301
CPX-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia
Phase 3N = 309NCT01696084
- Population
- Adults aged 60 to 75 years with newly diagnosed high-risk or secondary AML (WHO 2008 criteria), no previous induction therapy, ECOG performance status 0 to 2.
- Design
- Open-label, multicentre, randomised (1:1) phase 3 trial at 39 academic and regional centres in the USA and Canada; stratified by age and AML subtype; up to two induction cycles then consolidation. Enrolled December 2012 to November 2014. Primary outcome overall survival in all randomised patients.
- Primary endpoint
- OS
- Arms
- CPX-351 (experimental, n = 153): CPX-351 100 units/m2 as a 90-minute infusion on days 1, 3 and 5 (days 1 and 3 for second induction); consolidation 65 units/m2 on days 1 and 3
- 7+3 (control, n = 156): Cytarabine 100 mg/m2 per day by continuous infusion for 7 days plus daunorubicin 60 mg/m2 on days 1, 2 and 3 (second induction and consolidation: cytarabine for 5 days plus daunorubicin on days 1 and 2)
- People
- Lancet JE
OSHR 0.69 (95% CI 0.52–0.90)Δ median OS+3.61 monthsΔ Overall remission rate+14.4 pointsΔ Early mortality−4.7 pointsΔ Early mortality−7.5 pointsOSHR 0.70 (95% CI 0.55–0.91)
Show the numbers
| Endpoint | Analysis | CPX-351 | 7+3 | Effect |
|---|---|---|---|---|
| OSRandomised patients (309); intention-to-treat population for efficacy per the 2018 full text and the 2021 abstract | primaryLancet 2018 | median 9.56 months | median 5.95 months | HR 0.69 (95% CI 0.52–0.90)P=.003One-sided P value, as published. |
| Overall remission rateRandomised patients (309) | primaryLancet 2018 | 47.7% | 33.3% | P=.016Two-sided P value, as published. The full text of the 2018 report defines the overall remission rate as complete remission plus complete remission with incomplete count recovery (CR+CRi); CR alone was 37.3% v 25.6% (two-sided P=.040), not recorded as a result. |
| Early mortalityRandomised patients (309) | primaryLancet 2018 | 5.9% | 10.6% | P=.149Mortality through day 30, two-sided P value as published. |
| Early mortalityRandomised patients (309) | primaryLancet 2018 | 13.7% | 21.2% | P=.097Mortality through day 60, two-sided P value as published. |
| OSRandomised patients (309) | finalLancet 2021 | median 9.33 months (6.37–11.86); 18% at 5 y (12–25%) | median 5.95 months (4.99–7.75); 8% at 5 y (4–13%) | HR 0.70 (95% CI 0.55–0.91)Prospectively planned final 5-year analysis. Median follow-up 60.91 months (IQR 60.06-62.98) in the CPX-351 group and 59.93 months (59.73-60.50) in the 7+3 group. Progressive leukaemia was the commonest cause of death in both groups; 6 of 124 deaths (CPX-351) and 7 of 140 (7+3) were considered related to study treatment. |
| Endpoint | Analysis | CPX-351 | 7+3 | Effect |
|---|---|---|---|---|
| OSRandomised patients (309); intention-to-treat population for efficacy per the 2018 full text and the 2021 abstract | primaryLancet 2018 | median 9.56 months | median 5.95 months | HR 0.69 (95% CI 0.52–0.90)P=.003One-sided P value, as published. |
| Overall remission rateRandomised patients (309) | primaryLancet 2018 | 47.7% | 33.3% | P=.016Two-sided P value, as published. The full text of the 2018 report defines the overall remission rate as complete remission plus complete remission with incomplete count recovery (CR+CRi); CR alone was 37.3% v 25.6% (two-sided P=.040), not recorded as a result. |
| Early mortalityRandomised patients (309) | primaryLancet 2018 | 5.9% | 10.6% | P=.149Mortality through day 30, two-sided P value as published. |
| Early mortalityRandomised patients (309) | primaryLancet 2018 | 13.7% | 21.2% | P=.097Mortality through day 60, two-sided P value as published. |
| OSRandomised patients (309) | finalLancet 2021 | median 9.33 months (6.37–11.86); 18% at 5 y (12–25%) | median 5.95 months (4.99–7.75); 8% at 5 y (4–13%) | HR 0.70 (95% CI 0.55–0.91)Prospectively planned final 5-year analysis. Median follow-up 60.91 months (IQR 60.06-62.98) in the CPX-351 group and 59.93 months (59.73-60.50) in the 7+3 group. Progressive leukaemia was the commonest cause of death in both groups; 6 of 124 deaths (CPX-351) and 7 of 140 (7+3) were considered related to study treatment. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| OS | 0.69 | 0.52–0.9 |
| OS | 0.7 | 0.55–0.91 |
- CPX-351 (experimental)
- 7+3 (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | CPX-351 | 7+3 |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 6 | 64.7% | 49.7% |
| 12 | 41.9% | 24.7% |
| 18 | 27.1% | 12.3% |
| 24 | 17.5% | 6.1% |
- CPX-351 (experimental)
- 7+3 (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | CPX-351 | 7+3 |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 6 | 64.0% | 49.7% |
| 12 | 41.0% | 24.7% |
| 17 | 28.3% | 13.8% |
| 23 | 18.1% | 6.9% |
Appears in
Sources
Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, et al. CPX-351 (cytarabine and daunorubicin) Liposome for Injection Versus Conventional Cytarabine Plus Daunorubicin in Older Patients With Newly Diagnosed Secondary Acute Myeloid Leukemia. J Clin Oncol. 2018;36(26):2684-2692.
Lancet JE, Uy GL, Newell LF, Lin TL, Ritchie EK, Stuart RK, et al. CPX-351 versus 7+3 cytarabine and daunorubicin chemotherapy in older adults with newly diagnosed high-risk or secondary acute myeloid leukaemia: 5-year results of a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2021;8(7):e481-e491.