Patients with relapsed/refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) will receive lymphodepleting chemotherapy (Flu/Cy) and two infusions of cytokine-induced memory-like NK cells at the previously defined maximum tolerated dose (MTD), fourteen days apart. Low dose rhIL-2 will be administered to patients for in vivo expansion following cell infusion. Patients will be assessed for anti-leukemic efficacy and safety. Re-infusion of patients who relapsed after clinical response will be considered.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Cell product processing is performed at the Siteman Cancer Center Biological Therapy Core or another FACT-accredited cellular therapy production facility that can manufacture the product per the IND CMC.
-Lymphodepleting regimen
-Lymphodepleting regimen
Overall response rate (ORR) of recipients
* Defined as the proportion of patients achieving complete remission (CR), complete remission with partial hematologic recovery (CRh), and complete remission with incomplete blood count recovery (CRi). * Response will be assessed according to the criteria from the International Working Group Response Criteria
Time frame: Through 12 month follow-up
Overall survival (OS) of recipients
-Defined as time from first dose of lymphodepleting chemotherapy (LDC) until death from any cause
Time frame: Through completion of follow-up (estimated to be 12 months)
Event free survival (EFS) of recipients
-Defined as time from first dose of lymphodepleting chemotherapy (LDC) until treatment failure, relapse from complete response, or death
Time frame: Through completion of follow-up (estimated to be 12 months)
Duration of overall response (DOR) of recipients
-Defined as duration for first occurrence of documented ORR until disease progression or death
Time frame: Through 12 month follow-up
Duration of complete response (DoCR) of recipients
-Defined as duration from documented complete remission until disease progression or death
Time frame: Through 12 month follow-up
Proportion of recipients that receive multiple doses of NK cell product
Time frame: Through Day +14 of all recipients enrolled (estimated to be 19 months)
Number of dose-limiting toxicities (DLTs) that recipients experience in the safety lead-in cohort
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
-Apheresis will be performed via peripheral IVs or central line, as determined by the apheresis team.
-IL-2 will start approximately 2-4 hours after the NK cell infusions.
Time frame: Through Day 28
Mortality rate of recipients
Time frame: Day +30
Mortality rate of recipients
Time frame: Day +100
Number of adverse events experienced by recipients
* Incidence, nature, and severity of adverse events * Adverse events will be collected from Day 0 to Day +35; however, bone marrow suppression (ANC \< 500/µL) and adverse events of graft-versus-host disease (GVHD) involving the liver, skin, or gastrointestinal tract will be recorded until Day +100.
Time frame: Through Day +100
Proportion of recipients with prolonged cytopenia
Time frame: At 8 weeks
Change in quality of life experienced by recipients as measured by the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30)
Time frame: Day 0, Day +28, Day +100, 6 months, 9 months, and 12 months
Overall response rate (ORR) of recipients compared across subgroups
* Subgroups will be defined by degree of HLA-match from allogeneic donor * Defined as the proportion of patients achieving complete remission (CR), complete remission with partial hematologic recovery (CRh), and complete remission with incomplete blood count recovery (CRi). * Response will be assessed according to the criteria from the International Working Group Response Criteria
Time frame: Through 12 month follow-up
Number of adverse events experienced by recipients compared across subgroups
* Subgroups will be defined by degree of HLA-match from allogeneic donor * Incidence, nature, and severity of adverse events * Adverse events will be collected from Day 0 to Day +35; however, bone marrow suppression (ANC \< 500/µL) and adverse events of graft-versus-host disease (GVHD) involving the liver, skin, or gastrointestinal tract will be recorded until Day +100.
Time frame: Through Day +100