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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Pharmaceutical form: cell suspension Route of administration: Intravenous (IV) injection
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
Time frame: 12 months post HSCT
Frequency of cytomegalovirus (CMV) reactivation/infection in CMV seronegative participants who receive a CMV seronegative HSCT graft
Time frame: 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
Time frame: From baseline up to 2 years
Frequency of life threatening (grade 4) tumor lysis syndrome (TLS)
Time frame: 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
Time frame: From baseline up to 2 years
Frequency of grade 3-4 acute graft versus host disease (aGVHD)
Time frame: From baseline up to 2 years
Frequency of non-relapse mortality (NRM)
Time frame: 100 days post HSCT
Frequency of graft failure
Frequency of primary or secondary graft failure
Time frame: 100 days post HSCT
Frequency of overall mortality
Time frame: 100 days post HSCT
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Frequency of adverse events (AEs)
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.
Time frame: From baseline up to 2 years
Number of participants with acute Graft-Versus-Host-Disease (aGVHD)
The cumulative incidence of grade 2-4 and 3-4 aGVHD
Time frame: 6, 12, 18 and 24 months post-HSCT
Number of participants with chronic Graft-Versus-Host-Disease (cGVHD)
The cumulative incidence of cGVHD graded as mild, moderate or severe
Time frame: 6, 12, 18 and 24 months post-HSCT
Proportion of participants who are alive and do not need ongoing immune suppression to control GVHD
Time frame: 6, 12, 18 and 24 months post-HSCT
Cumulative incidence of relapse
Time frame: 6, 12, 18 and 24 months post-HSCT
Rate of relapse free survival (RFS)
Time frame: 6, 12, 18 and 24 months post-HSCT
Rate of overall survival (OS)
Time frame: 6, 12, 18 and 24 months post-HSCT
Rate of non-relapse mortality (NRM)
Time frame: 6, 12, 18 and 24 months post-HSCT
Rate of GVHD-free relapse-free survival (GRFS)
Time frame: 6, 12, 18 and 24 months post-HSCT
Time to hematologic recovery (platelet and neutrophil count recovery) post-HSCT
Time frame: From baseline up to approximately 180 days
Frequency of donor cell engraftment
The proportion of patients with full chimerism (≥95% donor cells), mixed chimerism (5-95% donor cells) and graft rejection (\<5% donor cells)
Time frame: 28 and 100 days, and 6 and 12 months post-HSCT
Frequency of primary graft failure
Time frame: 28 days post-HSCT
Frequency of secondary graft failure
Time frame: 100 days and 12, 18 and 24 months post-HSCT
Cumulative incidence of CMV reactivation or infection and symptomatic BK-virus (BKV) hemorrhagic cystitis
Time frame: 100 days and 6 and 12 months post-HSCT
Cumulative incidence of grade 2-4 and grade 3-4 infections during the on-treatment period
Time frame: Until 30 days after the last administration of SAR445419
Change from baseline in Quality of life in Acute Myeloid Leukemia (AML-QoL) score
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.
Time frame: 28 and 100 days and 6, 9 and 12 months post HSCT
Change from baseline in Functional Assessment of Cancer Therapy - Bone Marrow Transplantation (FACT-BMT) score
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)
Time frame: 28 and 100 days and 6, 9 and 12 months post HSCT
Change from baseline in Patient Global Impression of Severity (PGIS) score
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).
Time frame: 28 and 100 days and 6, 9 and 12 months post HSCT
Change from baseline in Patient Global Impression of Change (PGIC) score
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).
Time frame: 28 and 100 days and 6, 9 and 12 months post HSCT
Change from baseline in Functional Assessment of Chronic Illness Therapy GP5 question (FACIT-GP5) score
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).
Time frame: 7, 14 and 35 days post-HSCT