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First-in-human Study of SAR443579 Infusion in Male and Female Children and Adult Participants With Relapsed or Refractory Acute Myeloid Leukemia (R/R AML), B-cell Acute Lymphoblastic Leukemia (B-ALL), High Risk-myelodysplasia (HR-MDS), or Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

PHASE1PHASE2RECRUITING

This is an open-label, multicenter, Phase 1/Phase 2, dose escalation and dose expansion study to evaluate the safety, pharmacokinetics, pharmacodynamics and anti-leukemic activity of SAR443579 in various hematological malignancies.

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Study details:

Study duration per participant is 2. 5 years.

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Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

  • Participant must be at least 1 year (for France: 2 years) old at the time the trial participant or legal guardian signs the informed consent form and will be assigned as follows: Adult arm: aged at least 18 years old. Pediatric arm: aged 1 (for France: 2 years) to less than 18 years old.
  • Adult and Pediatric Arms: Escalation and Expansion/Optimization Cohorts A1, A2, C, D: Confirmed diagnosis of primary or secondary AML (any subtype) according to World Health Organization (WHO) 2022 classification. Participants with AML must meet one of the following criteria, a), b), c) or d) and are limited to those with no available (or are ineligible) therapy with known clinical benefit.
  • a) Primary Induction Failure (PIF) AML, defined as disease refractory to one of the following, i or ii. i) An intensive induction attempt, per institution. Induction attempts include high-dose and/or standard-dose cytarabine ± an anthracyclines/anthracenedione ± an anti-metabolite, with or without growth factor or targeted therapy containing regimens. ii) For adults who are age 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy; PIF is defined as AML refractory to one of the following less intensive regimens, 1 or 2: 1. 4 cycles of hypomethylating agents (HMA) or 2. 2 cycles HMA + venetoclax b) Early relapse (ER) AML, defined as AML in relapse with CR, CRh or CRi duration less than 6 months on prior induction treatment c) Leukemia in first or higher relapse d) For participants aged 1 (for France: 2 years) to less than 18 years old, primary induction failure is defined as disease refractory after two cycles of induction therapy.
  • Adult Arm (Escalation and Expansion/Optimization Cohorts B and Japan Cohort C only): Confirmed diagnosis of MDS, meeting the following criteria: 1. intermediate or high-risk category as per a Revised International Prognostic Scoring System (IPSS-R) AND 2. confirmed CD123 + expression status determined by local institutional standards AND 3. limited to those with no available (or are ineligible) therapy with known clinical benefit.
  • Pediatric arms escalation part and Japan Cohort C only: Confirmed diagnosis of CD123+ BALL without extramedullary lesions that have no available (or are ineligible) therapy with known clinical benefit. Participants with non-CNS chloromatous disease are not allowed in the study.
  • Body weight at least 10 kg.
  • Pediatric arm and escalation part only: Confirmed diagnosis of BPDCN according to World Health Organization (WHO) 2022 classification, who have relapsed or refractory disease with no available (or are ineligible) therapy with known clinical benefit.
  • Japan participants (Cohort C): Participant must be at least 18 years old at the time the trial participant signs the informed consent form
  • Exclusion criteria

  • Eastern Cooperative Oncology Group (ECOG) performance status greater than 2 (at least 18 years-old). Karnofsky Scale (16 to 17 years-old) less than 50% or Lansky Scale (less than 16 years-old) less than 50%.
  • Ongoing or recent (within 5 years) evidence of significant autoimmune disease that requires or required treatment with systemic immunosuppressive treatments, which may suggest a risk for immune-related adverse events. The following are not exclusionary: vitiligo, childhood asthma that has resolved, residual hypothyroidism that required only hormone replacement or psoriasis that does not require systemic treatment.
  • History of an invasive malignancy within the last 3 years prior to first IMP administration that requires active therapy (adjuvant hormonal therapy is allowed) other than the one treated in this study.
  • Evidence of active central nervous system leukemia at the time of enrollment as evidenced by cytology or pathology. Except for participants aged 1 (for France: 2 years) to less than 18 years, central nervous system 1 disease (CNS1) and CNS2 disease are allowed.
  • Known acquired immunodeficiency syndrome (AIDS-related illnesses) or human immunodeficiency virus (HIV) disease requiring antiretroviral treatment, or having active hepatitis B or C infection, or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
  • Prior treatment with an anti-CD123-directed agent (except for participants with BPDCN in the pediatric arm).
  • Prior HSCT with relapse beyond 3 months or prior CAR-T therapy in B-ALL with relapse beyond 2 months may be included only if off immunosuppression for a minimum of 4 weeks and no evidence of GVHD.
  • Receiving at the time of first investigational medicinal product (IMP) administration corticosteroid as a concomitant medication with corticosteroid dose more than 10 mg/day of oral prednisone or the equivalent.
  • AML, BPDCN, or HR-MDS participants with prior treatment with cellular therapy, eg, chimeric antigen receptor T cell (CAR-T) or chimeric antigen receptor NK cell (CAR-NK). Prior CAR-T therapy is allowed for participants with B-ALL.
  • Concurrent treatment with other investigational drugs.
  • Pregnant and breast-feeding women.
  • History of solid organ transplant, including corneal transplant.
  • Average QTc (using the Fridericia correction calculation) greater than 470 millisecond (msec) at screening.
  • Pediatric arm only: Participants with known inherited bone marrow failure syndromes (e.g., bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Shwachman syndrome). Participants with Down syndrome with adequate organ function as per Investigator discretion are allowed to participate in the study.
  • Adult arm Expansion/Optimization- Participants with MDS evolving from a pre-existing myeloproliferative neoplasm (MPN), MDS/MPN including chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia (aCML), unclassifiable MDS/MPN and therapy-related MDS (t-MDS).
  • Confirmed diagnosis of acute promyelocytic leukemia (APL) or juvenile myelomonocytic leukemia (JMML) according to WHO 2022 classification.
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    Eligibility

