AAML1031
AAML1031 was the children's leukaemia trial that found adding bortezomib to standard chemotherapy did not help and caused more nerve damage, while a separate part of the trial suggested that adding the FLT3 blocker sorafenib does improve outcomes for children whose leukaemia carries a high load of the FLT3-ITD mutation.
Overview
AAML1031 was the Children's Oncology Group phase 3 trial for de novo acute myeloid leukaemia in patients under 30. Patients without a high allelic ratio FLT3-ITD mutation were randomised to standard chemotherapy (four courses, or three followed by allogeneic transplant for high-risk disease) with or without bortezomib on days 1, 4 and 8 of each course. Patients with high allelic ratio FLT3-ITD received sorafenib in three sequential cohorts that defined the dose and then added it to induction and as single-agent maintenance.
Bortezomib did not improve remission, event-free or overall survival and increased peripheral neuropathy and intensive care admissions. In the FLT3-ITD cohorts, patients given sorafenib had better event-free survival than a comparator group of high allelic ratio patients treated with identical chemotherapy without sorafenib, and multivariable analysis accounting for transplant and co-occurring favourable mutations confirmed the benefit. The trial is why the standard-of-care text for childhood acute myeloid leukaemia adds sorafenib to chemotherapy for high allelic ratio FLT3-ITD disease.
- 44.8 vs 47 out of 100 free of a major event at 3 years with Chemotherapy + bortezomib compared with Chemotherapy alone; 2.2 fewer per 100.
- On this measure the first group did worse, not better.
- The p-value (0.236) means the difference could plausibly be due to chance.
- This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
- 63.6 vs 67.2 out of 100 alive at 3 years with Chemotherapy + bortezomib compared with Chemotherapy alone; 3.6 fewer per 100.
- On this measure the first group did worse, not better.
- The p-value (0.356) means the difference could plausibly be due to chance.
- Overall survival counts deaths from any cause, so it is the most direct measure of whether a treatment helps people live longer.
- 89 vs 91 out of 100 had no sign of cancer on scans or tests with Chemotherapy + bortezomib compared with Chemotherapy alone; 2 fewer per 100.
- On this measure the first group did worse, not better.
- The p-value (0.531) means the difference could plausibly be due to chance.
- This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
- The treated group had about 137 percent higher chance of the event at any given time (hazard ratio 2.37).
- The absolute difference, how many more people out of 100 were helped, is not reported here.
- This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
- The treated group had about 203 percent higher chance of the event at any given time (hazard ratio 3.03).
- The absolute difference, how many more people out of 100 were helped, is not reported here.
- This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
- These results apply to the people the trial enrolled: Newly diagnosed acute myeloid leukaemia in patients under 30: standard chemotherapy with or without bortezomib (randomised), and for high allelic ratio FLT3-ITD disease the addition of sorafenib to chemotherapy and as maintenance (non-randomised cohorts). People in a different situation may not see the same effect.
- The trial selected people by a biomarker (FLT3); the result should not be assumed for people whose cancer does not have it.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
1,645 enrolled.
Numbers not yet public.
SourceNumbers not yet public.
Source| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Event-free survival at 3 years, bortezomib randomisationprimary | Chemotherapy + bortezomib | 555 | 44.8% | - | 0.236 | link |
| Chemotherapy alone | 542 | 47% | ||||
| Overall survival at 3 years, bortezomib randomisation | Chemotherapy + bortezomib | 555 | 63.6% | - | 0.356 | link |
| Chemotherapy alone | 542 | 67.2% | ||||
| Complete remission after induction, bortezomib randomisation | Chemotherapy + bortezomib | 555 | 89% | - | 0.531 | link |
| Chemotherapy alone | 542 | 91% | ||||
| Event-free survival from study entry, high allelic ratio FLT3-ITD (hazard for patients not given sorafenib against sorafenib cohorts 2 and 3) | Chemotherapy without sorafenib (comparator) | 76 | - | 2.37 (1.45 to 3.88) | - | link |
| Chemotherapy + sorafenib (cohorts 2 and 3) | 72 | - | ||||
| Relapse risk from complete remission, high allelic ratio FLT3-ITD (hazard for patients not given sorafenib) | Chemotherapy without sorafenib (comparator) | 76 | - | 3.03 (1.31 to 7.04) | 0.010 | link |
| Chemotherapy + sorafenib (cohorts 2 and 3) | 72 | - |
FLT3 inhibitors are now incorporated into frontline paediatric AML therapy for FLT3-ITD, with gilteritinib being studied in the successor trial.
Bortezomib should not be added to standard chemotherapy for childhood acute myeloid leukaemia; the trial's FLT3-ITD sorafenib cohorts were reported separately.
Similar pages
not linked directly; found by shared links- TrialAALL1521
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- TrialAALL1231
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- TrialMORPHO
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- TrialGRAALL-2005
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- TrialQUAZAR AML-001
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- TrialIntReALL SR 2010
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