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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT06508489
Registration number
NCT06508489
Ethics application status
Date submitted
27/06/2024
Date registered
18/07/2024
Date last updated
29/06/2025
Titles & IDs
Public title
A Study to Investigate Natural Killer Cell Engager (SAR443579) With Different Agents in Participants With Hematological Malignancies
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Scientific title
A Phase 1/Phase 2, Randomized, Open-label, Multi Cohort, Multi Center, Study Assessing the Safety, Tolerability and Preliminary Efficacy of SAR443579 a Natural Killer Cell Engager (NKCE) Targeting CD123, Administered With Different Agents in Participants With CD123 Expressing Hematological Malignancies
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Secondary ID [1]
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U1111-1280-6173
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Secondary ID [2]
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TCD17796
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukemia
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Condition category
Condition code
Cancer
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Leukaemia - Acute leukaemia
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Cancer
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Leukaemia - Chronic leukaemia
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Other - SAR443579
Treatment: Drugs - venetoclax
Treatment: Drugs - azacitidine
Experimental: Substudy 01: SAR443579 + azacitidine + venetoclax - Part 1: Safety run-in: SAR443579 treatment will begin with an identified starting dose. Safety run-in will proceed according to the incidence of DLTs.
Treatment: Other: SAR443579
Pharmaceutical form: Powder for solution for infusion Route of administration: intravenous infusion
Treatment: Drugs: venetoclax
Pharmaceutical form :Film coated tablet Route of administration: oral
Treatment: Drugs: azacitidine
Pharmaceutical form: Lyophilized powder for suspension for injection Route of administration: intravenous or subcutaneous
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Intervention code [1]
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Treatment: Other
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Intervention code [2]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Number of participants with adverse events (AEs)/serious adverse events (SAEs)/adverse events of special interest (AESIs), laboratory abnormalities
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Assessment method [1]
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Timepoint [1]
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Day 1 to 30 days after the last administration of study treatment
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Primary outcome [2]
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Substudy 01: Incidence of dose limiting toxicities (DLTs) (escalation part)
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Assessment method [2]
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Timepoint [2]
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Day 1 to Day 28
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Primary outcome [3]
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Substudy 01: Complete Remission (CR) rate (optimization part)
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Assessment method [3]
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Proportion of participants who have a CR (Complete Remission) determined by the Investigator according to 2022 European Leukemia Net (ELN) recommendations for diagnosis and management of AML
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Timepoint [3]
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Day 1 to 30 days after the last administration of study treatment
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Primary outcome [4]
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Substudy 01: Complete Remission (CR) rate (expansion part)
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Assessment method [4]
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Proportion of participants who have a CR (Complete Remission) determined by the Investigator according to 2022 European Leukemia Net (ELN) recommendations for diagnosis and management of AML
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Timepoint [4]
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Day 1 up to 6 months
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Secondary outcome [1]
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Number of participants with treatment emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interest (AESIs) and clinically significant laboratory abnormalities (expansion part)
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Assessment method [1]
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According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) V 5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS)
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Timepoint [1]
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Day 1 to 30 days after the last administration of study treatment
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Secondary outcome [2]
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Incidence of anti-drug anti body (ADA) against SAR443579
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Assessment method [2]
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Timepoint [2]
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Day 1 to 30 days after the last administration of study treatment
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Secondary outcome [3]
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Substudy 01: Percentage of participants with Minimal residual disease (expansion part)
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Assessment method [3]
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As defined by 2022 ELN recommendations for AML
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Timepoint [3]
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Day 1 up to 6 months
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Secondary outcome [4]
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Substudy 01: Pharmacokinetic (PK) parameter of SAR443579: Ctrough
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Assessment method [4]
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Concentrations observed at the end the dosing period during repeated administration for SAR443579
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Timepoint [4]
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Day 1 up to 10 cycles (each cycle 28 days)
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Secondary outcome [5]
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Substudy 01: PK parameter of venetoclax: Cmax
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Assessment method [5]
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Maximum concentration observed for venetoclax
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Timepoint [5]
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Day 1 to Day 28
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Secondary outcome [6]
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Substudy 01: PK parameter of azacitidine: Cmax
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Assessment method [6]
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Maximum concentration observed for azacitidine
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Timepoint [6]
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Day 1 to Day 28
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Secondary outcome [7]
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Substudy 01: PK parameter of venetoclax: AUC
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Assessment method [7]
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Area under the blood concentration versus time curve extrapolated to infinity for venetoclax
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Timepoint [7]
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Day 1 to Day 28
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Secondary outcome [8]
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Substudy 01: PK parameter of azacitidine: AUC
