Table 3.
Ongoing or recently completed clinical trials using epigenetic drugs in the treatment of myeloid malignancies. Allo-HSCT, allogeneic hematopoietic stem cell transplantation; AML, acute myeloid leukemia; ATRA, all-trans retinoic acid; CMML, chronic myelomonocytic leukemia; DLBCL, diffuse large B-cell lymphoma; MDS, myeloid dysplastic syndrome; MPN, myeloproliferative neoplasms; R/R, relapsed or refractory; sAML, secondary acute myeloid leukemia.
| Targets/Agents | Drug Name | Diseases | NCT Number | Phase Trial | Combination | Completion Date |
|---|---|---|---|---|---|---|
| HMAs | Azacitidine | IDH1-mutant AML and MDS | NCT03471260 | Phase I/II | Venetoclax and ivosidenib | 2021 |
| TP53-mutant AML and MDS | NCT03588078 | Phase I/II | APR-246 | 2021 | ||
| TP53-mutant MDS | NCT03745716 | Phase III | APR-246 | 2021 | ||
| TP53-mutant myeloid malignancies | NCT04214860 | Phase I | Venetoclax and APR-246 | 2021 | ||
| AML, MDS | NCT02775903 | Phase II | PD-L1 inhibitor durvalumab (MEDI4736) | 2021 | ||
| AML, MDS | NCT03030612 | Phase I/II | Anti-CD70 antibody ARGX-110 | 2021 | ||
| R/R AML, MDS | NCT01869114 | Phase II | mTOR inhibitor sirolimus | 2021 | ||
| Treatment-naïve MDS | NCT02942290 | Phase I | Venetoclax | 2022 | ||
| AML, MDS, CMML | NCT02397720 | Phase II | PD-1 inhibitor nivolumab | 2022 | ||
| AML, MDS | NCT04275518 | Phase I | MDM2 inhibitor APG-115 | 2022 | ||
| AML, MDS | NCT02319369 | Phase I | MDM2 inhibitor milademetan | 2022 | ||
| AML, MDS, CMML | NCT04256317 | Phase II/III | Cytidine deaminase inhibitor ASTX727 | 2023 | ||
| AML, MDS | NCT04609826 | Phase I | Dihydroorotate dehydrogenase inhibitor JNJ-74856665 | 2023 | ||
| AML, MDS | NCT03113643 | Phase I | Venetoclax and SL-401 | 2024 | ||
| AML, MDS, CMML, MPN | NCT03862157 | Phase I/II | Venetoclax and pevonedistat | 2024 | ||
| R/R AML, MDS | NCT04487106 | Phase II | Venetoclax and trametinib | 2024 | ||
| R/R FLT3-mutant AML, R/R MDS, R/R CMML, R/R MPN | NCT04140487 | Phase I/II | Venetoclax and gilteritinib | 2024 | ||
| AML, MDS, CMML | NCT04730258 | Phase I/II | PLK4 inhibitor CFI-400945 | 2024 | ||
| AML, MDS, MPN | NCT04771130 | Phase I/II | BCL2 inhibitor BGB-11417 | 2024 | ||
| AML, MDS with impending relapse | NCT04712942 | Phase II | NEDD8-inhibitor pevonedistat | 2026 | ||
| CC-486 | AML, MDS after allo-HSCT | NCT04173533 | Phase III | 2024 | ||
| Decitabine | AML, MDS | NCT03066648 | Phase I | PD-1 inhibitor PDR001 and checkpoint inhibitor MBG453 | 2021 | |
| Untreated AML or R/R AML | NCT02878785 | Phase I/II | PARP inhibitor talazoparib | 2022 | ||
| AML, MDS, CMML | NCT03306264 | Phase III | Cytidine deaminase inhibitor ASTX727 | 2022 | ||
| AML, MDS, CMML | NCT04730258 | Phase I/II | PLK4 inhibitor CFI-400945 | 2024 | ||
| R/R AML, R/R high-risk MDS | NCT03404193 | Phase II | Venetoclax | 2024 | ||
| R/R AML, MDS | NCT02190695 | Phase II | Carboplatin, arsenic trioxide | 2026 | ||
| Guadecitabine (SGI-110) | AML, MDS, CMML | NCT01261312 | Phase I/II | 2019 | ||
| AML, MDS | NCT03603964 | Phase II | 2021 | |||
