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)

NCT ID: NCT05086315

Last Updated: 2025-12-15

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 101 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-08
• Study Completion Date: 2025-06-13

Brief Summary

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.

Detailed Description

Study duration per participant is 2.5 years.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

SAR443579

Intervention Type: DRUG

Powder for solution for infusion; by IV infusion

Interventions

SAR443579

Powder for solution for infusion; by IV infusion

Intervention Type: DRUG

Eligibility Criteria

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.

The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.

• Minimum Eligible Age: 1 Year
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

City of Hope-Site Number:8400002

Duarte, California, United States

Emory University School of Medicine- Grady Campus- Site Number : 8400006

Atlanta, Georgia, United States

Beth Israel Deaconess Medical Center-Site Number:8400004

Boston, Massachusetts, United States

Weill Cornell Medical College-Site Number:8400003

New York, New York, United States

Montefiore Hutchinson Campus- Site Number : 8400012

The Bronx, New York, United States

The Ohio State University- Site Number : 8400009

Columbus, Ohio, United States

Oregon Health and Science University-Site Number:8400011

Portland, Oregon, United States

The Children's Hospital of Philadelphia- Site Number : 8400013

Philadelphia, Pennsylvania, United States

MD Anderson Cancer Center-Site Number:8400001

Houston, Texas, United States

Seattle Children's Hospital- Site Number : 8400014

Seattle, Washington, United States

Investigational Site Number :0360002

Melbourne, Victoria, Australia

Investigational Site Number :0360001

Melbourne, Victoria, Australia

Investigational Site Number : 1560001

Tianjin, , China

Investigational Site Number : 1560003

Zhengzhou, , China

Investigational Site Number :2500002

Marseille, , France

Investigational Site Number :2500001

Paris, , France

Investigational Site Number : 2500004

Paris, , France

Investigational Site Number :2500003

Villejuif, , France

Investigational Site Number :5280002

Amsterdam, , Netherlands

Investigational Site Number :5280003

Groningen, , Netherlands

Investigational Site Number : 5280005

Nijmegen, , Netherlands

Investigational Site Number :5280001

Rotterdam, , Netherlands

Investigational Site Number :5280004

Utrecht, , Netherlands

Countries

United States; Australia; China; France; Netherlands

Related Links

https://sanofi.trialsummaries.com/Study/StudyDetails?id=25348&tenant=MT_SNY_9011

TCD17197 Plain Language Results Summary

Other Identifiers

U1111-1266-7399

Identifier Type: REGISTRY

Identifier Source: secondary_id

2023-508357-58

Identifier Type: REGISTRY

Identifier Source: secondary_id

2021-004287-98

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

TCD17197

Identifier Type: -

Identifier Source: org_study_id