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Assessment method [8]
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Area under the blood concentration versus time curve extrapolated to infinity for azacitidine
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Timepoint [8]
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Day 1 to Day 28
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Secondary outcome [9]
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Substudy 01: Composite Complete Remission (CRc) rate
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Assessment method [9]
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Proportion of participants who have a CR (Complete Remission) + CRh (complete remission with partial hematologic recovery) + CRi (Complete Remission with Incomplete Hematologic Recovery) determined by the Investigator according to 2022 European Leukemia Net (ELN) recommendations for diagnosis and management of AML. (CRc = CR + CRh + CRi)
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Timepoint [9]
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Day 1 up to 6 months
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Secondary outcome [10]
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Substudy 01: Overall response rate (expansion part)
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Assessment method [10]
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Proportion of participants who have a CR or CRi or CRh or PR or MLFS (morphological leukemia-free state) according to the 2022 ELN criteria.
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Timepoint [10]
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Day 1 up to 6 months
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Secondary outcome [11]
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Substudy 01: Duration of CR (expansion part)
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Assessment method [11]
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Defined as the time interval from the first documented evidence of CR until disease relapse as per 2022 ELN recommendations or death due to any cause, whichever comes first
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Timepoint [11]
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Day 1 up to 24 months after the last administration from study treatment
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Secondary outcome [12]
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Substudy 01: Duration of CRc (expansion part)
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Assessment method [12]
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Defined as the time interval from first documented evidence of CRc (CR, CRh or CRi) until disease relapse as per 2022 ELN recommendations or death due to any cause, whichever comes first
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Timepoint [12]
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Day 1 up to 24 months after the last administration from study treatment
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Secondary outcome [13]
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Substudy 01: Duration of overall response (expansion part)
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Assessment method [13]
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Defined as the time from the first documented evidence of CR or CRi or CRh or PR or MLFS until disease relapse as per 2022 ELN recommendations or death due to any cause, whichever comes first
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Timepoint [13]
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Day 1 up to 24 months after the last administration from study treatment
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Secondary outcome [14]
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Substudy 01: Alternative CR rate (expansion part)
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Assessment method [14]
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Defined as the proportion of participants with CR+CRh (complete remission with partial hematological recovery)
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Timepoint [14]
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Day 1 up to 6 months
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Secondary outcome [15]
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Substudy 01: Duration of alternative CR (expansion part)
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Assessment method [15]
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Defined as the time from the first documented evidence of CR or CRh until disease relapse as per 2022 ELN recommendations or death due to any cause, whichever comes first
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Timepoint [15]
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Day 1 up to 24 months after the last administration from study treatment
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Secondary outcome [16]
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Substudy 01: Event-free survival (EFS) (expansion part)
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Assessment method [16]
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Defined as the time interval from the first day of treatment assignment to the date of earliest evidence of relapse, treatment failure, or death
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Timepoint [16]
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Day 1 up to 24 months after the last administration from study treatment
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Secondary outcome [17]
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Substudy 01: Overall survival (expansion part)
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Assessment method [17]
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Defined as time interval from the first day of treatment assignment to death from any cause
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Timepoint [17]
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Day 1 up to 24 months after the last administration from study treatment
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Secondary outcome [18]
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Substudy 01: Rate of hematopoietic stem cell transplantation (HSCT) procedures immediately following study treatment administration but prior to subsequent therapy for treatment of AML (all parts)
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Assessment method [18]
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The HSCT rate is defined as the proportion of such participants who undergo HSCT through study treatment but before subsequent therapy, among the safety/exposed population
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Timepoint [18]
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Day 1 up to 24 months after the last administration from study treatment
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Secondary outcome [19]
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Substudy 01: Time to treatment failure (TTF) (expansion part)
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Assessment method [19]
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Defined as the time from first day of treatment assignment to discontinuation for any reason excluding remission, for example relapsed disease, refractory disease, unacceptable AE, participant preference or death
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Timepoint [19]
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Day 1 up to 24 months after the last administration from study treatment
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Secondary outcome [20]
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Substudy 01: Rate of conversion from transfusion dependence to transfusion independence (all parts)
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Assessment method [20]
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The transfusion dependency (TD) at baseline is based on the receipt of any red blood cell or platelets transfusions within at least 28 days prior to the start of study treatment. For post baseline treatment, transfusion independency (TI) will be defined as the absence of transfusion during any 56 consecutive day period during treatment.
