AALL0622
Dasatinib plus intensive chemotherapy in children, adolescents and young adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Children's Oncology Group AALL0622; Bristol Myers Squibb CA180-204)
Phase 2/3N = 60NCT00720109
- Population
- Eligible patients aged 1 to 30 years with newly diagnosed Ph+ ALL (60 enrolled)
- Design
- Single-arm Children's Oncology Group study of the safety and feasibility of adding dasatinib to intensive chemotherapy from induction day 15. Transplant was recommended for high-risk (slow-response) patients and for those with a matched family donor after at least 11 weeks of therapy; standard-risk (rapid-response) patients received chemotherapy plus dasatinib for a further 120 weeks; overt CNS leukemia received cranial irradiation. Registry lists phase 2/3. Outcomes were compared by the authors with COG AALL0031.
- Primary endpoint
- EFS
- Arms
- Dasatinib plus chemotherapy (experimental, n = 60): Dasatinib 60 mg/m2 once daily from induction day 15 with intensive chemotherapy (cohort 1 discontinuous, 2 weeks of each block; cohort 2 continuous)
- AALL0031 cohorts 4 and 5 (imatinib) (control, n = 54): Same chemotherapy with continuous imatinib, COG AALL0031 cohorts 4 and 5 including patients who had transplant (separate earlier trial, used by the authors for comparison)
- People
- Slayton WB, senior author Hunger SP, Children's Oncology Group
Δ 60-month OS+5 pointsΔ 60-month DFS−8 pointsΔ 60-month CNS relapse+8.8 points
Show the numbers
| Endpoint | Analysis | Dasatinib plus chemotherapy | AALL0031 cohorts 4 and 5 (imatinib) | Effect |
|---|---|---|---|---|
| OSEligible enrolled patients in AALL0622 (n=60) compared with AALL0031 cohorts 4 and 5 (n=54), both including patients who had transplant (cross-trial comparison reported by the authors)Overall survival at 5 years | exploratorySlayton 2018 | 86% at 5 y | 81% at 5 y | P=0.63Reported as 86% ± 5% (AALL0622) and 81% ± 6% (AALL0031). The abstract labels the ± values as standard deviations; Methods state standard errors by Peto and Peto. Cross-trial comparison, not randomised. |
| DFSEligible enrolled patients in AALL0622 (n=60) compared with AALL0031 cohorts 4 and 5 (n=54), both including patients who had transplant (cross-trial comparison reported by the authors)Disease-free survival at 5 years | exploratorySlayton 2018 | 60% at 5 y | 68% at 5 y | P=0.31Reported as 60% ± 7% (AALL0622) and 68% ± 7% (AALL0031). The abstract labels the ± values as standard deviations; Methods state standard errors by Peto and Peto. Cross-trial comparison, not randomised. |
| EFSStandard-risk patients (n=48 in the 5-year analysis)Event-free survival at 3 years in standard-risk (rapid-response) patients (primary outcome: achievement of 3-year EFS of at least 60%) | primarySlayton 2018 | 84.6% at 3 y | — | Reported as 84.6% ± 5.7% (± labelled standard deviation in the full text). Not stated in the abstract. |
| EFSEligible enrolled patients (60)Event-free survival at 5 years | long term-updateSlayton 2018 | 60% at 5 y | — | Reported as 60% ± 7% overall; 61% ± 7% in standard-risk patients (n=48, 19% underwent transplant) and 67% ± 19% in high-risk patients (n=9, 89% underwent transplant). The ± values are labelled standard deviations in the abstract. The trial's primary outcome was 3-year EFS in standard-risk patients (see efs-3y-standard-risk); the 5-year figures are a longer-follow-up report (data current as of December 2016). |
