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

• ClinicalTrials.gov Identifier: NCT05712278
• Recruitment Status: Terminated
• First Posted: February 3, 2023
• Last Update Posted: April 12, 2024
• Sponsor: Sanofi
• Information provided by (Responsible Party): Sanofi

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Acute Myeloid Leukaemia	Drug: SAR445419; Drug: fludarabine; Drug: cytarabine	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 7 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: June 16, 2023
• Actual Primary Completion Date: February 23, 2024
• Actual Study Completion Date: March 12, 2024

Arms and Interventions

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 Name: fludara; Drug: cytarabine; Solution for injection, by IV injection; Other Name: cytosar-U

Outcome Measures

Primary Outcome Measures :

1. Incidence of dose-limiting (DLT) toxicity [ Time Frame: from Day 1 to Day 28 ]
2. Incidence of DLT from start of chemotherapy [ Time Frame: From Day -6 to Day 28 ]

Secondary Outcome Measures :

1. Number of participants with adverse events (AEs) [ Time Frame: From baseline up to 1 year ]
2. Median time to neutrophil and platelet count recovery [ Time Frame: From Day -6 up to 1 year ]
   Median time to neutrophil and platelet count recovery post chemotherapy
3. Rate of HSCT [ Time Frame: From baseline up to 1 year ]
   Percentage of participants going onto hematopoietic stem cell transplantation (HSCT) following SAR445419 treatment but prior to subsequent therapy for treatment of AML
4. Number of participants with infection [ Time Frame: From baseline up to 1 year ]
5. Number of participants by type of infection [ Time Frame: From baseline up to 1 year ]
   Fungal, bacterial, viral, and particularly cytomegalovirus (CMV) infection or reactivation (opportunistic) infection
6. Percentage of participants with Composite Complete Remission (CRc) rate [ Time Frame: From baseline up to Day 56 ]
   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
7. Percentage of participants with alternative complete remission rate [ Time Frame: From baseline up to Day 56 ]
   Percentage of participants with CR or a complete remission with partial hematological recovery (CRh)
8. Percentage of participants with overall complete remission rate [ Time Frame: From baseline up to Day 56 ]
   Percentage of participants with CR or CRh or CRi or morphological leukemia-free state (MLFS)
9. Duration of response [ Time Frame: From baseline up to 1 year ]
   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
10. Duration of event-free survival [ Time Frame: From baseline up to 1 year ]
    Time interval from date of first SAR445419 administration to induction failure, relapse or death due to any cause, whichever comes first
11. Overall survival rate at 6 months [ Time Frame: From baseline up to 6 months ]
    Time from the first SAR445419 administration to death from any cause
12. Overall survival rate at 1 year [ Time Frame: From baseline up to 1 year ]
    Time from the first SAR445419 administration to death from any cause
13. Time to treatment failure [ Time Frame: From baseline up to 1 year ]
    Time from first SAR445419 administration to discontinuation for any reason excluding remission

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Nebraska

University of Nebraska Medical Center Site Number : 8400003

Omaha, Nebraska, United States, 68198-2168

United States, New York

Albert Einstein College of Medicine Site Number : 8400001

Bronx, New York, United States, 10461

United States, Texas

~MD Anderson Cancer Center Site Number : 8400002

Houston, Texas, United States, 77030

Sponsors and Collaborators

Sanofi

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

More Information

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT05712278
• Other Study ID Numbers: TED17749; U1111-1279-2948 ( Other Identifier: ICTRP )
• First Posted: February 3, 2023
• Last Update Posted: April 12, 2024
• Last Verified: April 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Cytarabine; Fludarabine; Antineoplastic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antiviral Agents; Anti-Infective Agents