Combined epigenetic targeting agents with other small molecules
| Drug . | Disease type . | NCT no. . | Enrollment status . | Response data . | Grade 3/4 toxicity . |
|---|---|---|---|---|---|
| Proteasome inhibitor: bortezomib | |||||
| Azacitidine | PTCL | 01129180 | Completed | ||
| Vorinostat | Maintenance after ASCT | 00992446 | Completed | ||
| Vorinostat | MCL and DLBCL | 00703664 | Completed; phase 2, N = 65 | ORR, 10%; terminated early poor accrual | Thrombocytopenia, lymphopenia, diarrhea |
| Belinostat | HL and NHL | 00348985 | Completed; phase 1, | Anorexia, dehydration, fatigue | |
| N = 22 | |||||
| Panobinostat | PTCL | 00901147 | Completed; phase 2, | CR, 22%; ORR, 43% | Thrombocytopenia, neutropenia, diarrhea |
| N = 25 | |||||
| Panobinostat | MCL | 01504776 | Completed | ||
| Proteasome inhibitor: carfilzomib | |||||
| Romidepsin | PTCL | 03141203 | Active, not recruiting | ||
| Belinostat | NHL | 02142530 | Completed | ||
| Vorinostat | NHL | 01276717 | Completed; phase 1, | ORR, 5% | Toxicities led to dose reductions to dose level −1 |
| N = 20 | |||||
| Proteasome inhibitor: ixazomib | |||||
| Romidepsin | PTCL | 03547700 | Recruiting | ||
| DNMT/HDAC: azacitidine | |||||
| Vorinostat | NK/TCL | 00336063 | Active, not recruiting | ||
| Vorinostat | DLBCL | 01120834 | Completed; phase 1b, | ORR, 6.7%; 3-mo OS, 77% | Thromboembolism, diarrhea |
| N = 18 | |||||
| Romidepsin | HL and NHL | 01998035 | Active, not recruiting; phase 1/2; phase 1, N = 33 | ORR, 32%; in PTCL: ORR, 73%; CR, 55% | Thrombocytopenia, leukopenia, lung infection |
| Mocetinostat | HL and NHL | 05433582 | Terminated | ||
| DNMT/HDAC: decitabine | |||||
| Vorinostat | HL and NHL | 00275080 | Completed; phase 1, | ORR, 0% | Neutropenia, thrombocytopenia |
| N = 43 | |||||
| Chidamide | Relapse after CAR-T | 04337606 | Recruiting | ||
| IMID: lenalidomide | |||||
| Azacitidine | FL/MZL | 01121757 | Terminated | ||
| Panobinostat | HL | 01460940 | Completed; phase 1/2; N = 24 | ORR, 17%; PFS, 3.8 mo | Neutropenia, thrombocytopenia |
| Romidepsin + carfilzomib | NHL | 02341014 | Active, not recruiting; phase 1b/2, N = 27 | In TCL at MTD; CR, 36%; ORR, 45% | Neutropenia, thrombocytopenia |
| Tazemetostat + rituximab | FL | 04224493 | Recruiting | ||
| PI3K: tenalisib | |||||
| Romidepsin | PTCL | 00377000 | Recruiting | ||
| PI3K: duvelisib | |||||
| Romidepsin | PTCL | 02783625 | Recruiting; phase 1, N = 39 | ORR, 51%; in PTCL: ORR, 55%; CR, 27% | Increased AST/ALT, neutropenia, hyponatremia |
| BET inhibitor: FT-1101 | |||||
| Azacitidine | HL and NHL | 02543879 | Completed | ||
| BET inhibitor: molibresib besylate | |||||
| Entinostat | HL and NHL | 03925428 | Not yet recruiting | ||
| MTOR: everolimus | |||||
| Panobinostat | HL and NHL | 00967044 | Completed; phase 1, N = 30 | ORR, 43%; CR, 15% | Thrombocytopenia, neutropenia, anemia |
| ADC CD30: brentuximab | |||||
| Romidepsin | CTCL | 02616965 | Recruiting | ||
| Anti-folate: pralatrexate | |||||
| Romidepsin | NHL | 01947140 | Recruiting; phase 1/2; Ph 1, N = 29 | ORR, 57%; in PTCL: ORR, 71%; CR, 17% | Anemia, mucositis, thrombocytopenia |
| Aurora A kinase inhibitor: alisertib | |||||
| Romidepsin | NHL | 01897012 | Completed; phase 1, N = 25 | ORR, 28%; CR, 12% | Thrombocytopenia, anemia, infection |
| Retinoid: isotretinoin | |||||
| Entinostat | HL and NHL | 00098891 | Completed | ||
| Sirtuin inhibitor: niacinamide | |||||
| Vorinostat | HL and NHL | 00691210 | Completed; phase 1, N = 28 | ORR, 24%; SD, 57% | Thrombocytopenia, infection |
| Drug . | Disease type . | NCT no. . | Enrollment status . | Response data . | Grade 3/4 toxicity . |
|---|---|---|---|---|---|
| Proteasome inhibitor: bortezomib | |||||
| Azacitidine | PTCL | 01129180 | Completed | ||
