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14 | Chapter 1 Table 1: Summary of allogeneic NK cell clinical trials in a transplantation setting Study Malignancy Clinical Trial design Culture method* Phase I (NCT01729091) Shah et al (2017) ref 64 MM (n=12) Conditioning with Mel on day -7 and Lnd from days -8 to -2 prior to UCB- NK cell infusion (day -5), followed by autologous-HSCT on day 0 Ex vivo expanded MNCs from unrelated UCB donors. Culture duration: 14 days with irradiated K562 clone 9.mbIL-21 aAPCs and IL-2 *CD3 depleted (on day 7) Phase I (NCT01795378) Choi et al (2016) ref 65 AML (n=45) and ALL (n=6) Haplo-HSCT followed by DNKI from the same donor on day 6, 9, 13 and 20 post HSCT Ex vivo expanded and activated PBNK-cells from haploidentical donors. Culture duration :2-3 weeks with IL-15 and IL-21 Phase I (NCT00402558) Lee et al (2016) Phase II (NCT01390402) ref 66 AML (n=8), MDS (n=6) and CML (n=7) Conditioning with Flu/Bu prior to haplo- allo NK-cell infusion, followed by IL-2 therapy (5x, daily); conditioning with Thy/Tac prior to HLA matched related unrelated allo-HSCT Ex vivo expanded and activated PBNK-cells from haploidentical donors. Culture duration: o/n with IL-2. *CD3 depleted and CD56 selected (in 3 infusions) Phase I (NCT01287104) Shah et al (2015) ref 67 EWS (n=5), DSRCT (n=3), RMS (n=1) HLA matched haplo- or unrelated allo-HSCT followed by aNK-DLI from the same donor on day 7 and 35 post HSCT Ex vivo expanded and activated PBNK-cells from haploidentical donors. Culture duration :9-11 days with KT64.4-BBL artificial antigen presenting cells. *CD3 depleted and CD56 selected Phase I/II (NCT01220544) Killig et al (2014) ref 68 AML (n=24) Haplo-HSCT followed by NK-cell infusion from same donor and OKT3 treatment from days -5 to+3 PBNK-cells from haploidentical donors. *CD3 depleted and CD56 selected Phase I/II (NCT00823524) Choi et al (2014) ref 69 AML (n=32), ALL (n=7), MDS (n=1), DLBCL (n=1) HLA haplo-HSCT followed by DNKI from the same donor, 14 days and 21 days after HSCT Ex vivo expanded and activated PBNK-cells from haploidentical donors. Culture duration :13-20 days with IL-15, IL-21 and hydrocortisone. Phase I (IND # 12971) Klingemann et al (2013) ref 70 NHL (n=6), MM (n=5) and HL (n=2) MHC-mismatched haploidentical NK-MC infusion, 49-191 days post auto-HSCT Ex vivo expanded and activated PBNK-cells from haploidentical donors. Culture duration: o/n with IL-2 Phase II (NCT01386619) Stern et al (2012) ref 71 AML (n=8), ALL (n=5), HL (n=2) sarcoma(n=1) Haplo-HSCT followed by NK-DLI from the same donor, +day 3, +day 40 and +day 100 post HSCT PBNK-cells from haploidentical donors. *CD3 depleted and CD56 selected Phase I/II (NCT01386619) Brehm et al (2011) ref 56 AML (n=6), ALL (n=5), NB (n=5), RMS (n=1) HL (n=1) Haplo-HSCT followed by IL-2 stimulated NK-cell infusion (cryo) or unstimulated NK-cell infusion (fresh) from the same donor, +day 3, +day 40 and +day 100 post HSCT Ex vivo expanded and activated PBNK-cells from haploidentical donors. Culture duration :9-14 days with (group II) or without (group I) IL-2 (fresh or cryo). *CD3 depleted and CD56 selected