Table 1.
Overview of clinical safety for CPX-351 in AML
| Study | Phase (N) | Patient population | Common adverse events | Early mortality | Median time to neutrophil recovery |
|---|---|---|---|---|---|
| Study 101 NCT0038942822 |
I (48) |
Relapsed/refractory AML or ALL or high-risk MDS | DLTs: congestive heart failure, hypertensive crisis, persistent cytopenias beyond 56 days (in 1 patient each) | ||
| Study 204 NCT0078889224 |
II (126) |
Newly diagnosed AML in patients aged ≥60 and ≤75 years |
CPX-351 vs 7+3, respectively: Common (>15%) grade ≥3 adverse events: febrile neutropenia, 63.5% vs 51.2%; bacteremia, 35.3% vs 19.5%; pneumonia, 15.3% vs 19.5%; hypokalemia, 15.3% vs 12.2% |
CPX-351 vs 7+3, respectively: 30-day: all patients, 3.5% vs 7.3% (P=0.053); high-risk, 5.8% vs 12.0%; sAML, 3.0% vs 15.8% 60-day: all patients, 4.7% vs 14.6%; high-risk; 7.7% vs 24.0%; sAML, 6.1% vs 31.6% |
CPX-351 vs 7+3, respectively: To neutrophil recovery to ≥1000/µL: 36 vs 32 days; to platelet recovery to ≥100,000/µL: 37 vs 28 days; infection-related deaths: 3.5% vs 7.3% |
| Study 205 NCT0082209426 |
II (125) |
First relapse AML in patients aged ≥18 and ≤65 years |
CPX-351 vs 7+3, respectively: Common (>15%) grade ≥3 adverse events: febrile neutropenia, 54% vs 34%; bacteremia, 30% vs 43%; pneumonia, 22% vs 9% |
CPX-351 vs 7+3, respectively: 30-day: all patients, 7.4% vs 4.5%; poor-risk, 8.9% vs 6.9% 60-day: all patients, 14.8% vs 15.9%; poor-risk, 16.1% vs 24.1% 90-day: all patients, 18.5% vs 29.5%; poor-risk, 21.4% vs 37.9% |
CPX-351 vs 7+3, respectively: To neutrophil recovery to >1000/µL, 42 vs 34 days; to platelet recovery to >100,000/µL, 45 vs 35 days; infection-related deaths: 9.9% vs 9.1% |
| Study 301 NCT0169608423 |
III (309) |
Newly diagnosed, high-risk/sAML in patients aged 60–75 years |
CPX-351 vs 7+3, respectively: Common (>15%) grade ≥3 adverse events: febrile neutropenia, 68% vs 71%; pneumonia, 20% vs 15%; and hypoxia, 13% vs 15% |
CPX-351 vs 7+3, respectively: 30-day: all patients, 5.9% vs 10.6% 60-day: all patients, 13.7% vs 21.2% |
CPX-351 vs 7+3, respectively: Patients with CR + CRi, to neutrophil recovery to >500/µL, 35 vs 29 days (first induction), 35 vs 28 days (second induction); to platelet recovery to >50,000/µL, 36.5 vs 29 days (first induction), 35 vs 24 days (second induction) |
Abbreviations: AML, acute myeloid leukemia; ALL, acute lymphoblastic leukemia; MDS, myelodysplastic syndrome; DLT, dose-limiting toxicity; sAML, secondary AML; CR, complete remission; CRi, CR with incomplete platelet or neutrophil recovery.