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Timepoint [20]
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Day 1 to Day 56
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Secondary outcome [21]
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Substudy 01: Rate of participants who are transfusion independent at baseline and remain independent during 56-day post-baseline period (all parts)
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Assessment method [21]
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Transfusion independency (TI) will be defined as the absence of transfusion during any 56 consecutive day period during treatment.
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Timepoint [21]
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Day 1 to Day 56
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Eligibility
Key inclusion criteria
- Participants with CD123-expressing hematological neoplasm per the 5th edition of the WHO Classification of Hematolymphoid Tumors.
Substudy 01:
* Participants must be =18 years of age
* Confirmed diagnosis of Acute Myeloid Leukemia
* Ineligible for intensive chemotherapy. Ineligible for intensive chemotherapy is defined by the following criteria:
A) = 75 years of age, OR
B) 18 to 74 years of age and meeting one or more of the following:
1. Eastern Cooperative Oncology Group (ECOG) performance status 2-3.
2. Cardiac history of congestive heart failure (CHF) requiring treatment or left ventricular ejection fraction (LVEF) =50% or symptomatic coronary heart disease confirmed by coronarography or cardiac imaging.
3. Diffusing capacity of the lungs for carbon monoxide (DLCO) =65% or forced expiratory volume (FEV1) =65%.
4. Creatinine clearance =30 to <45 mL/min calculated by modification of diet in renal disease (MDRD) formula.
5. Moderate hepatic impairment with total bilirubin >1.5 to =3.0x upper limit of normal (ULN).
* Subject with an Eastern Cooperative Oncology Group (ECOG) performance status as follows:
a) 0 to 2 for participants =75 years of age or b) 0 to 3 for participants 18 to 74 years of age.
* For participants =75 years of age, adequate renal function demonstrated by a creatinine clearance =30 mL/min, calculated by modification of diet in renal disease (MDRD)
* Subject with adequate liver function demonstrated by the following:
1. For participants 18 to 74 years of age, aspartate aminotransferase (AST) =3.0 × ULN, alanine aminotransferase (ALT) =3.0 × ULN and bilirubin =3.0 × ULN, unless considered due to leukemic organ involvement ?5 × ULN.
2. For participants =75 years of age, aspartate aminotransferase (AST) =3.0 × ULN, alanine aminotransferase (ALT) =3.0 × ULN and bilirubin =1.5 × ULN, unless considered due to leukemic organ involvement ?5 × ULN.
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
* Any clinically significant, uncontrolled medical conditions (including any serious active systemic infection that is not controlled)
* Known second malignancy either progressing or requiring active treatment within the last 3 years prior to first IMP administration
* Known acquired immunodeficiency syndrome (AIDS-related illnesses) or HIV disease requiring antiretroviral treatment, or having active hepatitis B or C infection, or SARS-CoV-2 infection. With exception for:
1. HBV as determined by positive test for hepatitis B surface antigen (HBsAg) and/or HBV DNA. Participant who tests positive for anti-hepatitis B core (HBc) antigen IgG (with or without testing positive for anti-HBs), but tests negative for HBsAg and HBV DNA, is eligible.
