Table 3.
Dose Levels and DLTs
| Dose Level | Bortezomib (mg/m2) | Alvocidib (mg/m2) | Patients treated/# DLTs | DLT |
|---|---|---|---|---|
| 1 | 1.0 | 15 | 3/0 | |
| 2 | 1.3 | 15 | 5/0 | |
| 3 | 1.3 | 22 | 3/0 | |
| 4 | 1.3 | 30 | 3/0 | |
| 5a | 1.3 | 40 | 7/1 | Grade 3 back pain |
| 6b | 1.3 | 50 | 6/2 | Grade 3 fatigue Grade 3 peripheral neuropathy |
| 7b | 1.3 | 60 | 8/2 | Grade 3 febrile neutropenia Grade 3 tumor lysis syndrome |
|
The protocol underwent a mandatory amendment at dose level 7 (prior to reaching the MTD of the pre-hybrid schedule) to pursue a hybrid dosing schedule (28). After determining the MTD of the hybrid-dosing schedule, accrual resumed to the pre-hybrid dosing schedule at dose level 8. Patients were enrolled through dose level 9, when DLTs required retrograde expansion of dose levels 8 through 6 in order to find the MTD of the pre-hybrid schedule. | ||||
| 8b | 1.3 | 75 | 6/2 | Grade 3 diarrhea Grade 3 esophagitis/oral mucositis |
| 9b | 1.3 | 90 | 3/2 | Grade 3 febrile neutropenia Omission of 2 scheduled treatments due to neutropeniac |
a
Maximum tolerated dose (MTD)
b
Exceeded MTD
c
Cycle 1 Day 4 treatment omitted for grade 4 ANC; Cycle 1 Day 8 treatment omitted for grade 3 ANC. Because the grade 4 ANC lasted less than 7 d, it was not by itself a DLT by the criteria in the protocol; however, it met DLT criteria by prompting 2 dose omissions in Cycle 1.