ALL R3
Effect of mitoxantrone on outcome of children with first relapse of acute lymphoblastic leukaemia (ALL R3): an open-label randomised trial
N = 216NCT00967057
- Population
- Children aged 1 to 18 years with first relapse of acute lymphoblastic leukaemia; 216 randomly assigned
- Design
- Open-label randomized trial at 22 centres in the UK and Ireland and nine in Australia and New Zealand. Patients aged 1 to 18 years with first relapse were stratified into high-, intermediate- and standard-risk groups by duration of first complete remission, site of relapse and immunophenotype, and randomized to idarubicin or mitoxantrone in induction (stratified concealed randomization). After three blocks of therapy, high-risk patients and intermediate-risk patients with high post-induction minimal residual disease (at least 1 in 10,000 cells) received allogeneic stem-cell transplant. 239 patients were registered; 216 were randomly assigned (111 idarubicin, 105 mitoxantrone) and 212 were analysed (109 and 103); randomization stopped in December 2007. Registered as ISRCTN45724312 (printed ISCRTN in the paper; confirmed in the ISRCTN registry as ALLR3) and NCT00967057.
- Primary endpoint
- PFS
- Arms
- Idarubicin induction (control, n = 111): Idarubicin in induction (comparator; the paper describes mitoxantrone as the test drug)
- Mitoxantrone induction (experimental, n = 105): Mitoxantrone in induction
- People
- Parker C, senior author Saha V
Δ 36-month PFS+28.7 pointsΔ 36-month OS+23.8 points
Show the numbers
| Endpoint | Analysis | Mitoxantrone induction | Idarubicin induction | Effect |
|---|---|---|---|---|
| PFSRandomized patients analysed (109 idarubicin, 103 mitoxantrone)Progression-free survival (primary outcome; intention-to-treat analysis per the abstract) | primaryParker 2010 | 64.6% at 3 y (54.2–73.2%) | 35.9% at 3 y (25.9–45.9%) | P=0.0004Estimated 3-year PFS. Disease events (progression, second relapse, disease-related deaths): HR 0.56 (0.34 to 0.92), p=0.007; adverse treatment effects (treatment death, second malignancy): HR 0.52 (0.24 to 1.11), p=0.11. Randomization was stopped in December 2007 because of differences in PFS and overall survival. |
| OSRandomized patients analysed (109 idarubicin, 103 mitoxantrone) | primaryParker 2010 | 69% at 3 y (58.5–77.3%) | 45.2% at 3 y (34.5–55.3%) | P=0.004Estimated 3-year overall survival. |
| Endpoint | Analysis | Mitoxantrone induction | Idarubicin induction | Effect |
|---|---|---|---|---|
| PFSRandomized patients analysed (109 idarubicin, 103 mitoxantrone)Progression-free survival (primary outcome; intention-to-treat analysis per the abstract) | primaryParker 2010 | 64.6% at 3 y (54.2–73.2%) | 35.9% at 3 y (25.9–45.9%) | P=0.0004Estimated 3-year PFS. Disease events (progression, second relapse, disease-related deaths): HR 0.56 (0.34 to 0.92), p=0.007; adverse treatment effects (treatment death, second malignancy): HR 0.52 (0.24 to 1.11), p=0.11. Randomization was stopped in December 2007 because of differences in PFS and overall survival. |
| OSRandomized patients analysed (109 idarubicin, 103 mitoxantrone) | primaryParker 2010 | 69% at 3 y (58.5–77.3%) | 45.2% at 3 y (34.5–55.3%) | P=0.004Estimated 3-year overall survival. |