Table 3.
Dose-limiting toxic effects observed at each dose level (mg/m2 per dose twice daily) by cohort
| Number of patients entered | Number of patients evaluable | Number of patients with cycle 1 DLT | Cycle 1 DLT type (number) | Subsequent cycle DLT type (number) | |
|---|---|---|---|---|---|
|
Part A1 relapsed or refractory solid tumours, including CNS tumours or ALCL
| |||||
| 100 | 4 | 3 | 0 | None | None |
| 130 | 6 | 4 | 0 | None | Neutrophil count decreased (1) |
| 165 | 8 | 6 | 0 | None | Diarrhoea (1) |
|
| |||||
|
Part A1*
| |||||
| 215 | 8 | 7 | 2 | Dizziness (1); intracranial haemorrhage (1) | None |
|
| |||||
|
Part A1 relapsed or refractory solid tumours, including ALCL; CNS tumours excluded
| |||||
| 280 | 6 | 5 | 0 | None | Diarrhoea (1); skin infection (1) |
| 365 | 11 | 6 | 2 | Increased alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, and GGT (1); neutrophil count decreased (1) | Alkaline phosphatase increased (1); neutrophil count decreased (1) |
|
| |||||
|
Part A2 recurrent or refractory malignancies with confirmed ALK fusion proteins or ALK mutations
| |||||
| 100 | 2 | 2 | 0 | None | Increased alanine aminotransferase and aspartate aminotransferase (1) |
| 165 | 12 | 12 | 1 | Neutrophil count decrease (1) | Eye disorders—blue discoloration to vision (1) |
| 215 | 1 | 1 | 0 | None | None |
| 280 | 10 | 9 | 0 | None | Oedema limbs (1), neutrophil count decreased (1) |
|
| |||||
|
A3 relapsed or refractory neuroblastoma, with or without bone marrow involvement
| |||||
| 130 | 2 | 1 | 0 | None | None |
| 165 | 3 | 3 | 0 | None | None |
| 215 | 3 | 3 | 0 | None | None |
| 280 | 3 | 3 | 0 | None | None |
DLT=dose-limiting toxicity. ALCL=anaplastic large-cell lymphoma. GGT=gamma-glutamyl transpeptidase.
*
A1: 215 mg/m2 per dose level initially included patients with CNS tumours but was subsequently amended to exclude patients with known primary or metastatic CNS disease.