR with incomplete peripheral recovery)
  • Complete Response (CR) rate in B-cell acute lymphoblastic leukemia (B-ALL) cohort [ Time Frame: Baseline to Day 57 ]
    Morphological CR rate defined as the proportion of participants with CR or CRi
  • Complete Response (CR) rate in T-cell acute lymphoblastic leukemia (T-ALL) cohort [ Time Frame: Baseline to Day 57 ]
    Morphological CR rate defined as the proportion of participants with CR or CRi
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 14, 2020)
  • Safety and tolerability assessments [ Time Frame: Baseline to approximately 3 months ]
    Number of adverse events and serious adverse events
  • Assessment of infusion reactions [ Time Frame: Time from isatuximab infusion to resolution (approximately 2 days) ]
    Incidence and severity of infusion reactions
  • Pharmacokinetics of isatuximab: Cmax [ Time Frame: Day 1 to 30 days after hematological recovery ]
    Maximum observed concentration (Cmax)
  • Pharmacokinetics of isatuximab: Ctrough [ Time Frame: Day 1 to 30 days after hematological recovery ]
    Concentration observed just before treatment administration during repeated dosing (Ctrough)
  • Pharmacokinetics of isatuximab: AUC [ Time Frame: Day 1 to 30 days after hematological recovery ]
    Partial area under the serum concentration time curve: AUC
  • Minimal residual disease [ Time Frame: On day 43 ]
    Estimation of minimal residual disease in participants achieving CR or CRi
  • Overall response rate [ Time Frame: On day 43 ]
    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
  • Overall survival [ Time Frame: Baseline to approximately 3 months ]
    Overall survival is defined as the time interval from the date of first study treatment administration to death from any cause
  • Event free survival [ Time Frame: Baseline to approximately 3 months ]
    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
  • Duration of response [ Time Frame: Time from the first response to the first disease progression or death ]
    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
  • Change in CD38 receptor density and occupancy [ Time Frame: Baseline to Day 15 ]
    CD38 receptor density will be assessed at baseline and CD38 receptor occupancy at Day 15 and correlated with clinical endpoints.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 28, 2019)
  • Safety and tolerability assessments: Adverse events [ Time Frame: Baseline to approximately 3 months ]
    Number of adverse events and serious adverse events
  • Assessment of infusion reactions [ Time Frame: Time from isatuximab infusion to resolution (approximately 2 days) ]
    Incidence and severity of infusion reactions
  • Pharmacokinetics of isatuximab: Cmax [ Time Frame: Day 1 to 30 days after hematological recovery ]
    Maximum observed concentration (Cmax)
  • Pharmacokinetics of isatuximab: Ctrough [ Time Frame: Day 1 to 30 days after hematological recovery ]
    Concentration observed just before treatment administration during repeated dosing (Ctrough)
  • Pharmacokinetics of isatuximab: AUC [ Time Frame: Day 1 to 30 days after hematological recovery ]
    Partial area under the serum concentration time curve: AUC
  • Minimal residual disease [ Time Frame: On day 43 ]
    Estimation of minimal residual disease in participants achieving CR or CRi
  • Overall response rate [ Time Frame: On day 43 ]
    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
  • Overall survival [ Time Frame: Baseline to approximately 3 months ]
    Overall survival is defined as the time interval from the date of first study treatment administration to death from any cause
  • Event free survival [ Time Frame: Baseline to approximately 3 months ]
    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
  • Duration of response [ Time Frame: Time from the first response to the first disease progression or death, up to Month 42 ]
    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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Isatuximab in Combination With Chemotherapy in Pediatric Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia or Acute Myeloid Leukemia
