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

NCT05726682 | Withdrawn Phase 2 FDA Drug

• 2 other identifiers: ACT17550U1111-1275-1345
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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).

Conditions

Allogenic Stem Cell Transplantation

Outcome Measures

Primary Outcomes (9)

• Rate of relapse free survival (RFS) post allogeneic hematopoietic stem cell transplantation (HSCT)

  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

  12 months post HSCT

• Frequency of cytomegalovirus (CMV) reactivation/infection in CMV seronegative participants who receive a CMV seronegative HSCT graft

  From baseline up to 2 years

• Frequency of life-threatening (grade 4) infusion related reactions (IRR) or cytokine release syndrome (CRS) that does not resolve to grade 1 within 72 hours despite therapy

  From baseline up to 2 years

• Frequency of life threatening (grade 4) tumor lysis syndrome (TLS)

  From baseline up to 2 years

• Frequency of life-threatening (grade 4) immune cell-associated neurotoxicity syndrome (ICANS) that does not resolve to grade 1 within 72 hours despite therapy

  From baseline up to 2 years

• Frequency of grade 3-4 acute graft versus host disease (aGVHD)

  From baseline up to 2 years

• Frequency of non-relapse mortality (NRM)

  100 days post HSCT

• Frequency of graft failure

  Frequency of primary or secondary graft failure

  100 days post HSCT

• Frequency of overall mortality

  100 days post HSCT

Secondary Outcomes (20)

• Frequency of adverse events (AEs)

  From baseline up to 2 years

• Number of participants with acute Graft-Versus-Host-Disease (aGVHD)

  6, 12, 18 and 24 months post-HSCT

• Number of participants with chronic Graft-Versus-Host-Disease (cGVHD)

  6, 12, 18 and 24 months post-HSCT

• Proportion of participants who are alive and do not need ongoing immune suppression to control GVHD

  6, 12, 18 and 24 months post-HSCT

• Cumulative incidence of relapse

  6, 12, 18 and 24 months post-HSCT

Study Arms (1)

High risk AML and MDS

EXPERIMENTAL

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.

Drug: SAR445419

Interventions

SAR445419 DRUG

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

High risk AML and MDS

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-65 (Cohort A - MAC) or 18-75 (Cohort B - RIC)
• Participants with high-risk AML/MDS who are scheduled to undergo stem cell transplantation with matched sibling donor (MSD), matched unrelated donor (MUD) or haploidentical donor sourced HSCT
• Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) ≤ 3 (cohort A / MAC participants only)
• Adequate major non-hematopoietic organ system function
• Karnofsky performance score ≥70%
• Body weight ≥45 kg

You may not qualify if:

• AML beyond CR1
• Presence of FLT3 mutations
• Uncontrolled bacterial, viral, or fungal infections at time of enrollment
• Positive test for human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS)
• Positive hepatitis B virus (HBV) or hepatitis C virus (HCV) indicating acute or chronic infection
• Diagnosis of prior immunodeficiency or organ transplantation requiring immunosuppressive therapy
• Active or chronic autoimmune condition requiring systemic immunosuppressive or immunomodulatory therapy
• Prior allogeneic transplantation
• HSCT graft DSA ≥3000 MFI
• Current use of systemic corticosteroids at physiologic doses ≤ 0.2 mg/kg/day of prednisone or equivalent
• Use of checkpoint inhibitor therapy within 4 weeks prior to the start of HSCT conditioning regimen The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Sponsors & Collaborators

• Sanofi: lead

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: February 2, 2023
• First Posted: February 14, 2023
• Study Start: October 8, 2024
• Primary Completion (Estimated): February 12, 2027
• Study Completion (Estimated): October 11, 2027
• Last Updated: March 5, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share