Participants with high risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) undergoing allogeneic HSCT will receive 3 doses of SAR445419. A myeloablative conditioning (MAC) and a reduced intensity conditioning (RIC) cohort will be included.

Pharmaceutical form: cell suspension Route of administration: Intravenous (IV) injection

SAR445419

Clinical Sciences & Operations

This is a multicenter, parallel multicohort, phase 2, single-arm study for adjunctive treatment in participants with high-risk myeloid malignancies undergoing allogeneic HSCT. The purpose of this study is to assess the safety and preliminary efficacy of off-the-shelf (OTS) ex vivo expanded NK cells (SAR445419) in improving relapse free survival (RFS).

The expected duration of the study for a participant is about 2 years.

This is a parallel multicohort, phase 2, single-arm study.

A Study to Investigate Use of Off-the-shelf Natural Killer (NK) Cells (SAR445419) in Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

A Phase 2, Single Arm, Multicohort, Open Label, Multicenter Trial of Off-the-shelf Natural Killer (NK) Cells (SAR445419) in Patients With High-risk Myeloid Malignancies Undergoing Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Percentage of patients who are relapse free and alive at 12 months from the date of HSCT and who received at least the first 2 planned doses of SAR445419

Frequency of primary or secondary graft failure

AEs characterized by type and severity as graded by the national cancer institute common terminology criteria for adverse events (NCI CTCAE) v.5.0, timing, seriousness, and relationship to study treatments. All AEs will be captured from signing of informed consent until 30 days after the last SAR445419 administration. All serious AEs (SAEs) and AEs of special interest (AESIs) will be captured until the end of the study.

The cumulative incidence of grade 2-4 and 3-4 aGVHD

The cumulative incidence of cGVHD graded as mild, moderate or severe

The proportion of patients with full chimerism (≥95% donor cells), mixed chimerism (5-95% donor cells) and graft rejection (\<5% donor cells)

AML-QoL is a 27 item questionnaire to measure quality of life in patients with Acute Myeloid Leukemia and high-risk Myelodysplastic Syndrome, covering seven different domains and with lower scores indicating better quality of life. AML-QoL uses 5-point Likert type scale ranging from 1: "Never" to 5: "Almost always" for the 26 items included in domains and ranging from 1: "Excellent" to 5: "Poor" for the QOL item.

FACT-BMT is a 50 item questionnaire to measure quality of life in bone marrow transplant patients covering five different domains and with higher scores indicating better quality of life. FACT-BMT questionnaire uses likert type scale with responses measuring from 0-4 (where 0 = not at all; 1 = a little bit; 2 = somewhat, 3 = quite; and 4 = very much)

PGIS scale is a single-item with a self-reported categorical scale to assess patient's impression of disease severity. PGIS contains response options ranging from 0 (none) to 4 (severe).

PGIC scale is a single item with a self-reported categorical scale designed to assess patient's impression of change in disease symptom severity. PGIC contains response options ranging from 0 (no-change) to 7 (considerable improvement).

FACIT-GP5 is single item to assess global side effect bother. FACIT-GP5 uses likert type scale with responses Scores range from 0 (not at all bothered by side effect) to 4 (very much bothered by side effects).

Sanofi

Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Pharmaceutical Solutions

Cytarabine

Fludarabine

Fludarabine phosphate

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Antiviral Agents

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.

Cell suspension, by intraveneous (IV) injection

fludarabine

cytarabine

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.

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.

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

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)

Median time to neutrophil and platelet count recovery post chemotherapy

Percentage of participants going onto hematopoietic stem cell transplantation (HSCT) following SAR445419 treatment but prior to subsequent therapy for treatment of AML

Fungal, bacterial, viral, and particularly cytomegalovirus (CMV) infection or reactivation (opportunistic) infection

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 CR or a complete remission with partial hematological recovery (CRh)

Percentage of participants with CR or CRh or CRi or morphological leukemia-free state (MLFS)

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

Time interval from date of first SAR445419 administration to induction failure, relapse or death due to any cause, whichever comes first

Time from the first SAR445419 administration to death from any cause

Time from first SAR445419 administration to discontinuation for any reason excluding remission

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Study to Investigate Use of Off-the-shelf Natural Killer (NK) Cells (SAR445419) in Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)	NCT05726682	Allogenic Stem ...	SAR445419	18 Years - 75 Years	Sanofi
A Study to Investigate Use of Off-the-shelf Natural Killer (NK) Cells (SAR445419) in Relapsed/Refractory Acute Myeloid Leukemia	NCT05712278	Acute Myeloid L...	SAR445419 fludarabine cytarabine	18 Years -	Sanofi

Spots Global Cancer Trial Database for sar445419

Every month we try and update this database with for sar445419 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for sar445419

Every month we try and update this database with for sar445419 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for sar445419 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.