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Allogenic Stem Cell TransplantationPhase 2NCT05726682

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

A Phase 2 study testing SAR445419 in people with Allogenic Stem Cell Transplantation, run by Sanofi.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Allogenic Stem Cell Transplantation
What is being tested?
SAR445419
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
8 Oct 2024to 11 Oct 2027
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 11Show fewer
  • 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.

About this study

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)

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).

Read the detailed description

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

Being tested
SAR445419

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SAR445419Drug

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

Study groups in NCT05726682
Study groupRoleWhat they receive
High risk AML and MDSExperimentalParticipants 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.
Receives: Drug: SAR445419

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 12 months post HSCT

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

    Measured: From baseline up to 2 years

  3. 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

    Measured: From baseline up to 2 years

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

    Measured: From baseline up to 2 years

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

    Measured: From baseline up to 2 years

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

    Measured: From baseline up to 2 years

  7. Frequency of non-relapse mortality (NRM)

    Measured: 100 days post HSCT

  8. Frequency of graft failure

    Frequency of primary or secondary graft failure

    Measured: 100 days post HSCT

  9. Frequency of overall mortality

    Measured: 100 days post HSCT

Secondary outcomes (20)

  1. 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.

    Measured: From baseline up to 2 years

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

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

    Measured: 6, 12, 18 and 24 months post-HSCT

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

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

    Measured: 6, 12, 18 and 24 months post-HSCT

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

    Measured: 6, 12, 18 and 24 months post-HSCT

  5. Cumulative incidence of relapse

    Measured: 6, 12, 18 and 24 months post-HSCT

  6. Rate of relapse free survival (RFS)

    Measured: 6, 12, 18 and 24 months post-HSCT

  7. Rate of overall survival (OS)

    Measured: 6, 12, 18 and 24 months post-HSCT

  8. Rate of non-relapse mortality (NRM)

    Measured: 6, 12, 18 and 24 months post-HSCT

  9. Rate of GVHD-free relapse-free survival (GRFS)

    Measured: 6, 12, 18 and 24 months post-HSCT

  10. Time to hematologic recovery (platelet and neutrophil count recovery) post-HSCT

    Measured: From baseline up to approximately 180 days

  11. 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)

    Measured: 28 and 100 days, and 6 and 12 months post-HSCT

  12. Frequency of primary graft failure

    Measured: 28 days post-HSCT

  13. Frequency of secondary graft failure

    Measured: 100 days and 12, 18 and 24 months post-HSCT

  14. Cumulative incidence of CMV reactivation or infection and symptomatic BK-virus (BKV) hemorrhagic cystitis

    Measured: 100 days and 6 and 12 months post-HSCT

  15. Cumulative incidence of grade 2-4 and grade 3-4 infections during the on-treatment period

    Measured: Until 30 days after the last administration of SAR445419

  16. 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.

    Measured: 28 and 100 days and 6, 9 and 12 months post HSCT

  17. 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)

    Measured: 28 and 100 days and 6, 9 and 12 months post HSCT

  18. 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).

    Measured: 28 and 100 days and 6, 9 and 12 months post HSCT

  19. 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).

    Measured: 28 and 100 days and 6, 9 and 12 months post HSCT

  20. 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).

    Measured: 7, 14 and 35 days post-HSCT

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Feb 2023
  2. Study start8 Oct 2024 (estimated)
  3. Primary completion12 Feb 2027 (estimated)
  4. Study completion11 Oct 2027 (estimated)

Why it stopped: Sponsor decision to cancel trial, not related to safety concern.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Parallel groups
Model description
This is a parallel multicohort, phase 2, single-arm study.
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05726682
Sponsor's protocol ID
ACT17550
Other IDs
U1111-1275-1345
Status last verified
Mar 2024
First submitted
2 Feb 2023
Last updated
5 Mar 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing SAR445419 in people with Allogenic Stem Cell Transplantation, run by Sanofi.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 5 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rate of relapse free survival (RFS) post allogeneic hematopoietic stem cell transplantation (HSCT) (time frame: 12 months post HSCT). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05726682.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2024.

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