Table 1.
Summary of clinical trials for novel agents targeting leukemia cells or immune microenvironment following allo-HSCT.
| Target | Agent | Intervention strategy | Therapy regimen | Identifier (phase) | Status | Complete date | With results |
|---|---|---|---|---|---|---|---|
| Oncogenic effectors | |||||||
| FLT3 | Sorafenib | Salvage | +/−DLI | NCT02867891 (no) | Completed | 12/2016 | Yes |
| Maintenance | Mono | NCT01398501 (1) | Completed | 8/2016 | Yes | ||
| Maintenance | Mono | NCT02474290 (2/3) | Completed | 8/2019 | Yes | ||
| Maintenance | Mono | NCT01578109 (no) | Active, not recruiting | 12/2025 | Yes | ||
| Maintenance | Mono | NCT03247088 (1/2) | Recruiting | 7/2022 | No | ||
| Midostaurin | Preemptive | Mono | NCT03951961 (2) | Not yet Recruiting | 12/2023 | No | |
| Maintenance | Mono | NCT01477606 (2) | Active, not recruiting | 6/2020 | Yes | ||
| Maintenance | Mono | NCT01883362 (2) | Completed | 4/2018 | No | ||
| Quizartinib | Salvage/maintenance | Mono | NCT02039726 (3) | Active, not recruiting | 12/2020 | Yes | |
| Maintenance/preemptive | Mono | NCT01468467 (1) | completed | 3/2015 | Yes | ||
| Gliteritinib | Maintenance | Mono | NCT02997202 (3) | Recruiting | 4/2025 | No | |
| Crenolanib | Maintenance | Mono | NCT02400255 (2) | Recruiting | 6/2021 | No | |
| BCL-2 | Venetolax | Maintenance/preemptive | +AZA | NCT04161885 (3) | Recruiting | 8/2024 | No |
| Maintenance/preemptive | +AZA | NCT04128501 (2) | Not yet Recruiting | 10/2022 | No | ||
| IDH1 | Ivosidenib | Maintenance | Mono | NCT03564821 (1) | Recruiting | 7/2024 | No |
| IDH2 | Enasidenib | Maintenance | Mono | NCT03515512 (1) | Recruiting | 5/2024 | No |
| Maintenance | Mono | NCT03728335 (1) | Recruiting | 12/2020 | No | ||
| SMO | Glasdegib | Maintenance | Mono | NCT04168502 (3) | Not yet Recruiting | 12/2026 | No |
| Key metabolism | |||||||
| DNA methylation | Azacitidine | Salvage | Mono | NCT01083706 (2) | Completed | 12/2013 | Yes |
| Salvage | Mono | NCT02017457 (2) | Completed | 11/2019 | Yes | ||
| Salvage | Mono | NCT00422890 (3) | Completed | 12/2009 | Yes | ||
| Salvage | +DLI | NCT00795548 (2) | Completed | 8/2011 | Yes | ||
| Salvage | +IFN | NCT04078399 (no) | Recruiting | 5/2020 | No | ||
| Salvage | +Chemo + DLI | NCT01390311 (1) | Completed | 4/2015 | Yes | ||
| Salvage | +LEN | ISCRCTN98163167 (1) | Completed | 12/2018 | Yes | ||
| Salvage | +LEN + DLI | NCT02472691 (2) | Active, not recruiting | 9/2020 | No | ||
| Salvage | +Chemo + DLI | NCT01369368 (1/2) | Recruiting | 10/2020 | No | ||
| Preemptive | Mono | NCT01462578 (2) | Active, not recruiting | 8/2020 | Yes | ||
| Preemptive | Mono | NCT03850418 (2) | Recruiting | 2/2024 | No | ||
| Preemptive | +DLI | NCT01541280 (2) | Completed | 7/2015 | Yes | ||
| Maintenance/preemptive | +/-DLI | NCT02458235 (2) | Active, not recruiting | 4/2020 | No | ||
| Maintenance | Mono | NCT01995578 (2) | Recruiting | 11/2021 | No | ||
| Maintenance | Mono | NCT00350818 (1) | completed | 8/2010 | No | ||
| Maintenance | Mono | NCT00887068 (3) | completed | 8/2018 | No | ||
| Maintenance | +Nivolumab | NCT04128020 (1) | Recruiting | 10/2022 | No | ||
| Maintenance | +APR-246 | NCT03931291 (2) | Recruiting | 9/2021 | No | ||
