Clinical trial NCT05726682: A Study to Investigate Use of Off-the-shelf Natural Killer (NK) Cells (SAR445419) in Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Allogenic Stem Cell Transplantation
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2023-02-14
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: PARALLEL
Intervention model description: This is a parallel multicohort, phase 2, single-arm study.
Primary purpose: TREATMENT

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).

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

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Rate of relapse free survival (RFS) post allogeneic hematopoietic stem cell transplantation (HSCT)
timeFrame: 12 months post HSCT
measure: Frequency of cytomegalovirus (CMV) reactivation/infection in CMV seronegative participants who receive a CMV seronegative HSCT graft
timeFrame: From baseline up to 2 years
measure: 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
timeFrame: From baseline up to 2 years
measure: Frequency of life threatening (grade 4) tumor lysis syndrome (TLS)
timeFrame: From baseline up to 2 years
measure: Frequency of life-threatening (grade 4) immune cell-associated neurotoxicity syndrome (ICANS) that does not resolve to grade 1 within 72 hours despite therapy
timeFrame: From baseline up to 2 years
measure: Frequency of grade 3-4 acute graft versus host disease (aGVHD)
timeFrame: From baseline up to 2 years
measure: Frequency of non-relapse mortality (NRM)
timeFrame: 100 days post HSCT
measure: Frequency of graft failure
timeFrame: 100 days post HSCT
measure: Frequency of overall mortality
timeFrame: 100 days post HSCT
Secondary outcomes:
measure: Frequency of adverse events (AEs)
timeFrame: From baseline up to 2 years
measure: Number of participants with acute Graft-Versus-Host-Disease (aGVHD)
timeFrame: 6, 12, 18 and 24 months post-HSCT
measure: Number of participants with chronic Graft-Versus-Host-Disease (cGVHD)
timeFrame: 6, 12, 18 and 24 months post-HSCT
measure: Proportion of participants who are alive and do not need ongoing immune suppression to control GVHD
timeFrame: 6, 12, 18 and 24 months post-HSCT
measure: Cumulative incidence of relapse
timeFrame: 6, 12, 18 and 24 months post-HSCT
measure: Rate of relapse free survival (RFS)
timeFrame: 6, 12, 18 and 24 months post-HSCT
measure: Rate of overall survival (OS)
timeFrame: 6, 12, 18 and 24 months post-HSCT
measure: Rate of non-relapse mortality (NRM)
timeFrame: 6, 12, 18 and 24 months post-HSCT
measure: Rate of GVHD-free relapse-free survival (GRFS)
timeFrame: 6, 12, 18 and 24 months post-HSCT
measure: Time to hematologic recovery (platelet and neutrophil count recovery) post-HSCT
timeFrame: From baseline up to approximately 180 days
measure: Frequency of donor cell engraftment
timeFrame: 28 and 100 days, and 6 and 12 months post-HSCT
measure: Frequency of primary graft failure
timeFrame: 28 days post-HSCT
measure: Frequency of secondary graft failure
timeFrame: 100 days and 12, 18 and 24 months post-HSCT
measure: Cumulative incidence of CMV reactivation or infection and symptomatic BK-virus (BKV) hemorrhagic cystitis
timeFrame: 100 days and 6 and 12 months post-HSCT
measure: Cumulative incidence of grade 2-4 and grade 3-4 infections during the on-treatment period
timeFrame: Until 30 days after the last administration of SAR445419
measure: Change from baseline in Quality of life in Acute Myeloid Leukemia (AML-QoL) score
timeFrame: 28 and 100 days and 6, 9 and 12 months post HSCT
measure: Change from baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) score
timeFrame: 28 and 100 days and 6, 9 and 12 months post HSCT
measure: Change from baseline in Patient Global Impression of Severity (PGIS) score
timeFrame: 28 and 100 days and 6, 9 and 12 months post HSCT
measure: Change from baseline in Patient Global Impression of Change (PGIC) score
timeFrame: 28 and 100 days and 6, 9 and 12 months post HSCT
measure: Change from baseline in Functional Assessment of Chronic Illness Therapy GP5 question (FACIT-GP5) score
timeFrame: 7, 14 and 35 days post-HSCT
Other outcomes:
Locations:
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: