Dose escalation schema, DLTs, and responses based on dose level in the CLAG-M/sorafenib phase 1 cohort (n = 46)
| Dose level . | Mitoxantrone dose (mg/m2)∗ . | Sorafenib dose (mg) . | Response . | DLT (n = 1) . |
|---|---|---|---|---|
| 1 (n = 6) | 10 | 200, daily | 3 MRD– CR 2 MRD+ CR 1 MRD– CRi | None |
| 2 (n = 6) | 12 | 200, bid | 6 MRD– CR | Intracranial hemorrhage |
| 3 (n = 11) | 15 | 200, bid | 8 MRD– CR 2 MLFS 1 resistant disease | Prolonged marrow aplasia |
| 4 (n = 8) | 18 | 200, bid | 4 MRD– CR 1 MRD– CRi 3 Resistant disease | Severe sepsis |
| 5 (n = 9) | 18 | 400, qAM, 200, qPM | 9 MRD– CR | None |
| 6 (n = 6) | 18 | 400 mg bid | 6 MRD– CR | Cardiomyopathy |
| Dose level . | Mitoxantrone dose (mg/m2)∗ . | Sorafenib dose (mg) . | Response . | DLT (n = 1) . |
|---|---|---|---|---|
| 1 (n = 6) | 10 | 200, daily | 3 MRD– CR 2 MRD+ CR 1 MRD– CRi | None |
| 2 (n = 6) | 12 | 200, bid | 6 MRD– CR | Intracranial hemorrhage |
| 3 (n = 11) | 15 | 200, bid | 8 MRD– CR 2 MLFS 1 resistant disease | Prolonged marrow aplasia |
| 4 (n = 8) | 18 | 200, bid | 4 MRD– CR 1 MRD– CRi 3 Resistant disease | Severe sepsis |
| 5 (n = 9) | 18 | 400, qAM, 200, qPM | 9 MRD– CR | None |
| 6 (n = 6) | 18 | 400 mg bid | 6 MRD– CR | Cardiomyopathy |
bid, twice daily; MLFS, morphologic leukemia–free state; qAM, every morning; qPM, every evening.
Dosing based on body surface area, using actual patient weight.