Clinical trial NCT05712278: A Study to Investigate Use of Off-the-shelf Natural Killer (NK) Cells (SAR445419) in Relapsed/Refractory Acute Myeloid Leukemia
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Acute Myeloid Leukaemia
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2023-02-03
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Incidence of dose-limiting (DLT) toxicity
timeFrame: from Day 1 to Day 28
measure: Incidence of DLT from start of chemotherapy
timeFrame: From Day -6 to Day 28
Secondary outcomes:
measure: Number of participants with adverse events (AEs)
timeFrame: From baseline up to 1 year
measure: Median time to neutrophil and platelet count recovery
timeFrame: From Day -6 up to 1 year
measure: Rate of HSCT
timeFrame: From baseline up to 1 year
measure: Number of participants with infection
timeFrame: From baseline up to 1 year
measure: Number of participants by type of infection
timeFrame: From baseline up to 1 year
measure: Percentage of participants with Composite Complete Remission (CRc) rate
timeFrame: From baseline up to Day 56
measure: Percentage of participants with alternative complete remission rate
timeFrame: From baseline up to Day 56
measure: Percentage of participants with overall complete remission rate
timeFrame: From baseline up to Day 56
measure: Duration of response
timeFrame: From baseline up to 1 year
measure: Duration of event-free survival
timeFrame: From baseline up to 1 year
measure: Overall survival rate at 6 months
timeFrame: From baseline up to 6 months
measure: Overall survival rate at 1 year
timeFrame: From baseline up to 1 year
measure: Time to treatment failure
timeFrame: From baseline up to 1 year
Other outcomes:
Locations:
city: Omaha
country: United States
facility: University of Nebraska Medical Center Site Number : 8400003
state: Nebraska
city: Bronx
country: United States
facility: Albert Einstein College of Medicine Site Number : 8400001
state: New York
city: Houston
country: United States
facility: ~MD Anderson Cancer Center Site Number : 8400002
state: Texas
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: