EsPhALL2004
Imatinib after induction for children and adolescents with Philadelphia-chromosome-positive acute lymphoblastic leukaemia (EsPhALL): a randomised, open-label, intergroup study
N = 178NCT00287105
- Population
- Patients aged 1-18 years with t(9;22)(q34;q11) recruited to national front-line ALL trials: 108 good risk and 70 poor risk.
- Design
- Intergroup open-label study enrolled by ten study groups (2004 to 2009). Good-risk patients (by early response) were randomly assigned 1:1 to post-induction imatinib with chemotherapy or chemotherapy only; all poor-risk patients received post-induction imatinib with chemotherapy. Berlin-Frankfurt-Munster high-risk chemotherapy backbone, then eligibility for stem-cell transplantation after four post-induction blocks. Registered at ClinicalTrials.gov as phase 2 (registry enrolment 49; the paper reports 178).
- Primary endpoint
- DFS, EFS
- Arms
- Good risk, imatinib (experimental, n = 46): Post-induction imatinib with chemotherapy (good-risk patients randomised)
- Good risk, no imatinib (control, n = 44): Post-induction chemotherapy only (good-risk patients randomised)
- Poor risk, imatinib (experimental, n = 70): Post-induction imatinib with chemotherapy (all poor-risk patients; not randomised)
- People
- Biondi A, senior author Valsecchi MG
DFSHR 0.63 (95% CI 0.28–1.41)Δ 48-month DFS+11.2 pointsΔ 48-month DFS+19.3 points
Show the numbers
| Endpoint | Analysis | Good risk, imatinib / Poor risk, imatinib | Good risk, no imatinib | Effect |
|---|---|---|---|---|
| DFSGood-risk randomised patients; intention-to-treat analysis as stated for the primary endpoints in the abstractDisease-free survival at 4 years in the good-risk group (primary endpoint) | primarymedian follow-up 3.1 yearsBiondi 2012 | 72.9% at 4 y (56.1–84.1%) | 61.7% at 4 y (45.0–74.7%) | HR 0.63 (95% CI 0.28–1.41)P=0.24The hazard ratio is for any event, adjusted for post-induction minimal residual disease (HR 0.63, 95% CI 0.28-1.41, p=0.26 Wald); the unadjusted HR in the full text is 0.71 (95% CI 0.33-1.54, p=0.38). The p=0.24 is the log-rank comparison of DFS. MRD was unexpectedly imbalanced between the randomised groups, favouring the no-imatinib group. Median follow-up 3.1 years (IQR 2.0-4.6). |
| DFSGood-risk patients grouped by imatinib actually received (as-treated secondary analysis)Disease-free survival at 4 years in the good-risk group, as-treated analysis | exploratoryBiondi 2012 | 75.2% at 4 y (61.0–84.9%) | 55.9% at 4 y (36.1–71.7%) | P=0.06Secondary as-treated analysis reported in addition to the intention-to-treat primary analysis. |
| EFSPoor-risk patients, all treated with imatinib (single group)Event-free survival at 4 years in the poor-risk group (primary endpoint) | primaryBiondi 2012 | 53.5% at 4 y (40.4–65.0%) | — | — |
| Endpoint | Analysis | Good risk, imatinib / Poor risk, imatinib | Good risk, no imatinib | Effect |
|---|---|---|---|---|
| DFSGood-risk randomised patients; intention-to-treat analysis as stated for the primary endpoints in the abstractDisease-free survival at 4 years in the good-risk group (primary endpoint) | primarymedian follow-up 3.1 yearsBiondi 2012 | 72.9% at 4 y (56.1–84.1%) | 61.7% at 4 y (45.0–74.7%) | HR 0.63 (95% CI 0.28–1.41)P=0.24The hazard ratio is for any event, adjusted for post-induction minimal residual disease (HR 0.63, 95% CI 0.28-1.41, p=0.26 Wald); the unadjusted HR in the full text is 0.71 (95% CI 0.33-1.54, p=0.38). The p=0.24 is the log-rank comparison of DFS. MRD was unexpectedly imbalanced between the randomised groups, favouring the no-imatinib group. Median follow-up 3.1 years (IQR 2.0-4.6). |
| DFSGood-risk patients grouped by imatinib actually received (as-treated secondary analysis)Disease-free survival at 4 years in the good-risk group, as-treated analysis | exploratoryBiondi 2012 | 75.2% at 4 y (61.0–84.9%) | 55.9% at 4 y (36.1–71.7%) | P=0.06Secondary as-treated analysis reported in addition to the intention-to-treat primary analysis. |
| EFSPoor-risk patients, all treated with imatinib (single group)Event-free survival at 4 years in the poor-risk group (primary endpoint) | primaryBiondi 2012 | 53.5% at 4 y (40.4–65.0%) | — | — |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| DFS | 0.63 | 0.28–1.41 |
Appears in
Sources
Biondi A, Schrappe M, De Lorenzo P, Castor A, Lucchini G, Gandemer V, et al. Imatinib after induction for treatment of children and adolescents with Philadelphia-chromosome-positive acute lymphoblastic leukaemia (EsPhALL): a randomised, open-label, intergroup study. Lancet Oncol. 2012;13(9):936-45.