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ALL R3 found, to the investigators' surprise, that using mitoxantrone instead of idarubicin in the first block of treatment for children whose leukaemia had relapsed nearly doubled the chance of being alive without progression three years later, and mitoxantrone-based reinduction became the standard.
ALL R3 was an open-label randomised trial in 22 centres in the United Kingdom and Ireland and nine in Australia and New Zealand for children with a first relapse of acute lymphoblastic leukaemia. Patients were stratified into high-, intermediate- and standard-risk groups by the duration of first remission, site of relapse and immunophenotype, and randomised to idarubicin or mitoxantrone during induction. After three treatment blocks, high-risk patients and intermediate-risk patients with high residual disease went to allogeneic transplant; the rest continued chemotherapy.
Of 239 registered patients, 216 were randomised. Three-year progression-free survival was 64.6 percent with mitoxantrone against 35.9 percent with idarubicin, and three-year overall survival 69.0 against 45.2 percent; the difference came from fewer disease events rather than fewer treatment deaths. The result was unexpected and the randomisation was stopped early. Mitoxantrone-based reinduction became the reference arm of later relapse trials including IntReALL, and the corpus's relapsed childhood leukaemia page names it as the reinduction backbone.
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.
216 randomised.
95% CI 54.2 to 73.2 · 95% CI 25.9 to 45.9
Source95% CI 58.5 to 77.3 · 95% CI 34.5 to 55.3
SourceNumbers not yet public.
Source| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Progression-free survival at 3 yearsprimary | Mitoxantrone reinduction | 103 | 64.6% | - | 0.0004 | link |
| Idarubicin reinduction | 109 | 35.9% | ||||
| Overall survival at 3 years | Mitoxantrone reinduction | 103 | 69% | - | 0.004 | link |
| Idarubicin reinduction | 109 | 45.2% | ||||
| Disease events (progression, second relapse, disease-related death), hazard for mitoxantrone against idarubicin | Mitoxantrone reinduction | 103 | - | 0.56 (0.34 to 0.92) | 0.007 | link |
| Idarubicin reinduction | 109 | - |
Shares Mitoxantrone, Relapsed and refractory acute lymphoblastic leukaemia in children, Leukaemia (all types), Acute lymphoblastic leukaemia and the tag soc-trials.
Shares Asparaginase (pegaspargase, calaspargase pegol, Erwinia asparaginase), Methotrexate, Dexamethasone, Leukaemia (all types) and the tag soc-trials.
Shares Asparaginase (pegaspargase, calaspargase pegol, Erwinia asparaginase), Dexamethasone, Leukaemia (all types), Acute lymphoblastic leukaemia and the tag soc-trials.
Shares Leukaemia (all types), Acute lymphoblastic leukaemia, Cytotoxic chemotherapy and the tag soc-trials.
Shares Leukaemia (all types), Acute lymphoblastic leukaemia, Cytotoxic chemotherapy and the tag soc-trials.
Shares Relapsed and refractory acute lymphoblastic leukaemia in children, Leukaemia (all types), Acute lymphoblastic leukaemia and the tag soc-trials.
Shares Leukaemia (all types), Acute lymphoblastic leukaemia, Cytotoxic chemotherapy and the tag soc-trials.
Shares Leukaemia (all types), MRD / molecular residual disease testing and the tag soc-trials.