Table 1.
Selected phase II and III clinical trials of DNMT inhibitors in AML
| Study | Design | Participants | N | Responses | Median Overall survival (OS) |
Ref |
|---|---|---|---|---|---|---|
| Azacitidine(AZ A-001) |
Randomized phase III |
Reclassification of AML based on WHO criteria, Bone marrow (BM) blast 20~30% |
55 | 18% CR | 24.5ms (Aza) vs 16 ms (CCR) (p=0.005) |
47 |
| Azacitidine(CAL BG 8421, 8921, 9221) |
Randomized phase III |
Reclassification of AML based on WHO criteria, BM blast 20~30% |
103 | 35~48% (CR/PR/HI) |
19.3 ms (Aza) vs 12.9 ms (observation) (only from CALGB 9221) (p value not indicated) |
48 |
| Decitabine(DA CO-017) |
Single arm phase II |
AML with age>60, intermediate/poor risk (de novo or secondary) |
55 | 25% (CR/PR) | 7.7 ms | 49 |
| Decitabine (00332/AMLSG 14-09) |
Single arm phase II |
AML with age>60, intermediate/poor risk (de novo or secondary) |
277 | 26% (CR/PR) | 5.5 ms | 50 |
| Decitabine(DA CO-016) |
Randomized phase III |
AML with age>65, intermediate/poor risk (de novo or secondary) |
242 | 17.8% (CR+CRi) (vs. 7.8% treatment choice, p=0.001) |
7.7 ms (decitabine) vs 5.0 ms (treatment choice) (p=0.0373) |
51 |
Pts: patients
CR (complete remission): the disappearance of all signs and symptoms related to the disease, a bone marrow with 5% or fewer blasts and peripheral blood count with an absolute neutrophil count of 109/L or more and platelet count of 100 × 109/L or more.
CRp: CR except for a platelet count increase by 50% to more than 30 × 109/L but less than 100 × 109/L.
PR (Partial remission): A cellular marrow aspirate with 5% to 25% blasts, with a platelet count greater than 100×109/L and WBC less than 1.5×109/L
Bone marrow (BM) response: bone marrow blast of 5% or less but without meeting the peripheral blood count criteria for CR or CRp.
Hematologic improvement (HI): HI-E: a hemoglobin increase by at least 15g/L or transfusion independence, HI-P: an absolute increase of platelet counts from less than 20 to more than 20 × 109/L and by at least 100% or if more than 20 × 109/L, by an absolute increase of at least 30 × 109/L, HI-N: a granulocyte increase by at least 100% and by an absolute increase of at least 0.5 × 109/L.
CCR: conventional care regimen
N: number of patients
Aza: azacitidine