An interventional study of Infusion of alloreactive NK cells in Acute Myeloid Leukemia, Minimal Residual Disease and Natural Killer Cell, sponsored by IRCCS Azienda Ospedaliero-Universitaria di Bologna. Recruiting at 1 site in Italy. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-03-20.
Sponsored by IRCCS Azienda Ospedaliero-Universitaria di Bologna · Not applicable, Interventional, and Treatment
This is a interventional, transplantation study. The procedure under study is the infusion of alloreactive NK cells in adult AML patients, eligible for ASCT, who achieved CR after conventional chemotherapy, but harbor MRD-positivity.
Haploidentical KIR-L mismatched donors will be included if present at least one allele mismatch at a class I locus among the following ones: HLA-C alleles with Asn77-Lys80, HLA-C alleles with Ser77-Asn80, HLA-Bw4 alleles. KIR-L mismatched donor alloreactive NK cell repertoire will be evaluated in order to determine the functional cell dose to be used for NK cell collection. Phenotypical analysis of KIRs will be correlated to functional tests. NK cells will be selected from a steady-state large volume leukapheresis product from a suitable haploidentical KIR-ligand incompatible donor. NK cell purification will be performed if the donor leukapheresis product contains at least 10x106 NK cells/Kg.
Immunomagnetic enrichment of NK cells will follow two subsequent steps: 1) depletion of CD3+ T cells followed by 2) positive selection of CD56+ NK cells.
Patients will receive immunosuppressive chemotherapy, fludarabine (Flu) 25 mg/mq/ from day -5 to -3 and cyclophosphamide (Cy) 2 g/mq on day -2 (Flu/Cy). Two days after Cy administration, patients will be infused intravenously with a single dose of cryopreserved NK cells (day 0), which will be followed by subcutaneous administration of IL-2 (10 x 106 IU/day, 3 times weekly) for 2 weeks (6 doses total). PB samples will also be collected for biological studies. In particular, PB samples will be collected for molecular assessment of microchimerism and tracking of haploidentical NK cells for 30 days, immunophenotype studies, alloreactive NK cells cloning and functional assays (cytotoxicity). Enrolled patients will be followed up for at least 12 months after NK cell infusion.
5,441 studies on the registry are indexed under Leukemia; 636 are open to participants now.
This study's planned enrollment of 22 is below the median of 38 across 4,247 interventional studies indexed under Leukemia.
Browse Leukemia studies →IRCCS Azienda Ospedaliero-Universitaria di Bologna is the lead sponsor of 493 studies on the registry; 273 are open to participants now.
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Exclusion Criteria:
Infusion of alloreactive NK cells for acute leukemia patients, eligible for allogeneic stem cell transplantation, with persistent minimal residual disease after conventional chemotherapy
Biological: Infusion of alloreactive NK cells
Infusion of alloreactive NK cells for acute leukemia patients harboring minimal residual disease after conventional chemotherapy and prior to allogeneic stem cell transplantation
Safety of infusing a functional target cell dose of 2x105 alloreactive NK cells/kg in AML patients,eligible for ASCT, with persistent MRD after conventional chemotherapy
Safety of infusing a functional target cell dose of 2x105 alloreactive NK cells/kg in AML patients,eligible for ASCT, with persistent MRD after conventional (number of adverse events and severe adverse events)
Time frame: 48 months
Feasibility of collecting a functional target cell dose of 2x105 alloreactive NK cells/kg in at least 70% of patients entering the study
Feasibility of collecting a functional target cell dose of 2x105 alloreactive NK cells/kg in at least 70% of patients entering the study as evaluated by in vitro cytotoxicity assay.
Time frame: 48 months
Number of patients who achieve and maintain MRD negativity after infusion of alloreactive NK cells
Number of patients who achieve and maintain MRD negativity after infusion of alloreactive
Time frame: 48 months
Number of patients who enter ASCT in MRD-negativity
Number of patients who enter ASCT in MRD-negativity
Time frame: 48 months
Relapse-free survival (RFS) of patients infused with alloreactive NK cells
Relapse-free survival (RFS)of patients infused with alloreactive NK cells
Time frame: 48 months
overall survival (OS) of patients infused with alloreactive NK cells
overall survival (OS) of patients infused with alloreactive NK cells
Time frame: 48 months
Assess the predictive impact of donor NK cell repertoire on overall survival
Assess the predictive impact of donor NK cell repertoire as evaluated as the number of alloreactive NK cells/kg, in terms of overall survival
Time frame: 48 months
Assess the predictive impact of donor NK cell repertoire on relapse-free survival
Assess the predictive impact of donor NK cell repertoire as evaluated as the number of alloreactive NK cells/kg, in terms of relapse-free survival
Time frame: 48 months
Evaluate the microchimerism of patients receiving human NK cells
Evaluate the microchimerism of patients receiving human NK cells, as evaluated as percent of donor's cells into recipients
Time frame: 48 months
Functionally evaluate, in vitro and ex vivo, the antitumor activity of infused NK cells
Functionally evaluate, in vitro and ex vivo, the antitumor activity of infused NK cells, as evaluated by in vitro cytotoxicity assay (percent of lysis by donor NK cells of recipients cells).
Time frame: 48 months
Assess the molecular features of infused NK cells
Assess the molecular features of infused NK cells, qualitative gene expression profile.
Time frame: 48 months
Plan to share: No
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IRCCS Azienda Ospedaliero-Universitaria di Bologna