TABLE 2. Treatment detail and adverse events.
| Cohort | Escalation detail | DT2219 dose μg/kg/day | Doses received | Total dose per cycle in μg | N | Drug related adverse effects (CTCAE v4.03 toxicity grade) | DLT |
| 1 | Rapid escalation | 0.5 | 4 | 2.0 | 1 | None | No |
| 2 | 1.25 | 4 | 5.0 | 1 | None | No | |
| 3 | 2.5 | 4 | 10 | 1 | Gr 1 fever (n=1) | No | |
| 4 | Standard escalation | 5.0 | 4 | 20 | 3 | None | No |
| 5 | 10.0 | 4 | 40 | 4a | None | No | |
| 6 | 20.0 | 4 | 80 | 3 | Gr 1 ALT elevation (n=1) Gr 2 ALT, AST elevation (n=1) |
No | |
| 7 | 40.0 | 4b | 160 | 5 | Gr 1 AST, Gr 2 hypoalbuminemia (n=1) Gr 2 capillary leak syndrome (n=2) Gr 1 fatigue (n=1) Gr 2 hypokalemia (n=1) Gr 3 legs weakness (n=1) |
1 | |
| 8 | Continual Reassessment | 60.0 | 4 c,d | 240 | 5 | Gr 1-2 capillary leak syndrome (n=3) Gr 2 anemia (n=1) Gr 3 thrombocytopenia (n=2) Gr 2 fever (n=2) Gr 4 neutropenia (n=1) Gr 3 capillary leak sy (n=1) Gr 3 neutropenic fever (n=1) Gr 2 hearing loss (n=1) Gr 1 hypocalcemia (n=1) |
1 |
| 9 | 80.0 | 4 | 320 | 3 | Gr 1 hypokalemia (n=1) Gr 1-2 capillary leak syndrome (n=2) Gr 1 vomiting (n=1) Gr 3 hypokalemia (n=1) Gr 1 AST ALT elevation (n=2) Gr 2 fatigue (n=2) |
No |
a
1 patient at the 10 μg/kg/day was less than 12 years old and enrolled after receiving permission from the local IRB
b
patient with DLT received 3 doses of DT2219
c
1 patient at the 60 μg/kg/day was retreated 8 weeks later with 2nd cycle at dose 40 μg/kg/day.
d
1 patient was dose reduced for 4th injection to 40 μg/kg/day due to capillary leak syndrome