Infusion of Alloreactive nk Cells for Mrd-positive Aml Patients

Condition(s) studied

Investigational drug(s) / intervention(s)

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

Study summary

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.

Eligibility

Primary outcome measure(s)

• 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 — 48 months
  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)
• Feasibility of collecting a functional target cell dose of 2x105 alloreactive NK cells/kg in at least 70% of patients entering the study — 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 as evaluated by in vitro cytotoxicity assay.

Trial sites (1)

More IRCCS Azienda Ospedaliero-Universitaria di Bologna trials in Italy

Other trials for the same condition