| AML and MDS after allo-HSCT | NCT03454984 | Phase II | 2022 | |||
| AML, MDS, CMML | NCT02935361 | Phase I/II | PD-L1 inhibitor atezolizumab | 2021 | ||
| NTX-301 (DNMT1 inhibitor) | AML, MDS, CMML | NCT04167917 | Phase I | 2025 | ||
| BET | Birabresib (OTX015, MK-8628) | AML, sAML, DLBCL | NCT02698189 | Phase I | 2021 | |
| CPI0610 | AML, MDS, MPN | NCT02158858 | Phase I/II | JAK1/2 inhibitor ruxolitinib | 2021 | |
| ABBV-744 | R/R AML | NCT03360006 | Phase I | 2022 | ||
| FT-1101 | R/R AML, MDS, non-Hodgkin’s lymphoma | NCT02543879 | Phase I | Azacitidine | 2019 | |
| PLX2853 | R/R AML, MDS | NCT03787498 | Phase I | 2021 | ||
| PLX51107 | AML, MDS | NCT04022785 | Phase I | 2022 | ||
| HDAC | LBH589 (Panobinostat) | AML, MDS, CMML | NCT00946647 | Phase Ib/IIb | Azacitidine | 2019 |
| High-risk AML and MDS after allo-HSCT | NCT04326764 | Phase III | 2023 | |||
| Vorinostat | AML, MDS | NCT00948064 | Phase II | Azacitidine | 2017 | |
| AML and MDS after allo-HSCT | NCT03843528 | Phase I | Low-dose azacitidine | 2021 | ||
| Belinostat | R/R AML, R/R MDS | NCT03772925 | Phase I | NEDD8-inhibitor pevonedistat | 2021 | |
| IDH1 | Ivosidenib | IDH1-mutant AML and MDS | NCT03503409 | Phase II | 2025 | |
| IDH1-mutant AML | NCT03173248 | Phase III | Azacitidine | 2022 | ||
| BAY1436032 | IDH1-mutant AML | NCT03127735 | Phase I | 2019 | ||
| FT-2102 | IDH1-mutant AML and MDS | NCT02719574 | Phase I/II | Azacitidine or cytarabine | 2020 | |
| IDH305 | IDH1-R132 mutant AML and MDS | NCT02381886 | Phase I | 2022 | ||
| LY3410738 | IDH1- or IDH2-mutant AML, MDS, CMML, MPN | NCT04603001 | Phase I | 2023 | ||
| IDH2 | Enasidenib | IDH2-mutant AML and MDS | NCT03744390 | Phase II | 2023 | |
| IDH2-mutant AML and MDS | NCT03383575 | Phase II | Azacitidine | 2023 | ||
| IDH2-mutant AML, MDS, CMML after allo-HSCT | NCT04522895 | Phase II | 2024 | |||
| EZH2 | Tazemetostat | R/R Non-Hodgkin’s lymphoma | NCT03009344 | Phase I | 2020 | |
| B-cell lymphomas, advanced solid tumors, DLBCL | NCT01897571 | Phase I/II | 2021 | |||
| DOT1L | Pinometostat | R/R AML or AML with MLL-rearrangement | NCT03701295 | Phase I/II | Azacitidine | 2021 |
| AML with MLL-rearrangement | NCT03724084 | Phase I/II | Standard chemotherapy | 2021 | ||
| PRMT5 | GSK3326595 | AML, MDS | NCT03614728 | Phase I | Azacitidine | 2023 |
| JNJ-64619178 | Advanced solid tumors, non-Hodgkin’s lymphoma, low-risk MDS | NCT03573310 | Phase I | 2022 | ||
| PF-06939999 | Advanced or metastatic solid tumors | NCT03854227 | Phase I | 2024 | ||
| LSD1 | Tranylcypromine | AML, MDS | NCT02273102 | Phase I | ATRA | 2020 |
| GSK2879552 | AML, MDS | NCT02177812 | Phase I | ATRA | 2017 | |
| IMG-7289 | AML, MDS | NCT02842827 | Phase I | ATRA | 2018 | |
| INCB059872 | Solid tumors and AML, MDS | NCT02712905 | Phase I/II | ATRA, azacitidinecitidine and nivolumab | 2020 | |
| Seclidemstat (SP-2577) | CMML, MDS | NCT04734990 | Phase I/II | Azacitidine | 2022 | |
| CC-90011 | R/R AML, treatment-naïve AML not eligible for chemotherapy | NCT04748848 | Phase I/II | Venetoclax and azacitidine | 2025 |