NKARTA: This Phase I trial is evaluating how safe and tolerable an experimental targeted therapy (NKX101) is in people with acute myeloid leukaemia or myelodysplastic syndromesA Phase 1 Study of NKX101, an Activating Chimeric Receptor Natural Killer Cell Therapy, in Subjects With Hematological Malignancies or Dysplasias

Inclusion

• General:

  • ECOG performance status ≤2

• Disease related:

  • For AML subjects:

    • Previously treated relapsed/refractory AML, including subjects with MRD+ disease
    • Received at most 3 lines of previous anti-leukemia therapy
    • For subjects with targetable fms-like tyrosine kinase 3 (FLT3)-mutated or isocitrate dehydrogenase (IDH)1/2 mutated disease, subjects must have received at least 1 prior respective targeted therapy and may receive up to 4 lines of prior therapy
    • White blood cell count of ≤25 × 10^9/L
    • For groups receiving NKX101 after lymphodepletion with fludarabine/cyclophosphamide +/- decitabine: Disease localized to the bone marrow, as evidenced by ≤ 5% peripheral blasts and no evidence of extramedullary disease
    • For groups receiving NKX101 after lymphodepletion with fludarabine/ cyclophosphamide +/- decitabine, group receiving NKX101 after lymphodepletion with fludarabine/ara-C: Additional subjects with specifically high-risk genetic mutations may be enrolled. High risk genetic mutation per ELN 2022 should be evaluated as per local assay and discussed with the Sponsor prior to study entry
    • For groups receiving NKX101 after lymphodepletion with fludarabine/cyclophosphamide +/- decitabine, group receiving NKX101 after lymphodepletion with fludarabine/ara-C: Additional subjects who have relapsed following HCT may be enrolled.

  • For MDS subjects:

    • Intermediate-, high-, or very high-risk MDS
    • Previously treated relapsed/refractory MDS
    • Received at least 1 and at most 3 lines of previous standard anti-MDS therapy
    • For groups receiving NKX101 after lymphodepletion with fludarabine/ cyclophosphamide +/- decitabine: Additional subjects with specifically high-risk disease may be enrolled. High-risk genetic mutation should be evaluated as per local assay
    • For group receiving lymphodepletion with fludarabine/cyclophosphamide +/- decitabine and NKX101: Additional subjects who have relapsed following HCT may be enrolled.
• Adequate Organ Function
• Platelet count ≥30,000/uL (platelet transfusions acceptable)

• Other:

  • Signed informed consent
  • Agree to use an effective barrier method of birth control