Table 1.
Completed clinical trials with results involving adoptive Treg therapy in GVHD (search date March 30, 2022).
| Treg type | Study ID | Patients | HSC product | Cell Product | Dose | Outcomes | Center | Ref’s. |
|---|---|---|---|---|---|---|---|---|
| Fresh Treg |
2012-002685-12 | 9 | Not specified | Fresh PB CD4 Treg Up to 5×106/kg | Fresh CD4 tTreg Up to 5×106/kg × once |
Safe; not designed for efficacy | University Hospital Regensburg, Germany | (41) |
| 01/08 | 28 | Haploidentical | Fresh PB CD4 Tregs and Tcons | 2×106/kg - 4×106/kg Treg and 0.5×106/kg - 2×106/kg Tcon | 15% developed ≥ grade 2 aGVHD 5% developed relapse |
University of Perugia, Italy | (42, 43) | |
| NCT01660607 | 24 | TCD MRD/MUD | Fresh PB CD4 Tregs and Tcons | 1×106/kg - 3×106/kg Treg and 1×105/kg - 3×107/kg Tcon | 1st cohort: 40% ≥ grade 2 aGVHD 2nd cohort: No GVHD (n = 7) |
Stanford, USA | (44) | |
| NCT02423915 | 5 | dUCBT, n = 2 PB MUD, n = 3 |
fresh UCB CD4 Treg ± Fucosylation | 1.2×106/kg | 100% ≥ grade 2 aGVHD | MD Anderson, USA | (45) | |
| Expanded Treg |
NKEBN/458-310/2008 | 2 | MRD | Expanded CD4 Treg | 3 × 106/kg in SR aGVHD | Reduced IST in cGVHD. Only transient improvement in aGVHD | Medical University of Gdańsk, Poland | (46) |
| NCT00602693 | 23 | dUCBT | Expanded UCB CD4 Treg | 0.01-3×106/kg Treg | 43% ≥ grade 2 aGVHD (vs. 61% in hist. control) |
University of Minnesota, USA | (4) | |
| NCT00602693 | 11 | dUCBT | Expanded UCB CD4 Treg | 3×106-1×108/kg Treg | 9% developed ≥ grade 2 aGVHD | University of Minnesota, USA | (5) | |
| EK 206082008 | 5 | Any | Expanded PB CD4 Treg | 5×105/kg – 4.4×106/kg × once | Clinical response to SR-cGVHD in 2 pts. Stable disease in 3 pts |
University Hospital Carl Gustav Carus, Germany | (47) | |
| 3 | Any | Expanded donor PB CD4 Treg | 3×106/kg Treg | Clinical response to SR-cGVHD in 3 pts. | Charité – Universitätsmedizin Berlin, Germany | (48) | ||
| iTreg | NCT01634217 | 14 | MRD | Expanded PB CD4 iTregs | Up to 3×108/kg | 2nd cohort: 20% ≥ grade 2 aGVHD | University of Minnesota, USA | (7) |
| Tr1 | ALT-TEN | 18 | Haplo | Expanded IL-10 Tr1 DLI | 1-3x105 CD3C T cells/kg | Grade 3 GVHD in 1/5 pts with immune reconstitution. No GVHD in 7 pts without immune reconstitution |
San Raffaele University, Italy | (49) |
| NCT03198234 | Any | Expanded T-allo10 cells | 1-9x106-T-allo10/kg | Tr1 cells detected up to 1 yr after HSCT. Cont. recruitment. | Stanford, USA | (50) |
HSCT, hematopoietic stem cell transplantation; cGVHD, chronic GVHD; GVHD, graft-verus-host disease; aGVHD, acute GVHD; MRD, matched related donor; MUD, matched unrelated donor; TAC, tacrolimus; CSA, cyclosporin; Siro, sirolimus; IST, immunosuppressive therapy; SR GVHD, steroid-refractory GVHD; dUCBT, double umbilical cord blood transplant; MMF, mycophenolate mofetil; PB, peripheral blood; UCB, umbilical cord blood.