A Study to Investigate Use of Off-the-shelf Natural Killer (NK) Cells (SAR445419) in Relapsed/Refractory Acute Myeloid Leukemia
Study Details
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:
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Screening period up to 21 days prior to initiating chemotherapy,
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Treatment period of 5 days chemotherapy followed by SAR445419 administered for 2 weeks and end of treatment visit 56 days after first SAR445419 administration,
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Survival follow-up period up to 1 year after the last participant has started treatment with SAR445419.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| 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
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 Names:
Drug: cytarabine
Solution for injection, by IV injection
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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
- Number of participants with infection [From baseline up to 1 year]
- 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
- 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 international working group (IWG) for AML
- 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)
- 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)
- Duration of response [From baseline up to 1 year]
Time interval from first documented evidence of CR until progressive disease (PD) as per modified IWG 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
Eligibility Criteria
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:
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Participants with relapsed AML after allogeneic stem cells transplantation, including those who have received donor lymphocyte infusions,
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Isolated central nervous system (CNS) or extramedullary disease,
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At least 1 prior line of therapy which includes chemotherapy, hypomethylating agents, venetoclax or targeted therapy.
Participants with a weight ≥42 kg.
Exclusion Criteria:
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Second primary malignancy that requires active therapy. Adjuvant hormonal therapy is allowed.
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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.
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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.
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History of solid organ transplant, including corneal transplant.
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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
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Known contraindication to any of the non-investigational medicinal products (NIMPs) (fludarabine, cytarabine, acetaminophen and diphenhydramine).
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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
No locations specified.Sponsors and Collaborators
- Sanofi
Investigators
- Study Director: Clinical Sciences & Operations, Sanofi
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- TED17749
- U1111-1279-2948