Table 2.
(Pre)Clinical status of current DNA methylation‐related drugs in combination with other epigenetic therapies or chemoimmunotherapy. BP, blast phase; CR: complete remission; DHFR, dihydrofolate reductase; G‐CSF: granulocyte colony‐stimulating factor; RR, refractory/relapse; TK, tyrosine kinase.
| Drug | Target | Target domains | Condition | Current clinical status | NTC number | Reference |
|---|---|---|---|---|---|---|
| AZA + belinostat | DNMT/HDAC | DNA methylation/histone deacetylation | AML | Completed | NCT00351975 | – |
| AZA + entinostat | DNMT/HDAC | DNA methylation/histone deacetylation | AMLMDS | Phase II, completed | NCT00313586 | [161] |
| AZA + entinostat | DNMT/HDAC | DNA methylation/histone deacetylation | AML (old) | Phase II, recruiting | NCT01305499 | – |
| AZA + homoharringtonine | DNMT/TET | DNA methylation/DNA demethylation | AML | Phase III, recruiting | NCT04248595 | – |
| AZA + pinometostat | DNMT/DOTL1 | DNA methylation/histone methylation | AML | recruiting | NCT03701295 | – |
| AZA + pracinostat | DNMT/HDAC | DNA methylation/histone methylation | AML | Phase II, completed | NCT01912274 | [162] |
| AZA + vorinostat + gemtuzumab ozogamicin | DNMT/HDAC/CD33 | DNA methylation/histone methylation/Leukemic cell marker | AML | Phase I/Phase II, completed | NCT00895934 | [163] |
| ASTX727 + FT‐2102 | DNMT/IDH‐1 | DNA methylation/cell metabolism |
RR‐MDS RR‐AML |
Phase I/Phase II, recruiting | NCT04013880 | – |
| Decitabine + LBH589 | DNMT/HDAC | DNA methylation/histone deacetylation |
AML MDS |
Phase I/Phase II, completed | NCT00691938 | [164] |
| Decitabine + vorinostat | DNMT/HDAC | DNA methylation/histone methylation |
RR‐AML AML MDS |
Phase I, completed | NCT00479232 | [165] |
| Decitabine + vorinostat | DNMT/HDAC | DNA methylation/histone deacetylation | RR‐AML | Phase II, terminated | NCT00882206 | [166] |
| Decitabine + vorinostat + filgrastim + fludarabine + cytarabine | DNMT/HDAC/G‐CSF/DNA and RNA polymerases | DNA methylation/histone deacetylation/Neutrophil growth/DNA synthesis | RR‐AML | Phase I, recruiting | NCT03263936 | – |
| Decitabine + vorinostat + filgrastim + fludarabine + cytarabine + sorafenib | DNMT/HDAC/G‐CSF/DNA and RNA polymerases/TK | DNA methylation/histone deacetylation/Neutrophil growth/DNA synthesis | RR‐AML | Phase I, terminated | NCT02412475 | – |
| Decitabine + vorinostat + vincristine + dexamethasone + mitoxantrone + pegaspargase + methotrexate | DNMT/HDAC/tubulin/glucocorticoid receptor/topoisomerase type II/DHFR | DNA methylation/histone deacetylation/Cell division/DNA synthesis and repair/cell metabolism | ALL | Phase I/Phase II, terminated | NCT01483690 | [167] |
| NTX‐301 | DNMT1 | DNA methylation |
AML MDS |
Phase I, not yet recruiting | NCT04167917 | – |
| Decitabine + nivolumab + CDX‐1401 | DNMT/PD‐1/DEC‐205 | DNA methylation/Immune presentation |
AML MDS |
Phase I, active (not recruiting) | NCT03358719 | – |
| AZA + nivolumab + ipilimumab | DNMT/PD‐1/CTLA4 | DNA methylation/Immune presentation | RR‐AML | Phase II, recruiting | NCT02397720 | – |
| Decitabine + nivolumab + venetoclax | DNMT/PD‐1/BCL‐2 | DNA methylation/Immune presentation/apoptosis | AML | Phase I, recruiting | NCT04277442 | – |
| Guadecitabine + atezolizumab | DNMT/PD‐L1 | DNA methylation/Immune presentation |
AML MDS CMML |
Phase I/Phase II, recruiting | NCT02935361 | – |
| AZA + lenalidomide | DNMT/IKAROS | DNA methylation/Immune response | CR‐AML | Phase II, completed | NCT01301820 | [168] |
| AZA + lenalidomide | DNMT/IKAROS | DNA methylation/Immune response | RR‐AML | Phase II, completed | NCT01743859 | [169] |