Dasatinib versus imatinib with intensive chemotherapy without prophylactic cranial irradiation in children with Philadelphia chromosome-positive acute lymphoblastic leukemia: a randomized clinical trial (China)
Phase 3N = 189
- Population
- Patients aged 0 to 18 years with Ph+ ALL: 189 available for analysis (225 with the diagnosis; 35 declined participation and 1 died before treatment).
- Design
- Open-label phase 3 randomised clinical trial at 20 hospitals in China (enrolment January 2015 to September 2018; randomisation stopped in October 2018 when the early stopping criterion was met). Daily dasatinib 80 mg/m2 or imatinib 300 mg/m2, given continuously from diagnosis through continuation therapy, within intensive chemotherapy without prophylactic cranial irradiation. Primary outcome EFS by intention to treat. Registered with the Chinese Clinical Trial Registry (ChiCTR-IPR-14005706); no ClinicalTrials.gov record cited. The primary analysis followed a planned interim analysis at 3.5 years (3-year EFS significantly better with dasatinib), after which the data and safety monitoring committee recommended stopping randomisation; outcome data were updated on 31 May 2019.
- Primary endpoint
- EFS
- Arms
- Dasatinib (experimental, n = 92): Dasatinib 80 mg/m2 daily with intensive chemotherapy
- Imatinib (control, n = 97): Imatinib mesylate 300 mg/m2 daily with intensive chemotherapy
- People
- Shen S, senior author Pui CH
Δ 48-month EFS+22.1 pointsΔ 48-month OS+19.2 pointsΔ 48-month CIR−14.6 pointsΔ 48-month CNS relapse−5.7 points
Show the numbers
| Endpoint | Analysis | Dasatinib | Imatinib | Effect |
|---|---|---|---|---|
| EFSRandomised patients available for analysis (189); intention to treat as stated in the abstractEvent-free survival at 4 years (primary outcome) | primarymedian follow-up 26.4 monthsShen 2020 | 71% at 4 y (56.2–89.6%) | 48.9% at 4 y (32.0–74.5%) | P=0.005Log-rank test. Median follow-up 26.4 months (IQR 16.3-34.1). Randomisation stopped after a planned interim analysis; seven patients who left protocol treatment on physician decision were counted as failures, and 18 who abandoned or withdrew were censored in the intention-to-treat analysis (full text). |
| OSRandomised patients available for analysis (189)Overall survival at 4 years (secondary outcome) | primarymedian follow-up 26.4 monthsShen 2020 | 88.4% at 4 y (81.3–96.1%) | 69.2% at 4 y (55.6–86.2%) | P=0.04Log-rank test. |
| CIRRandomised patients available for analysis (189)Four-year cumulative risk of any relapse (secondary outcome) | primaryShen 2020 | 19.8% at 4 y (4.2–35.4%) | 34.4% at 4 y (15.6–53.2%) | P=0.01Gray test. |
| CNS relapseRandomised patients available for analysis (189)Four-year cumulative risk of isolated CNS relapse | primaryShen 2020 | 2.7% at 4 y (0.0–8.1%) | 8.4% at 4 y (1.2–15.6%) | P=0.06Gray test. |
| Endpoint | Analysis | Dasatinib | Imatinib | Effect |
|---|---|---|---|---|
| EFSRandomised patients available for analysis (189); intention to treat as stated in the abstractEvent-free survival at 4 years (primary outcome) | primarymedian follow-up 26.4 monthsShen 2020 | 71% at 4 y (56.2–89.6%) | 48.9% at 4 y (32.0–74.5%) | P=0.005Log-rank test. Median follow-up 26.4 months (IQR 16.3-34.1). Randomisation stopped after a planned interim analysis; seven patients who left protocol treatment on physician decision were counted as failures, and 18 who abandoned or withdrew were censored in the intention-to-treat analysis (full text). |
| OSRandomised patients available for analysis (189)Overall survival at 4 years (secondary outcome) | primarymedian follow-up 26.4 monthsShen 2020 | 88.4% at 4 y (81.3–96.1%) | 69.2% at 4 y (55.6–86.2%) | P=0.04Log-rank test. |
| CIRRandomised patients available for analysis (189)Four-year cumulative risk of any relapse (secondary outcome) | primaryShen 2020 | 19.8% at 4 y (4.2–35.4%) | 34.4% at 4 y (15.6–53.2%) | P=0.01Gray test. |
| CNS relapseRandomised patients available for analysis (189)Four-year cumulative risk of isolated CNS relapse | primaryShen 2020 | 2.7% at 4 y (0.0–8.1%) | 8.4% at 4 y (1.2–15.6%) | P=0.06Gray test. |