Table 2.
Overview of selected clinical trials for combination of epigenetic therapies with conventional chemotherapy in AML treatment.
| Drug combination | Phase | n | Inclusion criteria | Outcomes | Trial registration | Reference |
|---|---|---|---|---|---|---|
| Decitabine + (7 + 3) versus 7 + 3 alone | I | 30 | ND-AML<60 years with less-than-favorable karyotype | CR: 83% | NCT00538876 | Scandura and colleagues92 |
| 5-AZA + (7+3) | I | 6 | ND-AML >60 years | Median OS: 266 days, no dose-limiting toxicity | NCT00915252 | Krug and colleagues95 |
| Decitabine + low-dose idarubicin/cytarabine | I/II | 30 | RR-AML, HR-MDS | CR: 67% | ChiCTR-OPC-15005771. | Ye and colleagues96 |
| 5-AZA + (7+3) versus 7 + 3 alone | II | 214 | ND-AML >60 years | Median OS: 15 months (combination) versus 21 months 5-AZA + (7 + 3) | NCT00915252 | Muller-Tidow and colleagues97 |
| Decitabine + clofarabine + idarubicin + cytarabine; followed by consolidation of decitabine + clofarabine + idarubicin + cytarabine | II | 54 | RR-AML (⩽ salvage 2) <65 years | CR: 48% CR/CRi; 46% proceed to allo-HSCT | NCT01794702 | Jain and colleagues98 |
| vorinostat + idarubicin + cytarabine | II | 75 | HR-MDS, ND-AML <65 years | ORR: 85% (76% CR) | NCT00656617 | Garcia-Manero and colleagues99 |
| Vorinostat + etoposide + cytarabine | I | 21 | RR-AML, RR-ALL, secondary AML, CML in blast crisis | Response rate: concurrent versus sequential schedule in ND-AML (46% versus 14%), RR-AML (15% versus 0%) and MDS (60% versus 0%) | NCT00357305 | Gojo and colleagues100 |
| panobinostat + idarubicin + cytarabine | I/II | 38 | ND-AML >65 years | CR: 64%; median OS: 17 months |
NCT00840346 | Ocio and colleagues101 |
| 7 + 3 versus idarubicin + high-dose cytarabine versus idarubicin + vorinostat | III | 738 | ND-AML <60 years | CR: 75–79% for all groups; better outcomes for 7 + 3 for favorable cytogenetics |
NCT0180233 | Garcia-Manero and colleagues102 |
5-AZA, 5-azacitidine; AML, acute myeloid leukemia; CML, chronic myelogenous leukemia; CR, complete remission; CRi, complete remission with incomplete cell count recovery; HR-MDS, high-risk myelodysplastic syndrome; HSCT, hematopoietic stem cell transplant; NCT, ClinicalTrials.gov identifier; ND, new diagnosis; ORR, overall response rate; OS, overall survival; Ref, reference; RR, relapsed/refractory.