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)
Overview
- Phase
- Phase 1
- Intervention
- SAR445419
- Conditions
- Acute Myeloid Leukaemia
- Sponsor
- Sanofi
- Enrollment
- 7
- Locations
- 3
- Primary Endpoint
- Incidence of DLT from start of chemotherapy
- Status
- Terminated
- Last Updated
- 7 months ago
Overview
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.
Investigators
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.
Arms & Interventions
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.
Intervention: 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.
Intervention: fludarabine
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.
Intervention: cytarabine
Outcomes
Primary Outcomes
Incidence of DLT from start of chemotherapy
Time Frame: From Day -6 to Day 28
Incidence of dose-limiting (DLT) toxicity
Time Frame: from Day 1 to Day 28
Secondary Outcomes
- 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)
- Rate of HSCT(From baseline up to 1 year)
- Percentage of participants with Composite Complete Remission (CRc) rate(From baseline up to Day 56)
- Percentage of participants with overall complete remission rate(From baseline up to Day 56)
- 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)
- Number of participants by type of infection(From baseline up to 1 year)
- Duration of response(From baseline up to 1 year)
- Duration of event-free survival(From baseline up to 1 year)
- Overall survival rate at 6 months(From baseline up to 6 months)
- Overall survival rate at 1 year(From baseline up to 1 year)
- Time to treatment failure(From baseline up to 1 year)