CA180-372/AALL1122
Dasatinib with intensive chemotherapy in de novo paediatric Philadelphia chromosome-positive acute lymphoblastic leukaemia (CA180-372/COG AALL1122): a single-arm, multicentre, phase 2 trial
Phase 2N = 106NCT01460160
- Population
- Patients aged over 1 year and under 18 years with newly diagnosed Ph+ ALL and performance status of at least 60% (106 treated; 109 enrolled).
- Design
- Joint Children's Oncology Group and European (EsPhALL) open-label single-arm phase 2 study: EsPhALL chemotherapy plus dasatinib 60 mg/m2 orally once daily from induction day 15. Primary endpoint was 3-year EFS compared with external historical controls (the AIEOP-BFM 2000 high-risk group, and the EsPhALL 2010 imatinib cohort). Patients with MRD of at least 0.05% after induction 1B, or MRD-positive after three consolidation blocks, were classed high risk and allocated to transplant in first remission; others received chemotherapy plus dasatinib for 2 years.
- Primary endpoint
- EFS
- Arms
- Dasatinib plus EsPhALL chemotherapy (experimental, n = 106): Dasatinib 60 mg/m2 orally once daily from induction day 15 with EsPhALL chemotherapy
- Chemotherapy alone (historical) (control): Chemotherapy alone, AIEOP-BFM 2000 high-risk group (external historical control)
- Imatinib plus chemotherapy (historical) (control): Imatinib plus chemotherapy, EsPhALL 2010 cohort (external historical control)
- People
- Hunger SP, senior author Biondi A, Children's Oncology Group; EsPhALL European intergroup
Δ 36-month EFS+16.3 pointsΔ 36-month EFS+6.4 points
Show the numbers
| Endpoint | Analysis | Dasatinib plus EsPhALL chemotherapy | Chemotherapy alone (historical) / Imatinib plus chemotherapy (historical) | Effect |
|---|---|---|---|---|
| EFSAll treated patients who received at least one dasatinib dose (106), compared with external historical controlsEvent-free survival at 3 years (primary endpoint) | primaryHunger 2023 | 65.5% at 3 y | 49.2% at 3 y | P=0.032Intervals in the abstract are 90% Clopper-Pearson CIs: 57.7 to 73.7 for dasatinib plus chemotherapy and 38.0 to 60.4 for chemotherapy alone. Comparison with an external historical control group, not randomised. |
| EFSAll treated patients who received at least one dasatinib dose (106), compared with the EsPhALL 2010 historical cohortEvent-free survival at 3 years (primary endpoint) | primaryHunger 2023 | 65.5% at 3 y | 59.1% at 3 y | P=0.27The p value is for superiority over imatinib plus chemotherapy. The abstract states non-inferiority (margin -5%): 90% CI of the treatment difference -3.3 to 17.2. The abstract gives 51.8 to 66.2 for the imatinib plus chemotherapy cohort without restating the interval level. |
| Endpoint | Analysis | Dasatinib plus EsPhALL chemotherapy | Chemotherapy alone (historical) / Imatinib plus chemotherapy (historical) | Effect |
|---|---|---|---|---|
| EFSAll treated patients who received at least one dasatinib dose (106), compared with external historical controlsEvent-free survival at 3 years (primary endpoint) | primaryHunger 2023 | 65.5% at 3 y | 49.2% at 3 y | P=0.032Intervals in the abstract are 90% Clopper-Pearson CIs: 57.7 to 73.7 for dasatinib plus chemotherapy and 38.0 to 60.4 for chemotherapy alone. Comparison with an external historical control group, not randomised. |
| EFSAll treated patients who received at least one dasatinib dose (106), compared with the EsPhALL 2010 historical cohortEvent-free survival at 3 years (primary endpoint) | primaryHunger 2023 | 65.5% at 3 y | 59.1% at 3 y | P=0.27The p value is for superiority over imatinib plus chemotherapy. The abstract states non-inferiority (margin -5%): 90% CI of the treatment difference -3.3 to 17.2. The abstract gives 51.8 to 66.2 for the imatinib plus chemotherapy cohort without restating the interval level. |
Appears in
Sources
Hunger SP, Tran TH, Saha V, Devidas M, Valsecchi MG, Gastier-Foster JM, et al. Dasatinib with intensive chemotherapy in de novo paediatric Philadelphia chromosome-positive acute lymphoblastic leukaemia (CA180-372/COG AALL1122): a single-arm, multicentre, phase 2 trial. Lancet Haematol. 2023;10(7):e510-e520.