    Age eligible for study : 1 and older

    Healthy volunteers accepted : No

    Gender eligible for study: All

    Things to know

    Study dates

    Study start: 2021-12-08

    Primary completion: 2025-12-11

    Study completion finish: 2030-10-15

    study type

    Study type

    TREATMENT

    phase

    Phase

      PHASE1

      PHASE2

    trial

    Trial ID

    NCT05086315

    Intervention or treatment

    DRUG: SAR443579

    Conditions

    • Myelodysplastic Syndromes
    • Acute Lymphocytic Leukaemia
    • Acute Myeloid Leukaemia Refractory
    • Blastic Plasmacytoid Dendritic Cell Neoplasia

    Find a site

    Closest Location:

    Investigational Site Number :0360002

    Research sites nearby

    Select from list below to view details:

    • Investigational Site Number :0360002

      Melbourne, Victoria, Australia

    • Investigational Site Number :0360001

      Melbourne, Victoria, Australia

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    Study Plan

    This section provides details of the study plan, including how the study is designed and what the study is measuring.

    How is the study designed?

    Participant Group/ArmIntervention/Treatment
    EXPERIMENTAL: SAR443579
    • Dose Escalation: SAR443579 administered intravenously at escalating dose levels.
    • Dose Expansion: SAR443579 administered intravenously at the recommended dose and schedule determined from the dose escalation.
    DRUG: SAR443579
    • Powder for solution for infusion; by IV infusion

    What is the study measuring?

    Primary outcome

    Primary Outcome MeasurePrimary Outcome DescriptionPrimary Outcome Time Frame
    Escalation Part: Incidence of dose-limiting toxicity (DLT)DLTs encompass both hematologic and nonhematologic toxicities, prespecified adverse reactions observed post-administration of SAR443579 and assessed by both the investigator and the sponsor.Day 1 to Day 28
    Japan Cohort C: Incidence of DLT in Japanese participantsDLTs encompass both hematologic and nonhematologic toxicities, prespecified adverse reactions observed post-administration of SAR443579 and assessed by both the investigator and the sponsor.Day 1 to Day 28
    Expansion/Optimization part (Cohorts A1, A2 & D), AML: Proportion of participants who have a CR + CRh + CRi according to the modified AML IWG 2003 criteriaMeasure of clinical response to treatment: Proportion of participants who have a complete remission (CR) + CR with partial hematologic recovery (CRh) + CR with incomplete hematologic recovery (CRi) according to the modified acute myeloid leukemia (AML) IWG 2003 criteria.Up to 6 months
    Expansion/Optimization part (Cohort B), MDS: Overall response rate (CR + CR equivalent + PR + CRL + CRh + HI) according to the IWG 2023 MDS response criteriaMeasure of clinical response to treatment: Overall response rate (CR + CR equivalent + partial remission (PR) + CR with limited count recovery (CRL) + CRh + hematologic improvement (HI)) according to the International Working Group (IWG) 2023 myelodysplasia (MDS) response criteria.Up to 6 months

