AALL0031
Imatinib with intensive chemotherapy for children and adolescents with Philadelphia chromosome-positive acute lymphoblastic leukemia (Children's Oncology Group AALL0031)
N = 92NCT00022737
- Population
- Children and adolescents aged 1 to 21 years with Ph+ ALL (N=92); 65 Ph-negative patients given the same chemotherapy served as the toxicity comparison.
- Design
- Non-randomised Children's Oncology Group study in five sequential cohorts with progressively longer imatinib exposure (42 to 280 continuous days before maintenance), compared with historical controls for event-free survival and with Ph-negative patients given the same chemotherapy without imatinib for toxicity. Patients with HLA-identical sibling donors underwent transplant, with imatinib for 6 months afterwards.
- Primary endpoint
- EFS
- Arms
- Historical controls (POG) (control, n = 120): Chemotherapy without imatinib: patients on earlier Pediatric Oncology Group protocols ALinC 14, 15 and 16 (1986-1999), induction failures excluded (N=120)
- Cohort 5 (experimental, n = 50): Imatinib 340 mg/m2/day for 280 continuous days before maintenance, with intensive chemotherapy
- Cohort 5, chemotherapy plus imatinib (experimental): Intensive chemotherapy plus imatinib 340 mg/m2/day, without transplant (non-randomised subgroup of cohort 5: n=25 in the 2009 report, n=28 in the 5-year follow-up)
- Sibling-donor transplant (control): Transplant from an HLA-identical sibling donor, with imatinib for 6 months afterwards (non-randomised; patients from all cohorts, 21 in total, 13 of them in cohort 5)
- Unrelated-donor transplant (control): Transplant from an unrelated or other alternative donor, off protocol (non-randomised; patients from all cohorts; n=11 in the 2009 report, n=13 in the 5-year follow-up)
- People
- Schultz KR, senior author Camitta B, Children's Oncology Group
Δ 36-month EFS+45 pointsΔ 36-month EFS+31 pointsΔ 60-month DFS+5 points
Show the numbers
| Endpoint | Analysis | Cohort 5 / Cohort 5, chemotherapy plus imatinib | Historical controls (POG) / Sibling-donor transplant / Unrelated-donor transplant | Effect |
|---|---|---|---|---|
| EFSCohort 5 patients given continuous imatinib (n=44 in the comparison, including those assigned to sibling-donor transplant) versus historical POG controls (N=120, induction failures excluded); non-randomisedEvent-free survival at 3 years | primarySchultz 2009 | 80% at 3 y (64–90%) | 35% at 3 y | P<0.0001The abstract reports 80% ± 11% for cohort 5 and 35% ± 4% for historical controls; the full text gives 80.5% ± 11.2% (95% CI 64.5-89.8) and 35.0% ± 4.4%. The ± values are standard errors (Peto and Peto method, stated in Methods). Historical controls are patients on earlier POG protocols ALinC 14, 15 and 16 (1986-1999), with induction failures excluded. |
| EFSCohort 5 patients treated with chemotherapy plus imatinib (n=25) versus patients of all cohorts who had a matched-sibling transplant (n=21, of whom 13 were in cohort 5); non-randomisedEvent-free survival at 3 years | exploratorySchultz 2009 | 88% at 3 y (66–96%) | 57% at 3 y (30.4–76.1%) | Described in the abstract as similar; the abstract gives no P value and reports 88% ± 11% and 57% ± 22%. Full text: 87.7% ± 10.9% (95% CI 66.4-95.8) versus 56.6% ± 21.5% (30.4-76.1); the three-group comparison, which also includes alternative-donor transplant (n=11; 71.6% ± 19.0%) gave P=0.14 and is not shown here. The ± values are standard errors. |
| DFSCohort 5 patients given chemotherapy plus imatinib (n=28) versus sibling-donor (n=21) and unrelated-donor (n=13) transplant patients from all cohorts; non-randomisedDisease-free survival at 5 years | long term-updateSchultz 2014 | 70% at 5 y | 65% at 5 y | P=0.60Group sizes in the 5-year analysis: n=28, 21 and 13. The abstract reports 70% ± 12%, 65% ± 11% and 59% ± 15%; the ± values are standard errors (Peto and Peto). The single P value is the log-rank comparison across the three groups (full text Results, Fig 1a); the transplant groups are drawn from all cohorts, not only cohort 5. |
| Endpoint | Analysis | Cohort 5 / Cohort 5, chemotherapy plus imatinib | Historical controls (POG) / Sibling-donor transplant / Unrelated-donor transplant | Effect |
|---|---|---|---|---|
| EFSCohort 5 patients given continuous imatinib (n=44 in the comparison, including those assigned to sibling-donor transplant) versus historical POG controls (N=120, induction failures excluded); non-randomisedEvent-free survival at 3 years | primarySchultz 2009 | 80% at 3 y (64–90%) | 35% at 3 y | P<0.0001The abstract reports 80% ± 11% for cohort 5 and 35% ± 4% for historical controls; the full text gives 80.5% ± 11.2% (95% CI 64.5-89.8) and 35.0% ± 4.4%. The ± values are standard errors (Peto and Peto method, stated in Methods). Historical controls are patients on earlier POG protocols ALinC 14, 15 and 16 (1986-1999), with induction failures excluded. |
| EFSCohort 5 patients treated with chemotherapy plus imatinib (n=25) versus patients of all cohorts who had a matched-sibling transplant (n=21, of whom 13 were in cohort 5); non-randomisedEvent-free survival at 3 years | exploratorySchultz 2009 | 88% at 3 y (66–96%) | 57% at 3 y (30.4–76.1%) | Described in the abstract as similar; the abstract gives no P value and reports 88% ± 11% and 57% ± 22%. Full text: 87.7% ± 10.9% (95% CI 66.4-95.8) versus 56.6% ± 21.5% (30.4-76.1); the three-group comparison, which also includes alternative-donor transplant (n=11; 71.6% ± 19.0%) gave P=0.14 and is not shown here. The ± values are standard errors. |
| DFSCohort 5 patients given chemotherapy plus imatinib (n=28) versus sibling-donor (n=21) and unrelated-donor (n=13) transplant patients from all cohorts; non-randomisedDisease-free survival at 5 years | long term-updateSchultz 2014 | 70% at 5 y | 65% at 5 y | P=0.60Group sizes in the 5-year analysis: n=28, 21 and 13. The abstract reports 70% ± 12%, 65% ± 11% and 59% ± 15%; the ± values are standard errors (Peto and Peto). The single P value is the log-rank comparison across the three groups (full text Results, Fig 1a); the transplant groups are drawn from all cohorts, not only cohort 5. |
Appears in
Sources
Schultz KR, Bowman WP, Aledo A, Slayton WB, Sather H, Devidas M, et al. Improved early event-free survival with imatinib in Philadelphia chromosome-positive acute lymphoblastic leukemia: a children's oncology group study. J Clin Oncol. 2009;27(31):5175-81.
Schultz KR, Carroll A, Heerema NA, Bowman WP, Aledo A, Slayton WB, et al. Long-term follow-up of imatinib in pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia: Children's Oncology Group study AALL0031. Leukemia. 2014;28(7):1467-71.