FORUM
Allogeneic Stem Cell Transplantation for Children and Adolescents With Acute Lymphoblastic Leukaemia
Phase 3N = 413NCT01949129
- Population
- Patients aged 18 years or younger at diagnosis and 4 to 21 years at transplant, in complete remission before transplant, with an HLA-compatible related or unrelated donor
- Design
- International, multicenter, open-label, randomized, noninferiority phase 3 study (FORUM). Myeloablative conditioning with fractionated 12 Gy total body irradiation (TBI) and etoposide versus fludarabine, thiotepa and either busulfan or treosulfan; noninferiority margin 8%. 543 patients were screened; the abstract reports 417 randomly assigned between April 2013 and December 2018, while the full-text Results report 413 randomly assigned between April 2013 and March 2019 (212 to TBI, 201 to chemoconditioning; random assignment errors excluded), the ITT population analysed here. The futility stopping rule, which halts random assignment if chemoconditioning is significantly inferior to TBI, was applied on 31 March 2019. Median follow-up 2.1 years. Patients were in complete remission before transplant (54% in first complete remission at inclusion), so the trial is not restricted to relapse.
- Primary endpoint
- OS
- Arms
- TBI plus etoposide (control, n = 212): Fractionated 12 Gy total body irradiation and etoposide
- Chemoconditioning (experimental, n = 201): Fludarabine, thiotepa and either busulfan or treosulfan
- People
- Peters C, senior author Bader P
Δ 24-month OS−16 pointsΔ 24-month Cumulative incidence of relapse+21 pointsΔ 24-month Treatment-related mortality+7 points
Show the numbers
| Endpoint | Analysis | Chemoconditioning | TBI plus etoposide | Effect |
|---|---|---|---|---|
| OSITT (212 TBI, 201 chemoconditioning) | interimmedian follow-up 2.1 yearsPeters 2021 | 75% at 2 y (67–81%) | 91% at 2 y (86–95%) | P<0.00012-year overall survival (primary end point). Printed as proportions 0.91 and 0.75; converted to percent. |
| Cumulative incidence of relapseITT (212 TBI, 201 chemoconditioning); the paper states results are from ITT analyses unless otherwise indicated | interimmedian follow-up 2.1 yearsPeters 2021 | 33% at 2 y (25–40%) | 12% at 2 y (8–17%) | P<0.00012-year cumulative incidence of relapse (secondary end point), printed as 0.12 and 0.33; converted to percent. |
| Treatment-related mortalityITT (212 TBI, 201 chemoconditioning); the paper states results are from ITT analyses unless otherwise indicated | interimmedian follow-up 2.1 yearsPeters 2021 | 9% at 2 y (5–14%) | 2% at 2 y | P=0.02692-year cumulative incidence, reported as 0.02 and 0.09. The TBI-arm 95% CI is printed as less than 0.01 to 0.05 and is not entered as an interval because the lower bound is not a number. |
| Endpoint | Analysis | Chemoconditioning | TBI plus etoposide | Effect |
|---|---|---|---|---|
| OSITT (212 TBI, 201 chemoconditioning) | interimmedian follow-up 2.1 yearsPeters 2021 | 75% at 2 y (67–81%) | 91% at 2 y (86–95%) | P<0.00012-year overall survival (primary end point). Printed as proportions 0.91 and 0.75; converted to percent. |
| Cumulative incidence of relapseITT (212 TBI, 201 chemoconditioning); the paper states results are from ITT analyses unless otherwise indicated | interimmedian follow-up 2.1 yearsPeters 2021 | 33% at 2 y (25–40%) | 12% at 2 y (8–17%) | P<0.00012-year cumulative incidence of relapse (secondary end point), printed as 0.12 and 0.33; converted to percent. |
| Treatment-related mortalityITT (212 TBI, 201 chemoconditioning); the paper states results are from ITT analyses unless otherwise indicated | interimmedian follow-up 2.1 yearsPeters 2021 | 9% at 2 y (5–14%) | 2% at 2 y | P=0.02692-year cumulative incidence, reported as 0.02 and 0.09. The TBI-arm 95% CI is printed as less than 0.01 to 0.05 and is not entered as an interval because the lower bound is not a number. |