Table 1.
Patient demographics and baseline characteristics
| Characteristic | Dose-escalation phase | Dose-expansion phase | Dose-escalation + expansion phase | ||
|---|---|---|---|---|---|
| Arm A,VEN + DEC (n = 23) | Arm B,VEN + AZA (n = 22) | Arm D,VEN + DEC (n = 50) | Arm E, VEN + AZA (n = 50) | Total (N = 145)* | |
| Median age (range), y | 74 (68–85) | 75 (65–82) | 73 (65–86) | 74 (65–86) | 74 (65–86) |
| Age >75 y, n (%) | 10 (44) | 9 (41) | 17 (34) | 16 (32) | 52 (36) |
| Sex, n (%) | |||||
| Male | 9 (39) | 11 (50) | 30 (21) | 31 (62) | 81 (64) |
| Female | 14 (61) | 11 (50) | 20 (40) | 19 (38) | 64 (44) |
| ECOG PS, n (%) | |||||
| 0 | 2 (9) | 4 (18) | 12 (24) | 14 (28) | 32 (22) |
| 1 | 17 (74) | 14 (64) | 30 (60) | 29 (58) | 90 (62) |
| 2 | 4 (17) | 4 (18) | 8 (16) | 7 (14) | 23 (16) |
| Cytogenetics, n (%)† | |||||
| Intermediate risk | 15 (65) | 12 (55) | 26 (52) | 21 (42) | 74 (51) |
| Poor risk | 8 (35) | 10 (45) | 24 (48) | 29 (58) | 71 (49) |
| De novo AML, n (%) | 20 (87) | 16 (73) | 39 (76) | 35 (70) | 109 (75) |
| Secondary AML, n (%) | 3 (13) | 6 (27) | 12 (24) | 15 (30) | 36 (25) |
| Mutation, n (%)‡ | |||||
| FLT3§ | 6 (26) | 1 (5) | 6 (12) | 5 (10) | 18 (12) |
| IDH1 or 2‖ | 8 (35) | 7 (32) | 9 (18) | 11 (22) | 35 (24) |
| NPM1 | 9 (39) | 2 (9) | 6 (12) | 6 (12) | 23 (16) |
| TP53 | 3 (13) | 3 (14) | 13 (26) | 17 (34) | 36 (25) |
| Antecedent hematologic disorder, n (%) | 2 (9) | 3 (14) | 9 (18) | 12 (24) | 26 (18) |
| Baseline BM blast count, n (%) | |||||
| <30% | 5 (22) | 6 (27) | 10 (20) | 14 (28) | 35 (24) |
| ≥30% to <50% | 7 (30) | 9 (41) | 22 (44) | 17 (34) | 55 (38) |
| ≥50% | 11 (48) | 7 (32) | 18 (36) | 19 (38) | 55 (38) |
| Hydroxyurea before study initiation, n (%) | 6 (26) | 2 (9) | 4 (8) | 5 (10) | 17 (12) |
| Median time on study (range), months¶ | 7.0 (0.26-31.7) | 5.4 (0.9-30.0) | 11.8 (0.2-16.5) | 9.3 (0.5-16.2) | 8.9 (0.2-31.7) |
Includes 11 patients treated with VEN 1200 mg.
NCCN risk categorization: NCCN Guidelines. Acute myeloid leukemia. Version 2.2014.15
Central laboratory. FLT3, IDH1/2, and TP53 mutational testing results were evaluable for 141/145 patients, with no data available for 1 patient from arm B and 3 patients from arm D.
FLT3-ITD mutations were identified in 10 patients, and FLT3-TKD in 6 patients; 1 patient had both FLT3-ITD and TKD, 1 patient had atypical TKD mutation at S451, and 1 patient had an amplification of FLT3.
IDH1R132 mutations were identified in 15 patients, IDH2R140 in 13 patients, IDH2R172 in 6 patients, and 1 patient in a nonhotspot mutation in IDH2K282.
The median time on study was calculated from the time of first dose of study drug to either the cutoff date (for active patients) or the date a patient discontinued the study.