| Maintenance | +Valproic Acid | NCT02124174 (2) | Recruiting | 1/2021 | No | ||
| Maintenance | Mono | NCT01168219 (2) | Active, not recruiting | 11/2015 | Yes | ||
| Decitabine | Salvage | +DLI | NCT01758367 (1/2) | Unknown | 6/2018 | Yes | |
| Salvage | +2nd HSCT | NCT00002832 (1/2) | Completed | 3/2002 | No | ||
| Salvage | +Ruxolitinib + DLI | NCT04055844 (2) | Recruiting | 1/2025 | No | ||
| Preemptive | Mono | NCT03663751 (2) | Recruiting | 3/2021 | No | ||
| Preemptive | +DLI | NCT03662087 (2/3) | Recruiting | 12/2022 | No | ||
| Maintenance | Mono | NCT01809392 (2/3) | Unknown | 12/2015 | No | ||
| Maintenance | Mono | NCT01277484 (1) | Unknown | 12/2015 | Yes | ||
| Maintenance | Mono | NCT00986804 (1) | Completed | 2/2016 | Yes | ||
| Maintenance | +DLI | NCT03771222 (2) | Not yet Recruiting | 12/2021 | No | ||
| Guadecitabine | Salvage/preemptive | +DLI | NCT02684162 (2) | Recruiting | 6/2021 | No | |
| Maintenance | Mono | NCT03454984 (2) | Not yet Recruiting | 3/2022 | No | ||
| CC-486 | Maintenance | Mono | NCT01835587 (1/2) | Completed | 5/2017 | Yes | |
| Maintenance | Mono | NCT04173533 (3) | Recruiting | 6/2024 | No | ||
| Histone deacetylases | Panobinostat | Maintenance | Mono | NCT01451268 (1/2) | Unknown | 4/2018 | Yes |
| Maintenance | Mono | NCT04326764 (3) | Recruiting | 10/2023 | No | ||
| Vorinostat | Maintenance | +AZA | NCT03843528 (1) | Recruiting | 12/2021 | No | |
| Epitopes | |||||||
| CD33 | BI 836858 | Salvage | +F16IL2 | NCT03207191 (1) | Unknown | 12/2019 | No |
| GO | Salvage | Mono | NCT00044733 (2) | Completed | 9/2004 | Yes | |
| Maintenance | Mono | NCT01020539 (1) | Active, not recruiting | 12/2020 | No | ||
| Maintenance | Mono | NCT02117297 (2) | Recruiting | 12/2022 | No | ||
| 33 A | Maintenance | Mono | NCT02614560 (1/2) | Terminated | 9/2017 | No | |
| CD38 | Daratumumab | Salvage | +DLI | NCT03537599 (1/2) | Recruiting | 9/2021 | No |
| WT1 | DC vaccine | Salvage/preemptive | +DLI | NCT00923910 (1/2) | Completed | 11/2016 | Yes |
| Preemptive | +DEC | NCT01483274 (1) | Completed | 6/2015 | No | ||
| WT1-sensitized T | Maintenance/preemptive/salvage | +/−(FLU + CTX) | NCT01640301 (1/2) | Active, not recruiting | 10/2030 | Yes | |
| Salvage/preemptive | Mono | NCT00620633 (1) | Active, not recruiting | 2/2021 | No | ||
| CTL | Salvage/preemptive | Mono | NCT00052520 (1/2) | Completed | 6/2013 | No | |
| Maintenance | Mono | NCT02895412 (1) | Recruiting | 12/2020 | No | ||
| CD123 | Anti-CD123-CART | Salvage | Mono | NCT03114670 (1) | Recruiting | 3/2021 | No |
| Immune microenvironment | |||||||
| CTLA-4 | Ipilimumab | Salvage | +DLI | NCT00060372 (1) | Completed | 4/2008 | Yes |
| Salvage | Or Nivolumab | NCT01822509 (1) | Active, not recruiting | 12/2018 | Yes | ||
| Salvage | +LEN | NCT01919619 (2) | Recruiting | 6/2021 | No | ||
| Maintenance | +/-Nivolumab | NCT02846376 (1) | Recruiting | 7/2023 | No | ||
| PD-1 | Nivolumab | Salvage | Mono | NCT03146468 (2) | Recruiting | 6/2020 | No |
| Salvage | +/-Ipilimumab | NCT03600155 (1) | Recruiting | 6/2022 | No | ||
| Salvage | +Tocilizumab | NCT03588936 (1) | Recruiting | 8/2022 | No | ||
| Maintenance | Mono | NCT02985554 (1) | Recruiting | 3/2022 | No | ||
| Maintenance | Mono | NCT04361058 (1) | Recruiting | 4/2025 | No | ||
