Table 2.

Viral specific therapy clinical trials in transplantation

Clinical trial No	Author & Year	Phase	Patients and characteristics, n	Indication	Targeted Viruses	Source	Results	Safety (GvHD, CRS, Death)
	Haque 2007 [85]	Phase II	31 SOTRs and 2 HSCT recipients with PTLD	EBV-PTLD	EBV	Third-party 2 × 106/kg	64% ORR at 5w 52% ORR at 6 m 76% overall survival at 6 m	None
NCT01070797	Gerdemann 2013 [86]	Phase I	10 HSCT	CMV, EBV, AdV post-transplant infections	CMV+EBV+AdV	Allogeneic donor-derived 0.5-2 × 107/m2	6 m 8/10 virological response	1 (G1) skin GvHD
NCT00711035	Leen 2013 [87]	Phase I/II	58 HSCT recipients	Drug-resistant viral infections	CMV+EBV+AdV	Third-party 2 × 107/m2	ORR 95% at 6w median viral load reduction of 97%	8/50 acute GvHD
NCT02108522	Tzannou 2017 [88]	Phase II	38 HSCT recipients, 45 infections	Drug-resistant viral infections	CMV+EBV+AdV+HHV-6	Third-party 2 × 107 partially HLA-matched VSTs/m2	At 6w, 2/2 EBV achieved CR. 16/17 CMV achieved CR or PR, 5/7 AdV achieved CR or PR, 2/3 HHV-6 achieved PR, 16/16 BK achieved clinical benefit	5 (G1-2) GvHD; 1 (G3) GvHD
ACTRN12613000981729	Smith 2018 [89]	Phase I	22 SOTRs (13 Renal, 8 lung, 1 heart)	Ganciclovir-resistant CMV disease	CMV	Autologous 1-2 × 107 cells/m2	11/13 (84.6%) with virologic or clinical improvement	None
NCT01498484 and NCT00002663	Prockop 2019 [90]	Phase II	13 SOTRs and 33 HCST recipients	EBV-PTLD	EBV	Third-party	ORR in 68% of HCT and 54% of SOTRs 2 year survival 57% HSCT and 54% SOT	1 (G1) acute GvHD
NCT02532452 (Cincinnati)	Nelson 2020 [91]	Phase II	41	BK viremia and/or hemorrhagic cystitis or nephropathy after transplant	CMV, EBV, AdV, BK	Allogeneic donor-derived or third-party 5 × 107 VSTs/m2	ORR 86% in BK viremia, 100% ORR in hemorrhagic cystitis; 87% ORR in both	None
NCT02479698	Olson 2021 [92]	Phase II	59 HSCT recipients	BK virus-associated hemorrhagic cystitis	CMV, EBV, BK	third-party 1-2 × 105/kg	CR (34/49) PR (6/49) NR (9/49) at 45d	(G2) skin GvHD, (G3) GI GvHD, 9 chronic GvHD
NCT03883906	Rubinstein 2022 [93]	Phase II	23	Prophylaxis	CMV, EBV, AdV, BK	Allogeneic donor-derived 2 × 107 VST/m2	(7/23) With no viremia; reactivation (11/18); 5 treatment failure	(G2-3) 2/23 GvHD
NCT02532452 (Cincinnati)	Rubinstein 2022 [94]	Phase II	4 HSCT recipients	JCV-Progressive multifocal leukoencephalopathy	CMV, EBV, AdV, BK	Third-party 5 × 107/m2	1/4 stable disease 3/4 progressive disease	None
NCT02108522	Pfeiffer 2023 [95]	Phase II	58 HSCT adult and pediatric recipients	Unresponsive viral infection or antiviral untolerable	CMV + EBV +AdV + BKV + HHV-6 + JCV	Third-party 2 × 107/m2	ORR 95% at 6w	2 (G2 GvHD) and 1 (G3 GvHD)
NCT04605484	Chandraker 2023 [96]	Phase III	61 KTRs	BK viremia	CMV + EBV +AdV + BKV + HHV-6 + JCV	Third-party 4 × 107 cells	50% (10/20) ≥ 1 log BKV viral load reduction (biweekly dosing) 30% (6/20) ≥ 1 log BKV viral load reduction (monthly dosing)	None
NCT02532452 (Cincinnati)	Khoury 2024 [97]	Phase II	98 SOTRs (52 Kidney, 18 Liver, 16 Hear, 8 Lung, 4 small bowel)	refractory viral reactivation/infection	EBV + CMV + AdV + BKV	Third-party 50 × 106 cells/m2.	ORR of 45% for BKV, 65% for CMV, 68% for AdV, and 61% for EBV.	3 episodes of acute organ rejection
NCT04832607	Feuchtinger (TRACE) 2024 [94]	Phase III	HSCT recipients	New or refractory CMV, EBV, or AdV viral infection	CMV + EBV + AdV	Allogeneic donor-derived 1.0 × 105 T cells/ kg recipient (HLA-matched) 2.5 × 104 T cells/ kg (HLA-mismatched)	Ongoing

Abbreviations: SOTRs = solid organ transplant recipients; HSCT = hematopoietic stem cell transplantation; PTLD = post-transplant lymphoproliferative disorder; EBV = Epstein-barr virus; CMV = cytomegalovirus; AdV = Adenovirus; BKV = BK virus; HHV-6 = human-herpes virus-6; JCV = JC virus; ORR = objective response rate; CR = complete response; PR = partial response; NR = no response; HLA = human leukocyte antigen; VST = viral specific therapy; GvHD = graft versus host disease; GI = gastrointestinal