Allogeneic iNKT Cell Therapy (agenT-797) After SCT

This study is being done to assess the safety and determine the maximum tolerated dose (MTD) of allogeneic invariant natural killer T (iNKT) cell therapy (agenT-797) in patients undergoing allogeneic hematological SCT.

• agenT-797 (Drug): agenT-797 is an off-the-shelf cell therapy consisting of ≥ 95% allogeneic human unmodified iNKT cells isolated from 1 healthy donor mononuclear cell apheresis unit and expanded ex vivo.

Primary outcomes

• Number Of Participants With Treatment-related Adverse Events [Baseline through Day 29 post cell infusion]: This will be determined by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0.
• Number Of Dose-limiting Toxicities [Baseline through Day 29 post cell infusion]

Secondary outcomes

• Incidence of grade II-IV acute graft-versus-host disease (aGVHD) [Baseline through Day 29 post cell infusion]
• Incidence of severe grade III-IV aGVHD [Baseline through Day 29 post cell infusion]
• Progression-free Survival (PFS) [12 months]: 1-year PFS is the percentage of patients who are alive and whose cancer has not progressed within one year after receiving agenT-797.
• Non-relapse Mortalilty (NRM) [12 months]: NRM is percentage of patients who died without recurrent or progressive disease after allo-SCT.
• Relapse-free Survival (RFS) [12 months]: RFS is the length of time from agenT-797 administration until disease relapse or death.
• Overall survival (OS) [12 months]: OS is the time from agenT-797 administration until death due to any cause.
• Immune reconstitution based on lymphocyte subset panel [12 months]
• Immunoglobulin levels [12 months]: Immune reconstitution measured through quantitative immunoglobulin levels
• Incidence of treatment-emergent adverse event (TEAE) infection [Baseline to 29 days post cell infusion]
• Type of infection [Baseline to 29 days post cell infusion]: Description of type of infection, e.g., bacterial, viral, or fungal.
• Donor Chimerism [Baseline to 29 days post cell infusion]: Donor chimerism will be assessed and categorized as full/complete chimerism (DNA ≥ 95% donor in CD3+ compartment) or mixed chimerism (DNA < 95% donor in CD3+ compartment).
• Absolute neutrophil count (ANC) [Baseline to 29 days post cell infusion]
• Non-relapse mortality rate (NRM) [100 days]: NRM is percentage of participants who died without recurrent or progressive disease within 100 days after allo-SCT.
• Relapse rate [100 days]: Relapse rate is percentage of participants who relapsed within 100 days after allo-SCT
• GVHD incidence [100 days]: GVHD incidence rate at day 100 post SCT is the percentage of participants who experienced GVHD within 100 days after allo-SCT

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Age ≥18 years at the time of consent
* Adult patients anticipated to get an allogeneic hematopoietic cell transplantation (allo-SCT)
* All donor types are accepted (MMUD \[mismatched unrelated donor\], MUD \[matched unrelated donor\], MSD \[matched sibling donor\], haploidentical)
* All conditioning regimens will be accepted (MAC \[myeloablative conditioning\], RIC \[reduced-intensity conditioning\], NMAC \[non-myeloablative conditioning\])
* Karnofsky Performance Scale (KPS) > 70
* Eligible Diagnoses:

  * Acute myeloid leukemia (AML) with intermediate/high-risk features or relapsed disease
  * Chronic myeloid leukemia (CML) in accelerated or blast phases
  * Myelodysplastic syndrome (MDS) with intermediate/high-risk features
  * Acute lymphoblastic leukemia (ALL) with high-risk features or relapsed disease
  * or any patients undergoing allogeneic stem cell transplant (allo-SCT) as standard of care could be eligible

Exclusion Criteria:

* Excluded Diagnoses: Primary Myelofibrosis in the dose escalation phase and could be included in the dose-expansion phase

• Hongtau Liu, MD, PhD, Principal investigator, University of Wisconsin, Madison