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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.
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.
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.
Shares Children's Oncology Group (COG), Leukaemia (all types), Small-molecule kinase inhibitors, Cytotoxic chemotherapy and the tag soc-trials.
Shares FLT3-mutated acute myeloid leukaemia, Leukaemia (all types), Acute myeloid leukaemia, Small-molecule kinase inhibitors and the tag soc-trials.
Shares Bortezomib, Children's Oncology Group (COG), Leukaemia (all types), Cytotoxic chemotherapy and the tag soc-trials.
Shares Children's Oncology Group (COG), Leukaemia (all types), Cytotoxic chemotherapy and the tag soc-trials.
Shares Leukaemia (all types), Small-molecule kinase inhibitors, Cytotoxic chemotherapy and the tag soc-trials.
Shares Leukaemia (all types), Cytotoxic chemotherapy and the tag soc-trials.
Shares Leukaemia (all types), Acute myeloid leukaemia and the tag soc-trials.
Shares Leukaemia (all types), Cytotoxic chemotherapy and the tag soc-trials.