| Vorinostat | Maintenance after ASCT | 00992446 | Completed | ||
| Vorinostat | MCL and DLBCL | 00703664 | Completed; phase 2, N = 65 | ORR, 10%; terminated early poor accrual | Thrombocytopenia, lymphopenia, diarrhea |
| Belinostat | HL and NHL | 00348985 | Completed; phase 1, | Anorexia, dehydration, fatigue | |
| N = 22 | |||||
| Panobinostat | PTCL | 00901147 | Completed; phase 2, | CR, 22%; ORR, 43% | Thrombocytopenia, neutropenia, diarrhea |
| N = 25 | |||||
| Panobinostat | MCL | 01504776 | Completed | ||
| Proteasome inhibitor: carfilzomib | |||||
| Romidepsin | PTCL | 03141203 | Active, not recruiting | ||
| Belinostat | NHL | 02142530 | Completed | ||
| Vorinostat | NHL | 01276717 | Completed; phase 1, | ORR, 5% | Toxicities led to dose reductions to dose level −1 |
| N = 20 | |||||
| Proteasome inhibitor: ixazomib | |||||
| Romidepsin | PTCL | 03547700 | Recruiting | ||
| DNMT/HDAC: azacitidine | |||||
| Vorinostat | NK/TCL | 00336063 | Active, not recruiting | ||
| Vorinostat | DLBCL | 01120834 | Completed; phase 1b, | ORR, 6.7%; 3-mo OS, 77% | Thromboembolism, diarrhea |
| N = 18 | |||||
| Romidepsin | HL and NHL | 01998035 | Active, not recruiting; phase 1/2; phase 1, N = 33 | ORR, 32%; in PTCL: ORR, 73%; CR, 55% | Thrombocytopenia, leukopenia, lung infection |
| Mocetinostat | HL and NHL | 05433582 | Terminated | ||
| DNMT/HDAC: decitabine | |||||
| Vorinostat | HL and NHL | 00275080 | Completed; phase 1, | ORR, 0% | Neutropenia, thrombocytopenia |
| N = 43 | |||||
| Chidamide | Relapse after CAR-T | 04337606 | Recruiting | ||
| IMID: lenalidomide | |||||
| Azacitidine | FL/MZL | 01121757 | Terminated | ||
| Panobinostat | HL | 01460940 | Completed; phase 1/2; N = 24 | ORR, 17%; PFS, 3.8 mo | Neutropenia, thrombocytopenia |
| Romidepsin + carfilzomib | NHL | 02341014 | Active, not recruiting; phase 1b/2, N = 27 | In TCL at MTD; CR, 36%; ORR, 45% | Neutropenia, thrombocytopenia |
| Tazemetostat + rituximab | FL | 04224493 | Recruiting | ||
| PI3K: tenalisib | |||||
| Romidepsin | PTCL | 00377000 | Recruiting | ||
| PI3K: duvelisib | |||||
| Romidepsin | PTCL | 02783625 | Recruiting; phase 1, N = 39 | ORR, 51%; in PTCL: ORR, 55%; CR, 27% | Increased AST/ALT, neutropenia, hyponatremia |
| BET inhibitor: FT-1101 | |||||
| Azacitidine | HL and NHL | 02543879 | Completed | ||
| BET inhibitor: molibresib besylate | |||||
| Entinostat | HL and NHL | 03925428 | Not yet recruiting | ||
| MTOR: everolimus | |||||
| Panobinostat | HL and NHL | 00967044 | Completed; phase 1, N = 30 | ORR, 43%; CR, 15% | Thrombocytopenia, neutropenia, anemia |
| ADC CD30: brentuximab | |||||
| Romidepsin | CTCL | 02616965 | Recruiting | ||
| Anti-folate: pralatrexate | |||||
| Romidepsin | NHL | 01947140 | Recruiting; phase 1/2; Ph 1, N = 29 | ORR, 57%; in PTCL: ORR, 71%; CR, 17% | Anemia, mucositis, thrombocytopenia |
| Aurora A kinase inhibitor: alisertib | |||||
| Romidepsin | NHL | 01897012 | Completed; phase 1, N = 25 | ORR, 28%; CR, 12% | Thrombocytopenia, anemia, infection |
| Retinoid: isotretinoin | |||||
| Entinostat | HL and NHL | 00098891 | Completed | ||
| Sirtuin inhibitor: niacinamide | |||||
| Vorinostat | HL and NHL | 00691210 | Completed; phase 1, N = 28 | ORR, 24%; SD, 57% | Thrombocytopenia, infection |
ADC, antibody drug conjugate; ALT, alanine aminotransferase; ASCT, autologous stem cell transplant; AST, aspartate transaminase; BET, bromodomain and extraterminal motif; CAR-T, chimeric antigen receptor T cell; CR, complete response; IMID, immune-modulatory drug; MCL, mantle cell lymphoma; MTD, maximum tolerated dose; MTOR, mammalian target of rapamycin; MZL, marginal zone lymphoma; NHL, non-Hodgkin lymphoma; NK, natural killer; OS, overall survival; PFS, progression-free survival; TCL, T-cell lymphoma. See Tables 1 and 2 for expansion of other abbreviations.