15353-j-veluchamy

18 | Chapter 1 Table 2: Summary of allogeneic NK cell clinical trials in a non-transplantation setting Study Malignancy Clinical Trial design Culture method* Phase I (EudraCT number: 2010-018988-41) Dolstra et al ref 72 AML (n=10) Conditioning with Cy/Flu followed by KIR mismatched UCB-NK-cell infusion Ex vivo expanded, differentiated and activated UCB-NK cells from unrelated donors. Culture duration: 42 days with GM-CSF, G-SCF, IL-6, SCF, Flt3L, TPO, IL-7, IL-2 and IL-15 *CD34+ selected HSPC’s Phase I (NCT01898793) Romee et al (2016) ref 73 AML (n=13) Conditioning with Cy/Flu followed by cytokine induced memory-like NK-cell infusion and subsequent IL-2 therapy (every other day, 6x) Ex vivo expanded and activated PBNK-cells from haploidentical donors. Culture duration :12- 16h with IL-15, IL-12 and IL- 18. *CD3 depleted and CD56 selected Phase I (NCT00799799) Curti et al (2016) ref 74 AML (n=16) Conditioning with Cy/ Flu followed by KIR ligand mismatched NK-cell infusion; IL-2 therapy (3x weekly for 2 weeks) PBNK-cells from haploidentical donors. *CD3 depleted and CD56 selected Phase II (NCT00526292) Shaffer et al (2016) ref 75 AML (n=6) and MDS (n=2) Conditioning with Cy/Flu followed by HLA-mismatched NK-cell infusion; IL-2 therapy (6x) starting 1 day before and after NK-cell infusion PBNK-cells from haploidentical donors. *CD3 depleted and CD56 selected Phase I (NCT01212341) Yang et al (2016) ref 76 Lymphoma (n=2) and solid tumor (n=18) KIR ligand mismatched NK cell infusion Ex vivo expanded and activated PBNK-cells from unrelated donors. Culture duration: 14 days with irradiated auto- PBMCs, OKT3 and IL-2 Phase I (NKAML: NCT00697671) Pilot study (NKHEM: NCT00187096) Rubnitz et al (2015) ref 77 Relapsed Leukemia post HSCT (n=15) Refractory/relapsed leukemia (no prior HSCT) (n=14) Conditioning with Clo/Eto/Cy followed by KIR matched or mismatched NK-cell infusion; IL-2 therapy (6x) starting 1 day before and after NK-cell infusion Ex vivo expanded PBNK-cells from haploidentical donors. Culture duration :>12h. *CD3 depleted and CD56 selected Phase I (EudracT number: 2005-006087-62) Kottaridis et al (2015) ref 78 AML (n=7) Conditioning with Flu and TBI followed by haploidentical tumor primed NK-cell infusion Ex vivo expanded and activated PBNK-cells from haploidentical donors. Culture duration: o/n with CTV-1 lysate and cryopreserved for infusion. *Only CD56 selected