A Study to Investigate Use of Off-the-shelf Natural Killer (NK) Cells (SAR445419) in Relapsed/Refractory Acute Myeloid Leukemia
- Conditions
- Acute Myeloid Leukaemia
- Interventions
- Registration Number
- NCT05712278
- Lead Sponsor
- Sanofi
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 7
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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description SAR445419 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. SAR445419 fludarabine 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. SAR445419 cytarabine 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.
- Primary Outcome Measures
Name Time Method Incidence of DLT from start of chemotherapy From Day -6 to Day 28 Incidence of dose-limiting (DLT) toxicity from Day 1 to Day 28
- Secondary Outcome Measures
Name Time Method Number of participants with adverse events (AEs) From baseline up to 1 year Median time to neutrophil and platelet count recovery From Day -6 up to 1 year Median time to neutrophil and platelet count recovery post chemotherapy
Rate of HSCT 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
Percentage of participants with Composite Complete Remission (CRc) rate 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
Percentage of participants with overall complete remission rate From baseline up to Day 56 Percentage of participants with CR or CRh or CRi or morphological leukemia-free state (MLFS)
Number of participants with infection From baseline up to 1 year Percentage of participants with alternative complete remission rate From baseline up to Day 56 Percentage of participants with CR or a complete remission with partial hematological recovery (CRh)
Number of participants by type of infection From baseline up to 1 year Fungal, bacterial, viral, and particularly cytomegalovirus (CMV) infection or reactivation (opportunistic) infection
Duration of response 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
Duration of event-free survival 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
Overall survival rate at 6 months From baseline up to 6 months Time from the first SAR445419 administration to death from any cause
Overall survival rate at 1 year From baseline up to 1 year Time from the first SAR445419 administration to death from any cause
Time to treatment failure From baseline up to 1 year Time from first SAR445419 administration to discontinuation for any reason excluding remission
Trial Locations
- Locations (3)
~MD Anderson Cancer Center Site Number : 8400002
🇺🇸Houston, Texas, United States
University of Nebraska Medical Center Site Number : 8400003
🇺🇸Omaha, Nebraska, United States
Albert Einstein College of Medicine Site Number : 8400001
🇺🇸Bronx, New York, United States