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

Acute Myeloid Leukaemia Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05712278
• Other study ID #: TED17749
• Secondary ID: U1111-1279-2948
• Status: Terminated
• Phase: Phase 1
• Start date: June 16, 2023
• Est. completion date: March 12, 2024

Study information

• Verified date: April 2024
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: March 12, 2024
• Est. primary completion date: February 23, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Myeloid Leukaemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• SAR445419
Cell suspension, by intraveneous (IV) injection
• fludarabine
Solution for injection , by IV injection
• cytarabine
Solution for injection, by IV injection

Locations

Country	Name	City	State
United States	Albert Einstein College of Medicine Site Number : 8400001	Bronx	New York
United States	~MD Anderson Cancer Center Site Number : 8400002	Houston	Texas
United States	University of Nebraska Medical Center Site Number : 8400003	Omaha	Nebraska

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of dose-limiting (DLT) toxicity		from Day 1 to Day 28
Primary	Incidence of DLT from start of chemotherapy		From Day -6 to Day 28
Secondary	Number of participants with adverse events (AEs)		From baseline up to 1 year
Secondary	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
Secondary	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
Secondary	Number of participants with infection		From baseline up to 1 year
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Overall survival rate at 6 months	Time from the first SAR445419 administration to death from any cause	From baseline up to 6 months
Secondary	Overall survival rate at 1 year	Time from the first SAR445419 administration to death from any cause	From baseline up to 1 year
Secondary	Time to treatment failure	Time from first SAR445419 administration to discontinuation for any reason excluding remission	From baseline up to 1 year