Official Title  ICMJE 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
Brief Summary

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).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
Intervention  ICMJE
  • Drug: Montelukast
    Pharmaceutical form: tablet Route of administration: oral
  • Drug: Isatuximab
    Pharmaceutical form: Solution for injection Route of administration: Intravenous
    Other Names:
    • SAR650984
    • Sarclisa
  • Drug: Dexamethasone
    Pharmaceutical form: Solution for injection or tablet Route of administration: Intravenous or oral
  • Drug: Fludarabine
    Pharmaceutical form: Solution for injection Route of administration: Intravenous
  • Drug: Cytarabine
    Pharmaceutical form: Solution for injection Route of administration: Intravenous
  • Drug: Liposomal daunorubicin
    Pharmaceutical form: Solution for injection Route of administration: Intravenous
  • Drug: Daunorubicin
    Pharmaceutical form: Solution for injection Route of administration: Intravenous
  • Drug: Idarubicin
    Pharmaceutical form: Solution for injection Route of administration: Intravenous
  • Drug: Filgrastim
    Pharmaceutical form: Solution for injection Route of administration: Intravenous
  • Drug: Mitoxantrone
    Pharmaceutical form: Solution for injection Route of administration: Intravenous
  • Drug: Doxorubicin
    Pharmaceutical form: Solution for injection Route of administration: Intravenous
  • Drug: Vincristine
    Pharmaceutical form: Solution for injection Route of administration: Intravenous
  • Drug: PEG Asparaginase
    Pharmaceutical form: Solution for injection Route of administration: Intravenous
  • Drug: Cyclophosphamide
    Pharmaceutical form: Solution for injection Route of administration: Intravenous
  • Drug: Etoposide
    Pharmaceutical form: Solution for injection Route of administration: Intravenous
  • Drug: Methotrexate
    Pharmaceutical form: Solution for injection Route of administration: Intravenous
  • Drug: L - Asparginase
    Pharmaceutical form: Solution for injection Route of administration: Intramuscular
  • Drug: Hydroxyurea
    Pharmaceutical form: Solution for injection Route of administration: Intravenous
  • Drug: L - Asparaginase (Erwinase)
    Pharmaceutical form: Solution for injection Route of administration: Intramuscular
  • Drug: Tocilizumab
    Pharmaceutical form: Solution for injection Route of administration: Intravenous
Study Arms  ICMJE Experimental: Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia
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.
Interventions:
  • Drug: Montelukast
  • Drug: Isatuximab
  • Drug: Dexamethasone
  • Drug: Fludarabine
  • Drug: Cytarabine
  • Drug: Liposomal daunorubicin
  • Drug: Daunorubicin
  • Drug: Idarubicin
  • Drug: Filgrastim
  • Drug: Mitoxantrone
  • Drug: Doxorubicin
  • Drug: Vincristine
  • Drug: PEG Asparaginase
  • Drug: Cyclophosphamide
  • Drug: Etoposide
  • Drug: Methotrexate
  • Drug: L - Asparginase
  • Drug: Hydroxyurea
  • Drug: L - Asparaginase (Erwinase)
  • Drug: Tocilizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 14, 2019)
96
Original Estimated Enrollment  ICMJE
 (submitted: February 28, 2019)
104
Estimated Study Completion Date  ICMJE August 2023
Estimated Primary Completion Date August 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Trial Transparency email recommended (Toll free number for US & Canada) 800-633-1610 ext option 6 Contact-US@sanofi.com
Listed Location Countries  ICMJE Argentina,   Belgium,   Brazil,   Canada,   Czechia,   Denmark,   Finland,   France,   Germany,   Greece,   Hungary,   Italy,   Korea, Republic of,   Mexico,   Netherlands,   Norway,   Peru,   Portugal,   Sweden,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03860844
Other Study ID Numbers  ICMJE ACT15378
PIP - 2018-002697-45
U1111-1202-1096 ( Other Identifier: UTN )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://www.clinicalstudydatarequest.com/
Responsible Party Sanofi
Study Sponsor  ICMJE Sanofi
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Sciences & Operations Sanofi
PRS Account Sanofi
Verification Date June 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP