TERMINATED

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)

Conditions

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

An Open-label, First-in-human, Dose-escalation/Expansion Study of SAR443579 Administered as Single Agent by Intravenous Infusion in Adult and Pediatric 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)

Quick Facts

Study Start:2021-12-08

Study Completion:2025-05-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:TERMINATED

Study ID

NCT05086315

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:1 Year

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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. 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	* 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.

Inclusion Criteria

Exclusion 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.
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

* 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.

Contacts and Locations

Principal Investigator

Clinical Sciences & Operations

STUDY_DIRECTOR

Sanofi

Study Locations (Sites)

City of Hope-Site Number:8400002

Duarte, California, 91010

United States

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

Atlanta, Georgia, 30303

United States

Beth Israel Deaconess Medical Center-Site Number:8400004

Boston, Massachusetts, 02215

United States

Montefiore Hutchinson Campus- Site Number : 8400012

Bronx, New York, 10461

United States

Weill Cornell Medical College-Site Number:8400003

New York, New York, 10021

United States

The Ohio State University- Site Number : 8400009

Columbus, Ohio, 43210

United States

Oregon Health and Science University-Site Number:8400011

Portland, Oregon, 97239

United States

Children's Hospital of Philadelphia-3401 Civic Center Blvd Site Number : 8400013

Philadelphia, Pennsylvania, 19104-4318

United States

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

Philadelphia, Pennsylvania, 19104

United States

MD Anderson Cancer Center-Site Number:8400001

Houston, Texas, 77030

United States

Seattle Children's Hospital- Site Number : 8400014

Seattle, Washington, 98105

United States

Collaborators and Investigators

Sponsor: Sanofi

Clinical Sciences & Operations, STUDY_DIRECTOR, Sanofi

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-12-08

Study Completion Date2025-05-12

Study Record Updates

Study Start Date2021-12-08

Study Completion Date2025-05-12

Terms related to this study

Additional Relevant MeSH Terms

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