2. A participant who tests positive for anti-HCV antibodies and has undetectable HCV RNA without receiving antiviral treatment for HCV is eligible.
* Active, known, or suspected clinically significant autoimmune disease that has required systemic treatment in the past 2 years prior to first IMP administration, except controlled by replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc)
* Predicted life expectancy =3 months.
* Medical conditions requiring treatment with medications with narrow therapeutic index that are substrates of CYP enzymes and that cannot be closely monitored to allow for dose adjustment.
* Ongoing adverse event of NCI CTCAE [Version 5.0] Grade 2 or greater severity cause by any prior anti-cancer therapy
Substudy 01:
* Patient with Acute Promyelocytic Leukemia (APL)
* Known active central nervous system involvement with AML at the time of enrollment as evidenced by cytology or pathology
* Cardiovascular disease of New York Heart Association (NYHA) Class =2.
* Malabsorption syndrome or other condition that precludes enteral route of administration
* A baseline QTc interval of (using the Fridericia correction calculation) >470 msec.
* Subject has received treatment with at least one of the following:
1. A hypomethylating agent, venetoclax and/or chemo therapeutic agent for AML other than hydroxyurea used for disease control prior to the initiation of study therapy.
2. Experimental therapies for AML.
3. Concomitant medications of strong and moderate CYP3A inducers within 7 days prior to the initiation of study treatment.
The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Not applicable
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Single group
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Other design features
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Phase
Phase 1
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Active, not recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
13/08/2024
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
2/06/2026
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Actual
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Sample size
Target
18
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Accrual to date
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Final
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Recruitment in Australia
Recruitment state(s)
NSW,VIC
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Recruitment hospital [1]
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Investigational Site Number : 0360002 - Wollongong
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Recruitment hospital [2]
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Investigational Site Number : 0360001 - Melbourne
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Recruitment postcode(s) [1]
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2500 - Wollongong
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Recruitment postcode(s) [2]
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3000 - Melbourne
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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California
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Country [2]
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United States of America
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State/province [2]
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New York
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Country [3]
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United States of America
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State/province [3]
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Ohio
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Country [4]
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United States of America
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State/province [4]
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Oregon
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Country [5]
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United States of America
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State/province [5]
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Texas
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
Sanofi
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Address
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Country
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Ethics approval
Ethics application status
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Summary
Brief summary
This is a parallel, Phase 1/Phase 2, randomized, open label, multi-cohort, multi-center study assessing the safety, tolerability and preliminary efficacy of SAR443579 with different agents for treatment in adolescent and/or adult participants with CD123 expressing hematological malignancies. This protocol is structured as a master protocol (containing common protocol elements). Individual sub-studies will explore SAR443579 with combination partners, which may include approved or investigational agents. Experimental sub-studies will be tested through 3 parts: Part 1: dose finding (such as dose escalation/ safety run-in). Part 2: dose optimization (when applicable). Part 3: dose expansion. In each sub-study, a dose escalation will identify preliminary recommended dose for expansion (pRDE) of SAR443579 and its respective combination partner. Following the determination of the preliminary RDE, additional participants will be enrolled in the dose expansion part, or if dose optimization needs to be further evaluated, additional participants will be enrolled in the "dose optimization/expansion" part. Dose optimization and dose expansion part could involve randomization depending on specific sub-study design. Study will consist of a screening period, treatment period, and follow-up period. Participants will receive study treatment until documented disease progression, unacceptable adverse events, participant's decision to stop study treatment, or completion of the maximum cycles allowed in the sub-studies, or the participant meets other criteria for discontinuation per study protocol (whichever occurs first).
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Trial website
https://clinicaltrials.gov/study/NCT06508489
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Address
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Trial Transparency email recommended (Toll free for US & Canada)
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Address
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Country
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Phone
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800-633-1610
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Fax
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Email
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[email protected]
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Contact person for scientific queries
Data sharing statement
What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT06508489
Download to PDF