A Study to Investigate Use of Off-the-shelf Natural Killer (NK) Cells (SAR445419) in Relapsed/Refractory Acute Myeloid Leukemia

A Phase I, Single-arm, Open Label, Dose Escalation, Multicenter Study of Off-the-shelf Natural Killer (NK) Cells (SAR445419) in Participants With Relapsed or Refractory Acute Myeloid Leukemia (R/R AML)

This is a single group, Phase 1, single-arm, dose escalation study to determine the candidate dose(s), and evaluate safety, tolerability, and preliminary anti-tumor activity of SAR445419 administered after fludarabine and cytarabine conditioning for the treatment of relapsed or refractory acute myeloid leukemia (R/R AML). Adult participants with R/R AML will be eligible for treatment.

The study is intended to assess the candidate dose(s) by the occurrence of dose-limiting toxicity (DLT) from start of chemotherapy until 28 days after the first administration of SAR445419.

The duration of the study for a participant will include:

• Screening period up to 21 days prior to initiating chemotherapy,
• Treatment period of 5 days chemotherapy followed by SAR445419 administered for 2 weeks and end of treatment visit 56 days after first SAR445419 administration,
• Survival follow-up period up to 1 year after the last participant has started treatment with SAR445419.

Study Overview

• Status: Terminated
• Conditions: Acute Myeloid Leukaemia
• Intervention / Treatment: Drug: SAR445419; Drug: fludarabine; Drug: cytarabine

Detailed Description

Participants will be followed for 28 days (for DLT evaluations) after administration of the first SAR445419 dose (Day 1) for the primary endpoint and for 1 year after the first SAR445419 dose for selected secondary endpoints.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Trial Transparency email recommended (Toll free for US & Canada); Phone Number: option 6 800-633-1610; Email: contact-us@sanofi.com

Study Locations

• United States
  • Nebraska
    • Omaha, Nebraska, United States, 68198-2168
      • University of Nebraska Medical Center Site Number : 8400003
  • New York
    • Bronx, New York, United States, 10461
      • Albert Einstein College of Medicine Site Number : 8400001
  • Texas
    • Houston, Texas, United States, 77030
      • ~MD Anderson Cancer Center Site Number : 8400002

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Participant must be 18 years of age inclusive

Participants with confirmed diagnosis of relapsed or primary refractory acute myeloid leukemia (AML), according to World Health Organization (WHO) classification, including:

• Participants with relapsed AML after allogeneic stem cells transplantation, including those who have received donor lymphocyte infusions,
• Isolated central nervous system (CNS) or extramedullary disease,
• At least 1 prior line of therapy which includes chemotherapy, hypomethylating agents, venetoclax or targeted therapy.

Participants with a weight ≥42 kg.

Exclusion Criteria:

• Second primary malignancy that requires active therapy. Adjuvant hormonal therapy is 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 symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
• Pregnant or breast-feeding women, female participants of childbearing potential, and male participants with female partners of childbearing potential who are not willing to avoid pregnancy by using a highly effective method of contraception (2 barrier method or 1 barrier method with a spermicide, intrauterine device, or hormonal contraception with inhibition of ovulation, for 2 weeks prior to the first dose of SAR445419, during treatment, and 6 months after the last dose of fludarabine). A woman is considered of childbearing potential, i.e., fertile, following menarche and until becoming postmenopausal unless permanently sterile.
• History of solid organ transplant, including corneal transplant.
• Receiving at the time of first SAR445419 administration corticosteroid as a concomitant medication with corticosteroid dose >10 mg/day of oral prednisone or the equivalent, except steroid inhaler, nasal spray, or ophthalmic solution
• Known contraindication to any of the non-investigational medicinal products (NIMPs) (fludarabine, cytarabine, acetaminophen and diphenhydramine).
• Concurrent treatment with other investigational drugs

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SAR445419; Treatment consists of chemotherapy with fludarabine 30mg/m2/day and cytarabine 2g/m2/day administered for 5 days (Day -6 to Day -2), followed by 6 doses of SAR445419 given thrice weekly for 2 weeks beginning Day 1.	Drug: SAR445419; Cell suspension, by intraveneous (IV) injection; Drug: fludarabine; Solution for injection , by IV injection; Other Names: fludara; Drug: cytarabine; Solution for injection, by IV injection; Other Names: cytosar-U

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of dose-limiting (DLT) toxicity	from Day 1 to Day 28
Incidence of DLT from start of chemotherapy	From Day -6 to Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events (AEs)		From baseline up to 1 year
Rate of HSCT	Percentage of participants going onto hematopoietic stem cell transplantation (HSCT) following SAR445419 treatment but prior to subsequent therapy for treatment of AML	From baseline up to 1 year
Number of participants with infection		From baseline up to 1 year
Number of participants by type of infection	Fungal, bacterial, viral, and particularly cytomegalovirus (CMV) infection or reactivation (opportunistic) infection	From baseline up to 1 year
Percentage of participants with alternative complete remission rate	Percentage of participants with CR or a complete remission with partial hematological recovery (CRh)	From baseline up to Day 56
Percentage of participants with overall complete remission rate	Percentage of participants with CR or CRh or CRi or morphological leukemia-free state (MLFS)	From baseline up to Day 56
Duration of event-free survival	Time interval from date of first SAR445419 administration to induction failure, relapse or death due to any cause, whichever comes first	From baseline up to 1 year
Overall survival rate at 6 months	Time from the first SAR445419 administration to death from any cause	From baseline up to 6 months
Overall survival rate at 1 year	Time from the first SAR445419 administration to death from any cause	From baseline up to 1 year
Time to treatment failure	Time from first SAR445419 administration to discontinuation for any reason excluding remission	From baseline up to 1 year
Median time to neutrophil and platelet count recovery	Median time to neutrophil and platelet count recovery post chemotherapy	From Day -6 up to 1 year
Percentage of participants with Composite Complete Remission (CRc) rate	Percentage of participants who have a complete remission (CR) or a complete remission with incomplete hematological recovery (CRi) as defined by the modified European LeukemiaNet (ELN) 2022 criteria for AML	From baseline up to Day 56
Duration of response	Time interval from first documented evidence of CR until progressive disease (PD) as per modified ELN 2022 criteria for AML or death due to any cause, whichever comes first	From baseline up to 1 year

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): June 16, 2023
• Primary Completion (Actual): February 23, 2024
• Study Completion (Actual): March 12, 2024

Study Registration Dates

• First Submitted: January 26, 2023
• First Submitted That Met QC Criteria: February 2, 2023
• First Posted (Actual): February 3, 2023

Study Record Updates

• Last Update Posted (Actual): April 12, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Fludarabine; Cytarabine
• Other Study ID Numbers: TED17749; U1111-1279-2948 (Other Identifier: ICTRP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No