    Secondary outcome

    Secondary Outcome MeasureSecondary Outcome DescriptionSecondary Outcome Time Frame
    Expansion/Optimization part - Cohorts A, B and D: Recommended dose for expansion (RDE)Recommended dose for expansion (RDE) of SAR443579.Up to 12 months
    Escalation and Expansion/Optimization parts - Cohorts A, B, C and D: Number of participants with TEAEsNumber of participants with treatment-emergent adverse events (TEAEs).Up to 30 months
    Escalation and Expansion/Optimization parts - Cohorts A, B, C and D: CtroughConcentration observed just before treatment administration during repeated dosing (Ctrough).Day 1 to end of trial (maximum up to 30 months)
    Escalation and Expansion/Optimization parts - Cohorts A, B, C and D: Incidence of ADAPercentage of participants with anti-drug antibody (ADA).Up to 30 months
    Escalation and Expansion/Optimization parts - Japan Cohort C, AML: Rate of CR + CRh + CRi per AML 2003 modified IWG response criteriaMeasure of clinical response to treatment.Up to 6 months
    Escalation and expansion/Optimization parts - Japan Cohort C, MDS: CR rate and ORR rate per IWG 2023 MDS response criteria for escalation part and ORR rate per IWG 2023Measure of clinical response to treatment.Up to 6 months
    Escalation and Expansion/Optimization parts - Japan Cohort C, B-ALL: Rate of CR + CRh + CRi as defined by National Comprehensive Cancer Network (NCCN)Measure of clinical response to treatment.Up to 6 months
    Expansion/Optimization part - Cohorts A and D: Overall response rate (ORR)Measure of clinical response to treatment.Up to 6 months
    Expansion/Optimization part - Cohorts A and D: Duration of CR + CRh + CRi (Duration of CRc)Measure the length of clinical response to treatment.Up to 30 months
    Expansion/Optimization part - Cohorts A and D: Duration of CR + CRi + CRh + PR + MLFS (Duration of overall response rate)Measure the length of clinical response to treatment.Up to 30 months
    Expansion/Optimization part - Cohorts A and D: Alternative CR rateMeasure of clinical response to treatment.Up to 6 months
    Expansion/Optimization part - Cohorts A and D: Duration of CR + CRh (Duration of alternative CR)Measure the length of clinical response to treatment.Up to 30 months
    Expansion/Optimization part - Cohorts A and D: Event-free survival (EFS)EFS is defined as the time interval from the first day of treatment assignment to the date of earliest evidence of relapse, treatment failure, or death.Up to 6 months
    Expansion/Optimization part - Cohorts A and D: Overall survival (OS)OS is defined as time interval from the first day of treatment assignment to death from any cause.Up to 30 months
    Expansion/Optimization part - Cohorts A and D: Rate of hematopoietic stem cell transplantation (HSCT)Rate of HSCT procedures immediately following study treatment administration but prior to subsequent therapy for treatment of AML.Up to 30 months
    Expansion/Optimization part - Cohorts A and D: Time to treatment failure (TTF)TTF is defined as the time from first day of treatment assignment to discontinuation for any reason excluding remission, eg, relapsed disease, refractory disease, unacceptable AE, participant preference or death.Up to 6 months
    Expansion/Optimization part - Cohorts A and D: Rate of conversion from transfusion dependenceRate of conversion from transfusion dependence during 56-day post-baseline period.Day 0 to Day 56
    Expansion/Optimization part - Cohorts A and D: Rate of participants who are transfusion independent at baseline and remain independent during 56-day postbaseline periodRate of participants who are transfusion independent at baseline and remain independent during 56-day postbaseline period.Day 0 to Day 56
    Expansion/Optimization part - Cohort B: Alternative CR rateAlternative CR rate defined as proportion of participants with CR, CR equivalent, CRuni, CRbi, and CRh.Up to 6 months
    Expansion/Optimization part - Cohort B: Duration of ORRThe time interval from the first documented evidence of CR, CR equivalent, CRL, CRh, PR or HI to PD or relapse from CR, CR equivalent, CRL, CRh, PR or HI as per 2023 IWG recommendations or death due to any cause, whichever comes first.Up to 30 months
    Expansion/Optimization part - Cohort B: Event-free survival (EFS)EFS is defined as the time interval from the first day of treatment assignment to the date of protocol specified events.Up to 30 months
    Expansion/Optimization part - Cohort B: Overall survival (OS)OS is defined as time interval from the first day of treatment assignment to death from any cause.Up to 30 months
    Expansion/Optimization part - Cohort B: Rate of hematopoietic stem cell transplantation (HSCT)Rate of HSCT procedures immediately following study treatment administration but prior to subsequent therapy.Up to 30 months
    Expansion/Optimization part - Cohort B: Time to treatment failure (TTF)TTF is defined as the time interval from first day of treatment assignment to discontinuation for any reason excluding remission, eg, relapsed disease, disease progression, unacceptable AE, participant preference or death.Up to 30 months
    Expansion/Optimization part - Cohort B: Duration of alternative CR (CR + CR equivalent + CRL + CRh)Measure the length of clinical response to treatment.Up to 30 months
    Expansion/Optimization part - Cohort B: Progression free survival (PFS)The time interval from the first day of treatment assignment to the date of PD, relapse from CR (or CR equivalent), PR, CRL, CRh, or HI, death due to any cause, whichever comes first.Up to 30 months

    Frequently Asked Questions

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    References

    Clinical Trials Gov: First-in-human Study of SAR443579 Infusion in Male and Female Children and Adult Participants With Relapsed or Refractory Acute Myeloid Leukemia (R/R AML), B-cell Acute Lymphoblastic Leukemia (B-ALL), High Risk-myelodysplasia (HR-MDS), or Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

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