Inclusion Criteria:
- 18-74 years with Karnofsky score ≥ 70%
- 75 years and older: KPS ≥ 70%, HCT-CI < 5 (excluding history of solid tumor), AND not frail by Fried frailty criteria (see Appendix III)
- HLA type C1/C1 or C2/C2
Note: For easy determination, the definition of HLA-C ligand group assigments is included below:
HLA-C1 group alleles are defined as HLA-C01, C03, C07, C08, C12, C14, C16 HLA-C2 group alleles are defined as HLA-C02, C04, C05, C06, C15, C17, C18
- adequate liver, renal, pulmonary and cardiac function
- ability to be off glucocorticoids and other immunosuppressive medications indicated for acute or chronic GVHD for at least 28 days prior to the AdaptNK cell infusion
- There must be sufficient time between the most recent therapy and the screening bone marrow as delineated below:
- anti-leukemic systemic cytotoxic chemotherapy - 2 weeks
- Targeted anti-leukemic agents (FLT-3, IDH, menin inhibitors) - 3 half-lives of the medication
- Radiotherapy - 1 week
- donor lymphocyte infusions - 6 weeks
- hematopoietic growth factors (filgrastim, TPO agonists, EPO) - 1 week
- biologic therapy (monoclonal antibodies, T-cell engagers) - 2 weeks
- Immune effector cellular therapy - 4 weeks
- Intrathecal chemotherapy for treatment of active CNS leukemia - there must be at least two CSF samples negative for leukemia separated by one week before enrollment.
- WBC shall be < 25,000 before infusion. Hydroxyurea is permitted until day -3 to control excess blast proliferation. No other systemic treatment is allowed after the screening bone marrow is performed for inclusion in protocol
- All prior treatment related toxicities should have resolved to ≤ grade 1 prior to study enrollment
- agrees to use of adequate contraception from study enrollment to 4 months after cell infusion
- voluntary written consent
Exclusion Criteria:
- Myeloid neoplasms with known or strongly suspected germline background, except DDX41, TP53, or RUNX1.
- Acute promyelocytic leukemia (APL)
- myocardial infarction (MI) within previous 6 months of study enrollment
- pregnant or breastfeeding
- Active CNS involvement with AML
- new or progressive pulmonary infiltrates
- active autoimmune disease requiring immunosuppressive therapy
- Preexisting inflammatory disease requiring immunosuppressive therapy
- history of severe asthma and currently on chronic systemic medications
- HIV-1/2 positivity or hepatitis C/B
- active systemic infections requiring anti-infective treatment
- received any investigational agent within the 14 days before the start of study treatment (1st dose of fludarabine)
- Patients with second malignancies are excluded if they have required systemic cytotoxic chemotherapy within 1 year or if they are not in remission
- Exception: patients that are on stable dosing of hormonal therapy (e.g. aromatase inhibitor or antiandrogen therapy) for active breast or prostate cancer for 1 year are eligible.
- Patients with excised basal cell or squamous cell carcinoma of the skin are eligible.
- Patients with excised carcinoma in situ of the cervix or breast are eligible.
- Patients with untreated T1a or T1b prostate cancer are eligible.