Table 3.
Dose levels and dose limiting toxicities (DLTs)
| DSI Schedule
| |||||
|---|---|---|---|---|---|
| Dose level | Vorinostat (mg total dose) orally, TID Days 1–14 | Alvocidib loading dose | Alvocidib (mg/m2) 1-h intravenous infusion days 1–5 | Patients treated/DLT | DLT |
| 1 | 200 | ---- | 10 | 4/0 | |
| 2 | 200 | ---- | 20 | 3/0 | |
| 3 | 200 | ---- | 30 | 4/0 | |
| 4 | 200 | ---- | 40 | 3/1 | Gr 4 infection with neutropenia (sepsis >7d) |
| WLMI Schedule
| |||||
|---|---|---|---|---|---|
| Dose level | Vorinostat (mg total dose) orally, TID Days 1–14 | Alvocidib (mg/m2) 30-min intravenous loading dose days 1, 8 | Alvocidib (mg/m2) 4-h intravenous infusion days 1, 8 | Patients treated/DLT | DLT |
| 5* | 200 | 20 | 20 | 7/0 | |
| 6A† | 200 | 30 | 20 | 1/NE†† | |
| 6B** | 200 | 30 | 30 | 6/2 | Gr 3 atrial fibrillation Gr 3 QTc prolongation (intermittent, precluded vorinostat dosing for >7d) |
*
Defined as the MTD.
**
Exceeded the MTD.
†
Level defined by clerical error in study protocol and was aborted after 1 patient enrolled.
††
Patient did not complete cycle 1 of treatment so not evaluable (NE) for DLT.