| Pembrolizumab | Salvage | Mono | NCT02981914 (1) | Recruiting | 2/2029 | No | |
| Salvage | Mono | NCT03286114 (1) | Recruiting | 10/2021 | No | ||
| Engineering donor T | CD25hi Treg depleted | Salvage | Mono | NCT00675831 (1) | Completed | 1/2013 | Yes |
| Salvage | +Ipilimumab | NCT03912064 (1) | Recruiting | 5/2024 | No | ||
| CD8+CD44hi | Salvage | Mono | NCT01523223 (1) | Completed | 10/2016 | Yes | |
| CD45RA-delepted | Maintenance | Mono | NCT03849651 (2) | Recruiting | 7/2025 | No | |
| Engineering donor NK | Purified NK | Salvage | +FLU + Ara-C or DEC | NCT04220684 (1) | Not yet Recruiting | 12/2021 | No |
| Salvage | +CTX + FLU | NCT00526292 (2) | Completed | 7/2015 | Yes | ||
| Maintenance | Mono | NCT00569283 (1) | Completed | 12/2008 | Yes | ||
| Maintenance | Mono | NCT01795378 (1/2) | Completed | 5/2015 | Yes | ||
| Maintenance | Mono | NCT00823524 (1/2) | Completed | 2/2013 | Yes | ||
| Maintenance | Mono | NCT03300492 (1/2) | Recruiting | 1/2023 | No | ||
| Maintenance | Mono | NCT04166929 (2) | Recruiting | 1/2022 | No | ||
| Maintenance | Mono | NCT02727803 (2) | Recruiting | 5/2021 | No | ||
| Maintenance | Mono | NCT01904136 (1/2) | Recruiting | 4/2021 | No | ||
| CD4- iNKT | Maintenance | Mono | NCT03605953 (no) | Not yet Recruiting | 4/2021 | No | |
| CIML NK | Salvage | Chemo + DLI+ | NCT03068819 (1) | Recruiting | 11/2024 | No | |
| Maintenance | +ALT-803 | NCT02782546 (2) | Recruiting | 2/2022 | No | ||
| DC | DC/AML fusion cells | Maintenance | +DEC | NCT03679650 (1) | Recruiting | 8/2024 | No |
| MiHA-loaded PD-L-silenced DC | Maintenance/preemptive | Mono | NCT02528682 (1/2) | Recruiting | 12/2020 | No | |
| CIK | IL-15 activated CIK | Preemptive | Mono | NCT02752243 (1/2) | Recruiting | 3/2022 | No |
| Maintenance | Mono | NCT03669172 (1/2) | Recruiting | 11/2021 | No | ||
| IL-15 | ALT-803 | Salvage | Mono | NCT01885897 (1/2) | Active, not recruiting | 6/2020 | Yes |
| N-803 | Maintenance | Mono | NCT02989844 (2) | Suspended (COVID-19) | 1/2022 | No | |
Complete date, actual or estimated study completion date; Salvage, salvage therapy for patients with hematological relapse; Maintenance, preventive therapy for high-risk patients without any sigh of underlying disease; Preemptive, preemptive therapy for patients with minimal residual disease; Mono, monotherapy; +/−, the clinical trial has two arms, monotherapy or in combination with other regimens; DLI, donor lymphocyte infusion; AZA, azacytidine; IFN, interferon; Chemo, chemotherapy; LEN, lenalidomide; APR-246, agent targeted TP53; 2nd HSCT, the second allo-HSCT; CC-486, oral azacytidine; BI 836858, a human anti-CD33 antibody; F16IL2, F16 antibody fused to human IL-2; GO, gemtuzumab ozogamicin; 33 A, vadastuximab talirine; DEC, decitabine; WT1-sensitized T, WT1-sensitized allogeneic T-lymphocytes; CTL, donor CD8+cytotoxic T lymphocyte clones specific for WT1; Tocilizumab, interleukin-6 receptor antagonist; FLU, fludarabine; Ara-C, cytarabine; CTX, Cyclophosphamide; iNKT, invariant NKT cells; CIML NK, cytokine-induced memory-like (CIML) natural killer cell; DC, dendritic cells; CIK, cytokine induced killer cells; ALT-803 or N-803, interleukin-15 (IL-15) super agonist complex; No, results unavailable.