nkx101, intravenous allogeneic car nk cells, in adults with aml or mds

Conditions: Relapsed/Refractory AML; AML, Adult; MDS; Refractory Myelodysplastic Syndromes

Summary: this is a single-arm, open-label, multi-center, phase 1 study to determine safety and tolerability of an experimental therapy called nkx101 (allogeneic car nk cells targeting nkg2d ligands) in patients with relapsed/refractory aml or intermediate, high and very high risk relapsed/refractory mds.

this is a dose-finding study of nkx101 and will be conducted in 2 parts: part 1: dose finding with two dosing regimens, utilizing modified "3+3" enrollment schema. part 2: dose expansion to further evaluate safety and tolerability, cellular kinetics, pharmacodynamics and anti-tumor response in expansion cohorts of patients with either aml or mds.

Eligibility criteria:
inclusion criteria: * 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 exclusion criteria: * disease related: * acute promyelocytic leukemia with t(15;17) (q22;q12); or abnormal promyelocytic leukemia/retinoic acid receptor alpha (apml-rara) and aml arising from chronic myelomonocytic leukemia (cmml) * evidence of leukemic meningitis or known active central nervous system disease * peripheral leukocytosis with ≥ 20,000 blasts/μl or other evidence of rapidly progressive disease that would preclude subject from completing at least 1 cycle of treatment * use of any anti-aml/mds chemotherapeutic or targeted small molecule drug within protocol specified window prior to the first dose of nkx101 * presence of residual non-hematologic toxicity from prior therapies that has not resolved to ≤ grade 1 * any hematopoietic cell transplantation within 16 weeks * other comorbid conditions and concomitant medications prohibited as per study protocol * other: * pregnant or lactating female

Keywords: nkg2d car allogeneic natural killer acr nkx101 il15 interleukin 15 nk cell cell therapy immunotherapy adoptive cell therapy r/r aml off-the-shelf