| CNS relapseNon-transplanted, non-CNS3 patients in AALL0622 (n=40; 6 CNS relapses) compared with the corresponding AALL0031 patients given continuous imatinib and cranial irradiation (n=31; 2 CNS relapses)Five-year cumulative incidence of isolated or combined CNS relapse | long term-updateSlayton 2018 | 15.4% at 5 y | 6.6% at 5 y | P=0.30Reported as 15.4% ± 5.9% (abstract: 15% ± 6%, not restating the subset) versus 6.6% ± 4.6% in AALL0031 (P=0.30, not significant). The abstract does not say that the 15% applies to the 40 non-transplanted, non-CNS3 patients rather than all 60. In AALL0031 all patients received cranial irradiation; the AALL0622 authors described the CNS relapse rate as surprisingly high and as contributing in part to EFS not improving. |
| Endpoint | Analysis | Dasatinib plus chemotherapy | AALL0031 cohorts 4 and 5 (imatinib) | Effect |
|---|---|---|---|---|
| OSEligible enrolled patients in AALL0622 (n=60) compared with AALL0031 cohorts 4 and 5 (n=54), both including patients who had transplant (cross-trial comparison reported by the authors)Overall survival at 5 years | exploratorySlayton 2018 | 86% at 5 y | 81% at 5 y | P=0.63Reported as 86% ± 5% (AALL0622) and 81% ± 6% (AALL0031). The abstract labels the ± values as standard deviations; Methods state standard errors by Peto and Peto. Cross-trial comparison, not randomised. |
| DFSEligible enrolled patients in AALL0622 (n=60) compared with AALL0031 cohorts 4 and 5 (n=54), both including patients who had transplant (cross-trial comparison reported by the authors)Disease-free survival at 5 years | exploratorySlayton 2018 | 60% at 5 y | 68% at 5 y | P=0.31Reported as 60% ± 7% (AALL0622) and 68% ± 7% (AALL0031). The abstract labels the ± values as standard deviations; Methods state standard errors by Peto and Peto. Cross-trial comparison, not randomised. |
| EFSStandard-risk patients (n=48 in the 5-year analysis)Event-free survival at 3 years in standard-risk (rapid-response) patients (primary outcome: achievement of 3-year EFS of at least 60%) | primarySlayton 2018 | 84.6% at 3 y | — | Reported as 84.6% ± 5.7% (± labelled standard deviation in the full text). Not stated in the abstract. |
| EFSEligible enrolled patients (60)Event-free survival at 5 years | long term-updateSlayton 2018 | 60% at 5 y | — | Reported as 60% ± 7% overall; 61% ± 7% in standard-risk patients (n=48, 19% underwent transplant) and 67% ± 19% in high-risk patients (n=9, 89% underwent transplant). The ± values are labelled standard deviations in the abstract. The trial's primary outcome was 3-year EFS in standard-risk patients (see efs-3y-standard-risk); the 5-year figures are a longer-follow-up report (data current as of December 2016). |
| CNS relapseNon-transplanted, non-CNS3 patients in AALL0622 (n=40; 6 CNS relapses) compared with the corresponding AALL0031 patients given continuous imatinib and cranial irradiation (n=31; 2 CNS relapses)Five-year cumulative incidence of isolated or combined CNS relapse | long term-updateSlayton 2018 | 15.4% at 5 y | 6.6% at 5 y | P=0.30Reported as 15.4% ± 5.9% (abstract: 15% ± 6%, not restating the subset) versus 6.6% ± 4.6% in AALL0031 (P=0.30, not significant). The abstract does not say that the 15% applies to the 40 non-transplanted, non-CNS3 patients rather than all 60. In AALL0031 all patients received cranial irradiation; the AALL0622 authors described the CNS relapse rate as surprisingly high and as contributing in part to EFS not improving. |
Appears in
Sources
Slayton WB, Schultz KR, Kairalla JA, Devidas M, Mi X, Pulsipher MA, et al. Dasatinib Plus Intensive Chemotherapy in Children, Adolescents, and Young Adults With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: Results of Children's Oncology Group Trial AALL0622. J Clin Oncol. 2018;36(22):2306-2314.