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 |
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Recruitment Status :
Active, not recruiting
First Posted : March 4, 2019
Last Update Posted : February 3, 2023
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Sponsor:
Sanofi
Information provided by (Responsible Party):
Sanofi
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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
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Acute Lymphoblastic Leukemia Acute Myeloid Leukemia | 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 | Phase 2 |
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 : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 96 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | August 6, 2019 |
| Estimated Primary Completion Date : | May 22, 2023 |
| Estimated Study Completion Date : | May 22, 2023 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Familial acute myeloid leukemia with mutated CEBPA
Cytogenetically normal acute myeloid leukemia
Core binding factor acute myeloid leukemia
Drug Information available for:
Isatuximab
| Arm | Intervention/treatment |
|---|---|
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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.
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Drug: Montelukast
Pharmaceutical form: tablet Route of administration: oral Drug: Isatuximab Pharmaceutical form: Solution for injection Route of administration: Intravenous
Other Names:
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 |
Primary Outcome Measures :
- 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
Secondary Outcome Measures :
- 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.
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| Ages Eligible for Study: | 28 Days to 17 Years (Child) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03860844
Locations
Show 49 study locations
Sponsors and Collaborators
Sanofi
Investigators
| Study Director: | Clinical Sciences & Operations | Sanofi |
| Responsible Party: | Sanofi |
| ClinicalTrials.gov Identifier: | NCT03860844 |
| Other Study ID Numbers: |
ACT15378 PIP - 2018-002697-45 U1111-1202-1096 ( Other Identifier: UTN ) |
| First Posted: | March 4, 2019 Key Record Dates |
| Last Update Posted: | February 3, 2023 |
| Last Verified: | February 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| 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://vivli.org |
| 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 |
Keywords provided by Sanofi:
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Anti-CD38 monoclonal antibody |
Additional relevant MeSH terms:
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Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Cytarabine Dexamethasone Cyclophosphamide Doxorubicin |
Methotrexate Fludarabine Etoposide Vincristine Daunorubicin Asparaginase Mitoxantrone Idarubicin Hydroxyurea Pegaspargase Montelukast Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents |