GRAALL-2005
GRAALL-2005 treated adults with acute lymphoblastic leukaemia using an intensive protocol borrowed from children's medicine and asked whether giving cyclophosphamide in a more intense split schedule helped; it did not, and the trial also showed that people aged 55 and over tolerate the paediatric-style treatment poorly.
Overview
GRAALL-2005 was the French, Belgian and Swiss GRAALL group's randomised phase 3 protocol for adults aged 18 to 59 with newly diagnosed acute lymphoblastic leukaemia. Patients were assigned by immunophenotype and genetics to three linked trials (T-cell or Philadelphia-negative B-cell disease, CD20-positive B-cell disease with or without rituximab, and Philadelphia-positive disease under GRAAPH-2005). The paediatric-inspired backbone came from the earlier GRAALL-2003 study. The randomised question reported in 2018 was whether hyperfractionated cyclophosphamide in first induction and late intensification improved outcomes.
Among 787 evaluable patients the complete remission rate was 91.9 percent, five-year event-free survival 52.2 percent and overall survival 58.5 percent. Hyperfractionated cyclophosphamide did not raise the remission rate or lengthen event-free or overall survival, except in the minority aged 55 and over, who otherwise tolerated the whole programme poorly. The protocol is one of the reference paediatric-inspired regimens for younger adults, alongside CALGB 10403 and UKALL.
- 52.2 out of 100 people free of a major event at 5 years with All evaluable patients on the paediatric-inspired protocol.
- There was no comparison group, so this number cannot tell you how much of the effect is due to the treatment.
- 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.
- 91.9 out of 100 people had no sign of cancer on scans or tests with All evaluable patients on the paediatric-inspired protocol.
- There was no comparison group, so this number cannot tell you how much of the effect is due to the treatment.
- 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.
- 58.5 out of 100 people alive at 5 years with All evaluable patients on the paediatric-inspired protocol.
- There was no comparison group, so this number cannot tell you how much of the effect is due to the treatment.
- Overall survival counts deaths from any cause, so it is the most direct measure of whether a treatment helps people live longer.
- 55.7 vs 25.8 out of 100 free of a major event at 5 years with Age under 55 compared with Age 55 and over; 29.9 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.
- Put another way, the treated group had about 116 percent higher chance of the event at any given time (hazard ratio 2.16).
- The p-value (<0.001) 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.
- These results apply to the people the trial enrolled: Adults aged 18 to 59 with newly diagnosed Philadelphia-negative acute lymphoblastic leukaemia treated with a paediatric-inspired protocol: standard-dose or hyperfractionated cyclophosphamide during induction and late intensification. 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.
1,080 enrolled.
95% CI 48.5 to 55.7; hyperfractionated cyclophosphamide did not change the rate
Source95% CI 54.8 to 61.9
Source| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Complete remission | All evaluable patients on the paediatric-inspired protocol | 787 | 91.9% | - | - | link |
| Event-free survival at 5 yearsprimary | All evaluable patients on the paediatric-inspired protocol | 787 | 52.2% | - | - | link |
| Overall survival at 5 years | All evaluable patients on the paediatric-inspired protocol | 787 | 58.5% | - | - | link |
| Event-free survival at 5 years by age | Age under 55 | - | 55.7% | 2.16 | <0.001 | link |
| Age 55 and over | - | 25.8% |
Similar pages
not linked directly; found by shared links- TrialAALL1521
Shares Leukaemia (all types), Acute lymphoblastic leukaemia, Cytotoxic chemotherapy and the tag soc-trials.
- TrialIntReALL SR 2010
Shares Leukaemia (all types), Acute lymphoblastic leukaemia, Cytotoxic chemotherapy and the tag soc-trials.
- TrialAALL1231
Shares Leukaemia (all types), Acute lymphoblastic leukaemia, Cytotoxic chemotherapy and the tag soc-trials.
- TrialAALL0232
Shares Leukaemia (all types), Acute lymphoblastic leukaemia, Cytotoxic chemotherapy and the tag soc-trials.
- TrialEsPhALL (EsPhALL2004 and EsPhALL2010)
Shares Leukaemia (all types), Acute lymphoblastic leukaemia, Cytotoxic chemotherapy and the tag soc-trials.
- TrialALL R3 (UKALLR3)
Shares Leukaemia (all types), Acute lymphoblastic leukaemia, Cytotoxic chemotherapy and the tag soc-trials.
- TrialAALL1331
Shares Leukaemia (all types), Acute lymphoblastic leukaemia and the tag soc-trials.
- TrialEuroNet-PHL-C2
Shares Cyclophosphamide, Cytotoxic chemotherapy and the tag soc-trials.