ALL R3 (UKALLR3)
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.
Overview
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.
- 64.6 vs 35.9 out of 100 alive without the cancer growing at 3 years with Mitoxantrone reinduction compared with Idarubicin reinduction; 28.7 more per 100.
- Roughly one extra person helped for every 3 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.
- The p-value (0.0004) says a difference this large would rarely happen by chance; it does not say how large or how useful the difference is.
- 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.
- 69 vs 45.2 out of 100 alive at 3 years with Mitoxantrone reinduction compared with Idarubicin reinduction; 23.8 more per 100.
- Roughly one extra person helped for every 4 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.
- The p-value (0.004) says a difference this large would rarely happen by chance; it does not say how large or how useful the difference is.
- Overall survival counts deaths from any cause, so it is the most direct measure of whether a treatment helps people live longer.
- The treated group had about 44 percent lower chance of the event at any given time (hazard ratio 0.56).
- The absolute difference, how many more people out of 100 were helped, is not reported here.
- This endpoint is not one of the standard survival or response measures; read it alongside the trial's primary result.
- These results apply to the people the trial enrolled: Children aged 1 to 18 with a first relapse of acute lymphoblastic leukaemia in the United Kingdom, Ireland, Australia and New Zealand: reinduction with idarubicin or mitoxantrone alongside dexamethasone, vincristine, asparaginase and methotrexate, with later therapy and transplant decided by risk group and measurable residual disease. People in a different situation may not see the same effect.
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 | - |
Similar pages
not linked directly; found by shared links- TrialIntReALL SR 2010
Shares Mitoxantrone, Leukaemia (all types), Relapsed and refractory acute lymphoblastic leukaemia in children, Acute lymphoblastic leukaemia and the tag soc-trials.
- TrialAALL0232
Shares Asparaginase (pegaspargase, calaspargase pegol, Erwinia asparaginase), Leukaemia (all types), Methotrexate, Dexamethasone and the tag soc-trials.
- TrialAALL1231
Shares Asparaginase (pegaspargase, calaspargase pegol, Erwinia asparaginase), Leukaemia (all types), Dexamethasone, Acute lymphoblastic leukaemia and the tag soc-trials.
- TrialGRAALL-2005
Shares Leukaemia (all types), Acute lymphoblastic leukaemia, Cytotoxic chemotherapy and the tag soc-trials.
- TrialAALL1521
Shares Leukaemia (all types), Acute lymphoblastic leukaemia, Cytotoxic chemotherapy and the tag soc-trials.
- TrialAALL1331
Shares Leukaemia (all types), Relapsed and refractory acute lymphoblastic leukaemia in children, Acute lymphoblastic leukaemia and the tag soc-trials.
- TrialEsPhALL (EsPhALL2004 and EsPhALL2010)
Shares Leukaemia (all types), Acute lymphoblastic leukaemia, Cytotoxic chemotherapy and the tag soc-trials.
- TrialMORPHO
Shares Leukaemia (all types), MRD / molecular residual disease testing and the tag soc-trials.